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Everything you need to know about Covid-19 vaccines

Hacker News - Thu Jul 22 04:04

Vaccines have been the success story of the COVID-19 pandemic, with three already approved for use in the UK, and promising late-stage trial results for a further two vaccines backed by the UK government.

This feature illustrates how each type of vaccine works, and brings together key data for pharmacists on the vaccines currently available, as well as those in the pipeline. It will be updated regularly to include the latest information.

Although data on vaccine efficacy are included, direct comparisons between vaccines are not possible owing to the trials using different endpoints and taking place at different times — when there were differing case rates and circulating variants.

Click on the following links to take you to the vaccines you want to learn more about:

mRNA vaccines: Pfizer/BioNTech; Moderna; CureVac

Adenoviral vector vaccines: University of Oxford/AstraZeneca; Janssen

Protein-based vaccines: Novavax; GSK/Sanofi

Inactivated whole virus vaccines: Valneva

mRNA vaccines

mRNA vaccines are made using a new technology, which — in the case of COVID-19 — uses a nanoparticle to deliver the genetic instructions for human cells to make the SARS-CoV-2 spike protein, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body (see Figure).

Pfizer/BioNTech (BNT162b2)

Is it approved in the UK?

Yes, it was authorised for temporary supply on 2 December 2020 and now has a conditional marketing authorisation.

How many doses have been ordered?

100 million.

What are the storage requirements?

  • Store between -80°C and -60°C. Shelf life is 6 months.
  • After thawing, undiluted vaccine can be stored for up to 31 days at 2–8°C, and up to 2 hours at temperatures up to 25°C.
  • Once diluted, store at between 2–25˚C and use within 6 hours.
  • Data support temperature excursion of -60°C to -15°C for up to 2 weeks, and vials that have been exposed to a single temperature excursion within these conditions can be returned to the recommended storage conditions. Unlike the European Medicines Agency and the US Food and Drug Administration, the Medicines and Healthcare products Regulatory Agency has not advised that the vaccine can be transported and stored at these higher temperatures.

What are the latest data on effectiveness?

Phase II/III study results, published on 31 December 2020, suggest that a two-dose regimen of BNT162b2 confers 94.6% protection against symptomatic COVID-19, at least 7 days following the second dose. One case of severe COVID-19 occurred in the vaccine group compared with 9 in the placebo group.

Since then, several ‘real-world’ studies have been published. Data from an observational study of 7,000 healthcare workers in Israel suggests that vaccine efficacy against symptomatic COVID-19 infection is 85% from 15–28 days after the first dose. And further data from Israel’s mass vaccination programme estimates vaccine efficacy at days 14 through 20 after the first dose, and at 7 or more days after the second dose as follows: for documented infection, 46% (95% confidence interval [CI] 40–51) and 92% (95% CI 88–95); for symptomatic COVID-19, 57% (95% CI 50–63) and 94% (95% CI 87–98); for hospitalisation, 74% (95% CI 56–86) and 87% (95% CI 55–100); and for severe disease, 62% (95% CI 39–80) and 92% (95% CI 75–100), respectively. Estimated effectiveness in preventing death from COVID-19 is 72% (95% CI 19–100) for days 14 through 20 after the first dose.

Further data from a national-level observational assessment of the vaccination programme in Israel, published in The Lancet on 5 May 2021, suggest that the vaccine is highly effective, providing 95.3% protection against infection and 96∙7% protection against death 7 days after the second dose. Protection against symptomatic and asymptomatic infection was 97.0% and 91.5%, respectively. The vaccine also provided 97.2% protection against hospitalisation overall and 97∙5% protection against severe and critical hospitalisation. The B.1.1.7 variant accounted for 94·5% of sequenced cases.

Early data from Public Health England’s (PHE’s) prospective SIREN study of healthcare workers, published as a pre-print on 22 February 2021, suggests vaccine efficacy of 72% (95% CI 58–86) against asymptomatic and symptomatic infection 21 days after the first dose and 86% (95% CI 76–97) 7 days after the second dose.

And observational data from a US study of healthcare personnel, first responders, and other essential and frontline workers, published by the Centers for Disease Control and Prevention (CDC) on 29 March 2021, suggest vaccine efficacy for mRNA vaccines (Pfizer/BioNTech and Moderna) is 80% (95% CI 59%–90%) against asymptomatic and symptomatic infection at least 14 days after the first dose and 90% (95% CI 68%–97%) at least 14 days after the second dose.

This high efficacy is sustained for at least six months, according to Pfizer/BioNTech, which announced an updated topline analysis of their phase III trial on 1 April 2021. The analysis suggests that the vaccine efficacy is 91.3% (95% CI 89.0–93.2) against COVID-19 up to six months after the second dose. The analysis also suggests vaccine efficacy is 100% (95% CI 88.0–100.0) and 95.3%  (95% CI 71.0–99.9) against severe disease, as defined by the CDC and the US Food and Drug Administration, respectively.

And preliminary data from a large UK surveillance study, published as a pre-print on 23 April 2021, suggest that infections fell by 65% (95% CI 60–70) after a first dose of the Pfizer/BioNTech or Oxford/AstraZeneca vaccines, and 70% (95% CI 62–77) after a second dose of the Pfizer/BioNTech vaccine.

A laboratory study, published as a pre-print on 17 May 2021 by University of Birmingham in collaboration with Public Health England on 14 May 2021, has found that extending the dosing interval from 3 to 12 weeks increased the peak SARS-CoV-2 spike specific antibody response 3.5-fold in 175 people aged over 80 years old. T cell responses were weaker when the second dose was delayed, but settled down to similar levels more than three months after the first dose was given.

A trial in adolescents has been published in The New England Journal of Medicine (27 May 2021), which found vaccine efficacy was 100% in over 2,000 participants aged 12 to 15 years old, with 18 cases in the placebo group and none in the vaccine group.

Data on under 40 year olds, published by PHE on 1 July 2021, suggest vaccine efficacy is 61% (95% CI 56–66%) after 1 dose.

Real-world data, released as a pre-print by Public Health England on 9 July 2021, show for the first time that most people who are clinically vulnerable to COVID-19 still receive high levels of protection after two doses of vaccine. Vaccine efficacy is estimated as approximately 60% after one dose of either Pfizer/BioNTech or Oxford/AstraZeneca, with little variation by age. After two doses, vaccine effectiveness is 88.5% (95% CI 81.5–92.9) with Pfizer/BioNTech in risk groups aged 65 and over. For those who are immunosuppressed, vaccine efficacy after a second dose is 74.1% (95% CI 48.8–87.0), with similar protection to those who are not in a risk group. This rises from 4.0% (95% CI -31.5–29.9) after a first dose.

Is it effective against new variants?

Yes, but effectiveness may be reduced against some variants and more data are needed.

Alpha (B.1.1.7; first detected in UK): A small laboratory study using vaccine sera suggests roughly equivalent neutralisation of  this variant. And data from the UK vaccination programme, published as pre-prints on 1 March 2021 and 23 April 2021, and the PHE SIREN study, suggest vaccine efficacy is still high against Alpha.

Observational data from the vaccine roll-out in Qatar, where 265,410 people have received two doses of the Pfizer/BioNTech vaccine, published in a letter to The New England Journal of Medicine on 5 May 2021, suggest vaccine efficacy is 89.5% (95% CI 85.9–92.3) at 14 or more days after the second dose. Vaccine efficacy against severe, critical, or fatal disease caused by either Alpha or Beta was high at 97.4% (95% CI 92.2–99.5).

And national-level data from Israel’s vaccination programme confirm that the vaccine is highly effective against the Alpha variant (see above).

Beta (B.1.351, first detected in South Africa): A small laboratory study using vaccine sera suggests a 10.3-fold reduction in antibodies that neutralise this variant. However, analysis of 800 participants in Pfizer/BioNTech’s phase III trial, announced by the companies on 1 April 2021, shows nine cases of COVID-19 in the placebo group, six of which were due to Beta, and none in the vaccine group, suggesting vaccine efficacy of 100% (95% CI 53.5–100.0).

Observational data from the vaccine roll-out in Qatar, where 265,410 people have received two doses of the Pfizer/BioNTech vaccine, published in a letter to The New England Journal of Medicine on 5 May 2021, suggest vaccine efficacy is 75.0% (95% CI 70.5–78.9). Vaccine efficacy against severe, critical, or fatal disease caused by either Alpha or Beta was high at 97.4% (95% CI 92.2–99.5).

Gamma (P1, first detected in Japan/Brazil): A small laboratory study using vaccine sera suggests roughly equivalent neutralisation of this variant, although two other laboratory studies, published as preprints, suggest antibody titres were reduced by 2.6-fold and 14-fold. The impact is yet to be confirmed in clinical trials.  

Delta (B.1.617.2, first detected in India): A study using vaccine sera from 250 participants after two doses, published in The Lancet on 3 June 2021, suggests neutralising antibody titres against the Delta variant are reduced 5.8-fold compared with wild-type virus but are still able to neutralise the virus to some extent.

An observational study carried out by PHE, published as a pre-print on 22 May 2021, which included 1,054 people confirmed as having the B.1.617.2 variant, suggested the Pfizer/BioNTech vaccine has an efficacy of 87.9% (95% CI 78.2–93.2) against symptomatic disease from the B.1.617.2 variant 2 weeks after the second dose, compared with 93.4% (95% CI 90.4–95.5) against the B.1.1.7 variant. Vaccine efficacy after one dose was 33.2% (95% CI 8.3–51.4) against the B.1.617.2 variant compared with 49.2% (95% CI 42.6–55.0) against the B.1.1.7 variant.

An updated analysis, including 14,019 symptomatic cases infected with the delta variant, was published as a pre-print by PHE on 14 June 2021. The analysis suggests vaccine efficacy against admission to hospital with the delta variant is 94% (95% CI 46–99) after one dose and 96% (95% CI 86–99) after two doses.

A Scottish study published on 14 June 2021 as a research letter in The Lancet, included 19,543 cases (7,723 with the Delta variant), of whom 377 were admitted to hospital (134 with the Delta variant). The vaccine offered 79% (955 CI 75–82) protection against the Delta variant and 92% (95% CI 90–93)  against the Alpha variant.

Does it work in older people?

Yes.

Data from the UK vaccination programme suggest vaccine efficacy in those aged ≥70 years reached 58% (95% CI 49–65) from 28 days after vaccination, before plateauing.

Individuals who receive one dose have an additional 42% (95% CI 32–51) lower risk of emergency hospitalisation, and an additional 54% (95% CI 41–64) lower risk of death, making a single dose of the vaccine 80% effective at preventing hospitalisation.

In a study published as a pre-print on 1 March 2021, vaccine efficacy in those aged ≥80 years was 59% (95% CI 46–68) from 28–34 days after the first dose, then plateaued, before rising to 85% (95% CI 79–89) from 14 days after the second dose.

Data from the mass vaccination programme in Israel also confirms that vaccine efficacy is similar in those aged >70 years, and in younger age groups, after the second dose. Further data from a national-level observational assessment of the vaccination programme in Israel, published in The Lancet on 5 May 2021, suggest that people over 85 years had 94.1% protection against infection, 96.9% against hospitalisation, and 97% against death 7 days after receiving their second dose.

Further observational data from PHE, published as a pre-print on 10 May 2021, suggest that a single dose of the Pfizer/BioNTech vaccine reduces risk of death in over 70-year-olds by 44% (0.56, 95% CI 0.47–0.68), and two doses reduce the risk by 69% (0.31, 95% CI 0.14-0.69), compared with unvaccinated cases, which, when combined with the protection vaccines offer against becoming a case in the first place, is equivalent to approximately 80% protection against death with one dose and 97% protection with two doses. Another preprint, published by PHE on the same date, suggests, for the over 80s, two doses of the Pfizer/BioNTech vaccine reduce the risk of hospitalisation by 93% (95% CI 89–95). In 70- to 79-year-olds, one dose reduces the risk of hospitalisation by 81% (95% CI 73–87).

A large prospective cohort study (VIVALDI) of vaccine efficacy in 10,412 residents of long-term care facilities in England, all aged 65 years and older, was published in The Lancet Infectious Diseases on 23 June 2021. Vaccine efficacy for a single dose of either the Pfizer/BioNTech or Oxford/AstraZeneca vaccines was estimated to be 56% (95% CI 19–76) at 28–34 days, and 62% (23–81) at 35–48 days post-vaccination. Similar effect sizes at 35-48 days were seen for the Pfizer/BioNTech vaccine (65% reduced risk) and Oxford/AstraZeneca vaccine (68% reduced risk).

Does it reduce transmission?

Yes.

Data from Israel, published in a pre-print on 8 February 2021, suggest that infections occurring 12 days or longer following vaccination have significantly reduced viral loads, potentially affecting viral shedding and contagiousness as well as severity of the disease.

Results from the SIREN study, conducted among healthcare workers in England and published in a pre-print in The Lancet on 22 February 2021, suggest vaccine efficacy against both symptomatic and asymptomatic infections is 72% after one dose and 86% after two doses. And preliminary data from a large UK surveillance study, published as a preprint on 23 April 2021, suggest symptomatic infections fell by 72% (69% to 74%), and asymptomatic infections fell by 57% (64% to 47%) after one dose of the Pfizer/BioNTech or Oxford/AstraZeneca vaccines. 

A UK study of healthcare workers at Cambridge University Hospitals NHS Foundation Trust, published as a pre-print on 24 February 2021, found a four-fold decrease in the risk of asymptomatic infection among healthcare workers ≥12 days post-vaccination, compared with unvaccinated healthcare workers.

And a study led by Public Health Scotland and the University of Glasgow, published as a pre-print on 12 March 2021, examining infections in nearly 150,000 vaccinated and unvaccinated healthcare workers and 200,000 of their household members, provides the first direct evidence of a reduction in transmission. There was a 30% reduction in documented cases of infection in household members of vaccinated compared with unvaccinated healthcare workers (hazard ratio [HR] 0.70, 95% CI 0.63–0.78), which the researchers estimate translates to a 60% reduction in transmission since household members could be infected by other routes. A 54% reduction in documented cases in household members was observed ≥14 days after the second dose (HR 0.46, 95% CI 0.30—0.70). Participants received either the Pfizer/BioNTech vaccine or the Oxford/AstraZeneca vaccine.

The results of the Scottish research are backed up by a Public Health England study, published on 28 April 2021, which found that individuals who become infected 3 weeks after receiving one dose of the Pfizer/BioNTech or Oxford/AstraZeneca vaccine are between 38% and 49% less likely to pass the virus on to their household contacts than those who were unvaccinated. The study included over 57,000 contacts from 24,000 households in which there was a lab-confirmed case that had received a vaccination, compared with nearly 1 million contacts of unvaccinated cases.

Are there any safety concerns?

The safety profile reflects that seen in clinical trials (injection-site reactions and generalised ‘flu-like’ symptoms).

On 7 May 2021, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency announced that it had concluded a review of a safety signal for facial swelling in people with a history of injections with dermal fillers, and found that there is at least a reasonable possibility of a causal association between the vaccine and the reported cases and requested that it should be added as a side effect in the summary of product characteristics. The PRAC stressed that the risk-benefit balance of the vaccine remains unchanged.

On 25 Jun 20201, the product information was updated to include a warning that there have been very rare reports of myocarditis and pericarditis occurring after vaccination, often in younger men and shortly after the second dose of the vaccine. As of 7 July 2021, the Medicines and Healthcare products Regulatory Agency had received 81 reports of myocarditis and 63 reports of pericarditis following use of the Pfizer/BioNTech vaccine.

Cases are typically mild and individuals tend to recover within a short time following standard treatment and rest. However, healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. Vaccinated individuals should also seek immediate medical attention should they experience new onset of chest pain, shortness of breath, palpitations or arrhythmias.

Full product information can be viewed here.

Moderna (mRNA-1273)

Is it approved in the UK?

Yes, it was authorised for temporary supply on 3 January 2021, and given a conditional marketing authorisation on 1 April 2021.

How many doses have been ordered?

17 million.

What are the storage requirements?

  • Store between -25º and -15ºC. Shelf life is 7 months.
  • Once thawed, unopened vials can be stored at 2–8 °C for up to 30 days or at 8– 25°C for 12 hours.
  • After opening, store at 2–25˚C and use within 6 hours.

What are the latest data on effectiveness?

Vaccine efficacy was 94.1% (95% CI 89.3–96.8) against symptomatic infection 14 days after the second dose in clinical trials. No cases of severe COVID-19 occurred in the vaccine group compared with 30 in the placebo group.

Observational data from a US study of healthcare personnel, first responders, and other essential and frontline workers, published by the Centers for Disease Control and Prevention on 29 March 2021, suggest vaccine efficacy for mRNA vaccines (Pfizer/BioNTech and Moderna) is 80% against asymptomatic and symptomatic infection at least 14 days after the first dose and 90% at least 14 days after the second dose.

The high efficacy is sustained for six months, according to updated results from the phase III COVE study announced by Moderna on 13 April 2021. A review of cases suggests vaccine efficacy starting two weeks following the second dose is greater than 90% against all cases of COVID-19, and greater than 95% against severe cases of COVID-19, with a median follow up of approximately six months following the second dose.

Moderna has also announced topline results from a phase II/III trial in adolescents (25 May 2021), which found that vaccine efficacy was 100% in 3,732 participants aged 12 to 17 years old, with 4 cases in the placebo group and none in the vaccine group at least 14 days after the second dose.

Data on under 40 year olds, published by PHE on 1 July 2021, suggest vaccine efficacy is 72% (95% CI 46–86%) after 1 dose.

Does it work against new variants?

Yes, but effectiveness may be reduced against some variants and more data are needed.

Alpha (B.1.1.7; first detected in UK): A small laboratory study suggest no significant difference, but this is yet to be demonstrated in clinical trials.

Beta (B.1.351, first detected in South Africa): A small laboratory study suggest a 6.5-fold reduction in antibodies that neutralise this variant, but this is yet to be demonstrated in clinical trials.

Gamma (P1, first detected in Japan/Brazil): A small laboratory study suggests antibody titres are reduced by 2.6-fold. The impact is yet to be confirmed in clinical trials.

Delta (B.1.617.2, first detected in India): A small laboratory study, published as a pre-print on 28 June 2021, suggests neutralising antibody titres are produced against the Delta variant one week after the second dose but they are reduced by 2.1-fold compared with the ancestral strain. The impact is yet to be confirmed in clinical trials.

Does it work in older people?

Yes, in clinical trials.

In clinical trials, vaccine efficacy was 86.4% (95% CI 61.4–95.2) against symptomatic infection 14 days after the second dose in those aged >65 years.

Does it reduce transmission?

More than likely, but we need more data.

Data from swabs taken during clinical trials to check for asymptomatic infections, submitted to the US Food and Drug Administration by Moderna, suggest transmission could be reduced by two-thirds after one dose, but the number of asymptomatic infections was small and the data have not yet been peer reviewed.

An observational study in the US, published on 29 March 2021, also confirmed that both asymptomatic and symptomatic infections are reduced by 90% at least 14 days after the second dose.

Are there any safety concerns?

The safety profile reflects that seen in clinical trials (injection-site reactions and generalised ‘flu-like’ symptoms).

On 25 Jun 20201, the product information was updated to include a warning that there have been very rare reports of myocarditis and pericarditis occurring after vaccination, often in younger men and shortly after the second dose of the vaccine. As of 7 July 2021, the Medicines and Healthcare products Regulatory Agency had received 9 reports of myocarditis and 9 report of pericarditis following use of the Moderna vaccine.

Cases are typically mild and individuals tend to recover within a short time following standard treatment and rest. However, healthcare professionals should be alert to the signs and symptoms of myocarditis and pericarditis. Vaccinated individuals should also seek immediate medical attention should they experience new onset of chest pain, shortness of breath, palpitations or arrhythmias.

Full product information can be viewed here.

CureVac (CVnCoV and CV2CoV)

Is it approved in the UK?

No.

How many doses have been ordered/pre-ordered?

50 million.

What are the storage requirements?

  • Store at 2–8ºC for up to 3 months.
  • Store at room temperature for up to 24 hours.

What are the latest data on effectiveness?

In a phase 1 trial of CVnCoV, which is being co-developed by CureVac and Bayer, published as a preprint on 9 November 2020, antibody responses in vaccinated participants were comparable to the antibody response detected in recovered COVID-19 patients.

Interim analysis of a phase IIb/III study, which included 40,000 participants in 10 countries in Latin America and Europe, indicated that CVnCoV showed a vaccine efficacy of 47% against COVID-19 disease of any severity at least two weeks after the second dose. More than half of 124 cases (57%) sequenced were caused by variants of concern, with most of the remaining cases caused by other less characterised variants.

A pre-clinical trial of CV2CoV, a second generation vaccine being co-developed by CureVac and GSK for enhanced protein expression and immunogenicity, published as a pre-print on 13 May 2021, showed it induced high levels of antigen production as well as strong and dose-dependent immune responses in vaccinated animals. 

Does it work against new variants?

We don’t know yet.

Alpha (B.1.1.7; first detected in UK): In a laboratory study, the serum of animals vaccinated with CV2CoV showed significant cross-neutralisation against Alpha variants.

Beta (B.1.351, first detected in South Africa): In a laboratory study, the serum of animals vaccinated with CV2CoV showed significant cross-neutralisation against Beta variants.

Gamma (P1, first detected in Japan/Brazil): No evidence yet.

Delta (B.1.617.2, first detected in India): No evidence yet.

Does it work in older adults?

We don’t know yet.

Data not yet available.

Does it reduce transmission?

We don’t know yet.

Data not yet available.

Are there any safety concerns?

Phase I trial results for CVnCoV, published as a preprint on 20 November 2020, suggest the vaccine is well tolerated with no safety concerns identified.

Full product information is not yet available.

Adenoviral vector vaccines

Adenoviral vector vaccines are made using a relatively new technology, which uses a common cold virus to deliver the genetic instructions for human cells to make the SARS-CoV-2 spike protein, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body (see Figure).

Oxford/AstraZeneca (ChAdOx1 nCoV-19 [AZD1222], brand name Vaxzevria)

Is it approved in the UK?

Yes, it was authorised for temporary supply on 30 December 2020 and now has a conditional marketing authorisation.

How many doses have been ordered?

100 million.

What are the storage requirements?

  • Store at 2–8ºC. Shelf life is 6 months.
  • After opening, store at 2–25˚C and use within 6 hours.

What are the latest data on effectiveness?

Data released as a pre-print in The Lancet on 2 February 2021 suggest vaccine efficacy against symptomatic infection is 76% (95% CI 59–86) after a single dose in individuals aged 18–55 years, increasing to 82.4% (95% CI 62.7–91.7) after a second dose administered 12+ weeks later. There were no hospitalisations or deaths in the vaccine group.

AstraZeneca announced results of a study in 32,449 participants in the US, Peru and Chile on 25 March 2021, which suggests vaccine efficacy is 76% (95% CI 68–82) against symptomatic disease, and 100% against severe or critical disease and hospitalisation when two doses are given four weeks apart.

Preliminary data from a large UK surveillance study, published as a preprint on 23 April 2021, suggest that infections fell by 65% (95% CI 60–70) after a first dose of the Oxford/AstraZeneca or Pfizer/BioNTech vaccines.

Data published by PHE on 1 July 2021 suggest that two doses of the Oxford/AstraZeneca vaccine are estimated to provide 94% (95% CI 80–98) protection against death from COVID-19 in people aged 65 and over.

A study, published as a pre-print on 28 June 2021, suggests that a longer delay before the second dose of the vaccine (of 44 to 46 weeks) leads to an increased antibody titre after the second dose. A third “booster” dose, given 44 to 45 weeks after the second dose, induces antibodies to a level that correlate with high efficacy after second dose and boosts T-cell responses.

Real-world data, released as a pre-print by Public Health England on 9 July 2021, show for the first time that most people who are clinically vulnerable to COVID-19 still receive high levels of protection after two doses of vaccine. Vaccine efficacy is estimated as approximately 60% after one dose of either Oxford/AstraZeneca or Pfizer/BioNTech, with little variation by age. After two doses, vaccine effectiveness is 80.6% (95% CI 67.7–88.3%) for Oxford/AstraZeneca in risk groups aged 16 to 64 years old, and 79.7% (955 CI 61.6–89.3) in risk groups aged 65 and over. For those who are immunosuppressed, vaccine efficacy after a second dose is 74.1% (95% CI 48.8–87.0), with similar protection to those who are not in a risk group. This rises from 4.0% (95% CI -31.5–29.9) after a first dose.

Does it work against new variants?

Yes and no.

Alpha (B.1.1.7; first detected in UK): Real-world data from the UK vaccination programme, published as pre-prints on 1 March 2021 and 23 April 2021, suggest there is high vaccine efficacy against the UK variant. And study data published in The Lancet on 30 March 2021 show that, although neutralising antibody titres generated by the vaccine were nine-fold lower for the UK variant, vaccine efficacy against symptomatic cases was similar for Alpha and non-Alpha lineages (70.4% [95% CI 43·6–84·5] and 80.5% [95% CI 67·9–89·4], respectively).

Beta (B.1.351, first detected in South Africa): A small laboratory study using vaccine sera suggests a 12.4-fold reduction in antibodies that neutralise this variant. A study published in The New England Journal of Medicine on 16 March 2021 suggests that a two-dose regimen has an efficacy of only 10.4% (95% CI −76.8 to 54.8) against mild to moderate COVID-19 infection in almost 1,500 HIV-negative young adults. Efficacy against severe COVID-19 infection from this variant was not assessed.

Gamma (P1, first detected in Japan/Brazil): A small laboratory study using vaccine sera suggests antibody titres were reduced by 2.9-fold against this variant.

Delta (B.1.617.2, first detected in India): An observational study carried out by PHE and published as a pre-print on 22 May 2021, which included 1,054 people confirmed as having the Delta variant, suggested the Oxford/AstraZeneca vaccine has an efficacy of 59.8% (95% CI 28.9–77.3) against symptomatic disease from the Delta variant 2 weeks after the second dose, compared with 66.1% (95% CI 54.0–75.0) against the Alpha variant. Vaccine efficacy after one dose was 32.9% (95% CI 19.3–44.3) against the Delta variant compared with 51.4% (95% CI 47.3–55.2) against the Alpha variant.

An updated analysis, including 14,019 symptomatic cases infected with the Delta variant, was published as a pre-print by PHE on 14 June 2021. The analysis suggests vaccine efficacy against admission to hospital with the delta variant is 71% (95% CI 51–83) after one dose and 92% (95% CI 75–97) after two doses.

A Scottish study published on 14 June 2021 as a research letter in The Lancet, included 19,543 cases (7,723 with the Delta variant), of whom 377 were admitted to hospital (134 with the Delta variant). The vaccine offered 60% (95% CI 53–66) protection against the Delta variant and 73% (95% CI 66–78) against the Alpha variant.

Does it work in older people?

Yes.

Data from the UK vaccination programme, published on 17 March 2021, suggest vaccine efficacy in those aged ≥70 years is 56% (95% CI 43–65) from 28–34 days after receiving the vaccine, and increases to 58% (95% CI 38–72) from day 35 onwards. Individuals who received one dose had an additional 35% (95% CI 4–56) lower risk of emergency hospitalisation, making one dose of vaccine approximately 80% effective at preventing hospitalisation. There was insufficient follow-up to assess the vaccine’s effect on deaths.

Results of the US study confirm this, with a vaccine efficacy of 85% (95% CI 58–95) in those aged >65 years after two doses, four weeks apart.

Further observational data from PHE, published as a preprint on 10 May 2021, suggests that a single dose of the Oxford/AstraZeneca vaccine reduces risk of death in over 70-year-olds by 55% (0.45, 95% CI 0.34–0.59), compared with unvaccinated cases, which, when combined with the protection vaccines offer against becoming a case in the first place, is equivalent to approximately 80% protection against death. Another preprint, published by PHE on the same date, suggests, for the over 80s, one dose of the Oxford/AstraZeneca vaccine reduces the risk of hospitalisation by 73% (95% CI 60–81). In 70- to 79-year-olds, one dose reduces the risk of hospitalisation by 84% (95% CI 74–89).

A large prospective cohort study (VIVALDI) of vaccine efficacy in 10,412 residents of long-term care facilities in England, all aged 65 years and older, was published in The Lancet Infectious Diseases on 23 June 2021. Vaccine efficacy for a single dose of either the Pfizer/BioNTech or Oxford/AstraZeneca vaccines was estimated to be 56% (95% CI 19–76) at 28–34 days, and 62% (23–81) at 35–48 days post-vaccination. Similar effect sizes at 35-48 days were seen for the Pfizer/BioNTech vaccine (65% reduced risk) and Oxford/AstraZeneca vaccine (68% reduced risk).

Does it reduce transmission?

Yes.

Data released as a pre-print in The Lancet on 2 February 2021, which looked at the number of symptomatic and asymptomatic cases, suggest it could reduce transmission by 67%. However, a study published in The Lancet on 30 March 2021, found that vaccine efficacy against asymptomatic cases of the B.1.1.7 variant was only 28·9% (95% CI −77·1–71·4) compared with 69·7% (95% CI 33·0–86·3) for non-B.1.1.7 infections, although fewer cases were available for analysis, so confidence intervals were wide and overlapping. 

Preliminary data from a large UK surveillance study, published as a preprint on 23 April 2021, suggest that symptomatic infections fell by 72% (69% to 74%), and asymptomatic infections fell by 57% (64% to 47%) after one dose of the Pfizer/BioNTech or Oxford/AstraZeneca vaccines.

A study led by Public Health Scotland and the University of Glasgow, published as a pre-print on 12 March 2021 and examining infections in nearly 150,000 vaccinated and unvaccinated healthcare workers and 200,000 of their household members, provides the first direct evidence of a reduction in transmission. There was a 30% reduction in documented cases of infection in household members of vaccinated compared with unvaccinated healthcare workers (HR 0.70, 95% CI 0.63–0.78), which the researchers estimate translates to a 60% reduction in transmission since household members could be infected by other routes. A 54% reduction in documented cases in household members was observed ≥14 days after the second dose (HR 0.46, 95% CI 0.30—0.70). Participants received either the Pfizer/BioNTech vaccine or the Oxford/AstraZeneca vaccine.

The results of the Scottish research are backed up by a Public Health England study, published on 28 April 2021, which was carried out in a larger and wider cross-section of the population. The study found that individuals who become infected 3 weeks after receiving one dose of the Oxford/AstraZeneca or Pfizer/BioNTech vaccine are between 38% and 49% less likely to pass the virus on to their household contacts than those who were unvaccinated. The study included over 57,000 contacts from 24,000 households in which there was a lab-confirmed case that had received a vaccination, compared with nearly 1 million contacts of unvaccinated cases.

Are there any safety concerns?

The safety profile generally reflects that seen in clinical trials (injection-site reactions and generalised ‘flu-like’ symptoms).

However, on 7 April 2021, a rigorous safety review by the Medicines and Healthcare products Regulatory Agency (MHRA) of 79 UK reports of blood clotting cases alongside low levels of platelets following use of the Oxford/AstraZeneca vaccine for 20.2 million doses, concluded that evidence of a link between the vaccine and this extremely rare adverse event is getting stronger, although more work is still needed.

The Joint Committee on Vaccination and Immunisation (JCVI) advised that any remaining unvaccinated adults in phases 1 and 2 of the programme who are aged 18 to 29 years old and do not have an underlying health condition that puts them at higher risk from serious COVID-19, should be offered an alternative vaccine, if available. The JCVI explained that, given the very low numbers of events reported overall, there is currently a high level of uncertainty in estimates of the incidence of this adverse event by age group. However, the available data suggest a slightly higher incidence reported in younger adults, who are also at lowest risk of serious COVID-19. The benefits of prompt vaccination with the Oxford/AstraZeneca vaccine far outweigh the risk of adverse events for individuals 30 years and over and those who have underlying health conditions which put them at higher risk of severe COVID-19, it added.

On 7 May 2021, the JCVI extended its advice to the 30- to 39-year-old age group, recommending that unvaccinated adults aged 18–39 years with no underlying health conditions in the UK should be offered an alternative to the Oxford/AstraZeneca vaccine if available and where no substantial delay or barrier in access to vaccination would arise. The advice is based on falling case numbers changing the balance of risks and benefits, and the availability of alternatives to the Oxford/AstraZeneca vaccine.

The MHRA advises careful consideration before administering the vaccine to people at higher risk of blood clots because of a medical condition, and that a second dose should not be given to those who experienced this adverse event after the first dose. Vaccine recipients should also be advised to look out for symptoms four days or more after vaccination, including new onset of severe or persistent headache, blurred vision, confusion or seizures, shortness of breath, chest pain, leg swelling or persistent abdominal pain, and unusual skin bruising or pinpoint round spots beyond the injection site.

As of 7 July 2021, the MHRA had received Yellow Card reports of 405 cases of blood clots with low platelets following the vaccine, with a case fatality rate of 18%. The estimated number of first doses administered in the UK by 30 June 2021 was 24.6 million, giving an overall case incidence of 14.8 per million doses.

On 11 June 2021, the European Medicines Agency announced that its safety committee has concluded that people who have previously had capillary leak syndrome must not be vaccinated with the Oxford/AstraZeneca vaccine and that capillary leak syndrome should be added to the product information as a new side effect of the vaccine. The Medicines and Healthcare products Regulatory Agency said that it has received 8 reports of capillary leak syndrome in the context of more than 40 million doses of the vaccine given, and the current evidence does not suggest that the syndrome is caused by the vaccine. However, the MHRA is carefully considering whether or not precautionary advice is warranted for patients who have previously experienced capillary leak syndrome. On 16 July 2021, the MHRA added previous episodes of capillary leak syndrome as a contraindication.

Full product information can be viewed here.

Janssen (Ad26.COV2.S)

Is it approved in the UK?

Yes, it was granted a conditional marketing authorisation on 28 May 2021.

How many doses have been ordered?

30 million.

What are the storage requirements?

Store at -20ºC for 2 years or 2–8ºC for 3 months.

What are the latest data on effectiveness?

Results from a phase III trial published in The New England Journal of Medicine on 21 April 2021 suggest vaccine efficacy is 66.1% (95% CI 55.01; 74.80) overall against moderate to severe/critical disease (72.0% [95% CI 58.2–81.7] in the United States) 28 days after vaccination. It was 85.4% (95% CI 54.15–96.90) effective in preventing severe/critical disease. Vaccine efficacy against COVID-19 requiring medical intervention (defined as hospitalisation, intensive care unit admission, mechanical ventilation, extracorporeal membrane oxygenation) was 100.0% (95% CI 74.3–100.0) at least 28 days after vaccination.

In a letter to the editor, published in The New England Journal of Medicine on 14 July 2021, data from a small number of individuals suggests that the vaccine elicited durable humoral and cellular immune responses with minimal decreases for at least 8 months after immunisation.

Does it work against new variants?

Yes, although more data are needed.

Alpha (B.1.1.7; first detected in UK): A real-world study, published as a pre-print on 30 April 2021 and conducted in the US when Alpha was the predominant variant circulating, suggests that, among 1,779 vaccinated individuals matched with 17,744 unvaccinated controls, vaccine effectiveness against SARS-CoV-2 infection was 76.7% (95% CI 30.3–95.3) two weeks after vaccination.

Beta (B.1.351, first detected in South Africa): Phase III trial data suggest vaccine efficacy is 64.0% (95% CI 41.2–78.7) against moderate to severe/critical disease, and 81.7% (95% CI 46.2–95.4) against severe/critical disease.

Gamma (P1, first detected in Japan/Brazil): Phase III trial data suggest vaccine efficacy is 68.1% (95% CI 48.8–80.7) against moderate to severe/critical disease and 87.6% (95% CI 7.8–99.7) against severe/critical disease, although Gamma was detected in 30.6% of sequences and P2 was detected in 69.4% of sequences.

Delta (B.1.617.2, first detected in India): A small laboratory study, published as a pre-print on 1 July 2021, using vaccine sera from eight participants suggests neutralising antibody titres against the Delta variant are reduced 1.6-fold compared with the B1 strain. However, a different laboratory study, published as a pre-print on 19 July 2021, showed a more pronounced reduction in neutralising antibody titres of 5.5-fold.

Data in a letter to the editor, published in The New England Journal of Medicine on 14 July 2021, reveal an expansion of neutralising antibodies against the Delta variant over eight months, which the company says suggests maturation of B-cell responses even without further boosting.

Does it work in older adults?

Yes, although more data are needed.

Phase III trial data suggest a vaccine efficacy of 67.9% (95% CI 38.2–82.8) 28 days after vaccination in participants aged ≥60 years, although participants aged ≥60 years without comorbidities had a higher vaccine efficacy estimate than participants aged ≥60 years with comorbidities. Further follow-up data are needed to help understand these potential differences.

Does it reduce transmission?

Probably, but we need more data.

Phase III trial data show the vaccine reduced the risk of infection in a subgroup of 2,650 participants by 65.5% (95% CI 39.91–81.08), suggesting an impact on transmission, but this finding needs to be further investigated with additional data.

Are there any safety concerns?

The safety profile in clinical trials includes injection-site reactions and generalised ‘flu-like’ symptoms.

Administration of the Janssen vaccine in the US was temporarily paused on 13 April 2021 while the US Food and Drug Administration (FDA) and the Centers for Disease Control and Prevention (CDC) review data on six reported cases of blood clots with low platelets after receiving the vaccine among more than 6.8 million doses administered. Use of the vaccine resumed on the recommendation of the FDA and CDC on 24 April 2021, which said that a warning should now be included on the vaccine label about an elevated, but rare, risk of blood clots with low platelets. As of 12 May 2021, the CDC had identified 28 cases of blood clots with low platelets among more than 8.7 million people vaccinated.

The European Medicines Agency (EMA) has also reviewed four cases of blood clots and low platelets among vaccine recipients in clinical trials and the US vaccination programme. On 20 April 2021, the EMA concluded that the overall benefit/risk ratio for the vaccine remains positive but said that a warning about unusual blood clots with low platelets should be added to the product information and that these events should be listed as very rare side effects of the vaccine.

On 9 July 2021, the European Medicines Agency announced that its safety committee has concluded that people who have previously had capillary leak syndrome must not be vaccinated with the Janssen vaccine and that capillary leak syndrome should be added to the product information as a new side effect of the vaccine.

Full product information can be viewed here.

Protein-based vaccines

Protein-based vaccines are made using an older technology, which delivers SARS-CoV-2 spike proteins directly into the body, along with an adjuvant, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body (see Figure).

Novavax (NVX-CoV2373)

Is it approved in the UK?

No.

How many doses have been ordered/pre-ordered?

60 million.

What are the storage requirements?

Store at 2–8 ºC.

What are the latest data on effectiveness?

Data from a final analysis of a phase III UK trial involving more than 15,000 participants, announced by Novavax on 15 March 2021, suggest vaccine efficacy is 89.7% (95% CI 80.2–94.6) against symptomatic infection at least seven days after the second dose. No severe cases occurred in the vaccine group compared with five in the placebo group. The study was published in The New England Journal of Medicine on 30 June 2021.

Novavax announced preliminary data from a phase III trial of its vaccine in almost 30,000 participants in Mexico and the US on 14 June 2021. The study found that the vaccine demonstrated 90.4% efficacy overall (95% CI 82.9–94.6), with 63 mild cases in the placebo group and 14 mild cases in the vaccine group. Protection was 100% (95% CI 87.0–100) against moderate and severe disease, with ten moderate cases and four severe cases, all in the placebo group. Efficacy against variants of concern/interest was 93.2% (95% CI 83.9–97.1).

Does it work against new variants?

Yes, but vaccine effectiveness may be reduced against some variants and more data are needed.

Alpha (B.1.1.7; first detected in UK): Data from Novovax suggest a vaccine efficacy of 86.3% (95% CI 71.3–93.5) against symptomatic infection.

Beta (B.1.351, first detected in South Africa): Data from Novovax suggest a vaccine efficacy of 48.6% (95% CI 28.4–63.1) against symptomatic infection, 55.4% (95% CI 35.9–68.9) in HIV-negative participants.

Data from a phase IIb study published in The New England Journal of Medicine on 5 May 2021, suggest a vaccine efficacy among 2,684 participants of 49.4% (95% CI 6.1–72.8) at least 7 days after the second dose, with all cases classed as mild-to-moderate except one severe case in the placebo group. Among HIV-negative participants, vaccine efficacy was 60.1% (95% CI 19.9–80.1). The B.1.351 variant accounted for 92.7% of sequenced cases.

Gamma (P1, first detected in Japan/Brazil): No evidence yet.

Delta (B.1.617.2, first detected in India): No evidence yet.

Does it work in older people?

Yes, although more data are needed.

Just over a quarter (27%) of trial participants were aged >65 years; there was one case of COVID-19 in the vaccine group compared with nine in the placebo group.

The results of a phase III trial of almost 30,000 participants in Mexico and the US, announced by Novavax on 14 June 2021, indicated vaccine efficacy was 91.0% (95% CI 83.6–95.0) among “high-risk” populations (defined as over age 65, under age 65 with certain comorbidities or having life circumstances with frequent COVID-19 exposure), with 62 cases in the placebo group and 13 in the vaccine group.

Does it reduce transmission?

We don’t know yet.

Animal studies suggest transmission can be prevented entirely but this has not yet been confirmed in humans.

Are there any safety concerns?

Analyses of the UK and South Africa trials showed that the vaccine is well-tolerated, with low levels of severe, serious and medically attended adverse events at day 35, balanced between vaccine and placebo group. The same was found for the US/Mexico trial.

Full product information is not yet available.

GSK/Sanofi (CoV2 preS dTM)

Is it approved in the UK?

No.

How many doses have been ordered/pre-ordered?

60 million.

What are the storage requirements?

Store at 2–8ºC.

What are the latest data on effectiveness?

GSK and Sanofi announced on 17 May 2021 that their vaccine candidate has demonstrated strong immune responses across all adult age groups in a phase II trial involving 722 participants. Seroconversion after two doses was between 95% and 100%, with higher levels of neutralising antibodies observed in younger adults (18 to 59 years old). After a single injection, high neutralising antibody levels were generated in participants with evidence of prior SARS-CoV-2 infection.

The news comes after the partnership was forced to reformulate the vaccine following a weaker response in older people owing to an insufficient concentration of the antigen in the vaccine.

Does it work against new variants?

We don’t know yet.

Alpha (B.1.1.7; first detected in UK): No evidence yet.

Beta (B.1.351, first detected in South Africa): No evidence yet.

Gamma (P1, first detected in Japan/Brazil): No evidence yet.

Delta (B.1.617.2, first detected in India): No evidence yet.

Does it work in older adults?

Not in early trials.

Phase I/II trial results announced by GSK/Sanofi showed insufficient neutralising antibody titres in adults over the age of 50 years. The interim analysis was published in The Lancet on 19 April 2021.

Does it reduce transmission?

We don’t know yet.

Data not yet available.

Are there any safety concerns?

Data not yet available.

Full product information is not yet available.

Inactivated whole virus vaccines

Inactivated whole virus vaccines are made using an old technology, which delivers an inactivated version of the SARS-CoV-2 virus directly into the body, along with an adjuvant, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body (see Figure).

Valneva (VLA2001)

Is it approved in the UK?

No.

How many doses have been ordered/pre-ordered?

100 million.

What are the storage requirements?

Store at 2–8ºC.

What are the latest data on effectiveness?

Phase I/II trial results in 153 healthy adults aged 18 to 55 years old, announced by Valneva on 6 April 2021, suggest the vaccine is immunogenic, with more than 90% of all study participants developing significant levels of antibodies to the SARS-CoV-2 virus spike protein across three dose groups tested. In the high dose group, after two doses, antibody titres were at or above levels for a panel of convalescent sera. 

Does it work against new variants?

We don’t know yet.

Alpha (B.1.1.7; first detected in UK): No evidence yet.

Beta (B.1.351, first detected in South Africa): No evidence yet.

Gamma (P1, first detected in Japan/Brazil): No evidence yet.

Delta (B.1.617.2, first detected in India): No evidence yet.

Does it work in older adults?

We don’t know yet.

Data not yet available.

Does it reduce transmission?

We don’t know yet.

Data not yet available.

Are there any safety concerns?

Phase I/II trial results, announced by Valneva on 6 April 2021, suggest the vaccine is well tolerated with no safety concerns identified.

Full product information is not yet available.

Panel: Priority groups for vaccination 

Phase 1:

  1. Residents in a care home for older adults and their carers
  2. All those aged 80 years and over, and frontline health and social care workers
  3. All those aged 75 years and over
  4. All those aged 70 years and over, and clinically extremely vulnerable individuals
  5. All those aged 65 years and over
  6. All those aged 16–64 years with underlying health conditions that put them at higher risk of serious disease and mortality, and adult household contacts of adults with severe immunosuppression
  7. All those aged 60 years and over
  8. All those aged 55 years and over
  9. All those aged 50 years and over

Phase 2:

  1. All those aged 40–49 years
  2. All those aged 30–39 years
  3. All those aged 18–29 years

The Joint Committee on Vaccination and Immunisation strongly advises the following groups to take up a vaccine as soon as it is offered:

  • Men
  • People from black, Asian and minority ethnic communities
  • People with a body mass index over 30
  • People living in socio-economically deprived areas

Latest:

  • The Oxford/AstraZeneca entry was updated on 20 July 2021 to include previous episodes of capillary leak syndrome as a contraindication.
  • The Oxford/AstraZeneca, Pfizer/BioNTech, Moderna entries were updated on 20 July 2021 to include the latest data on cases of blood clots with low platelets, and cases of myocarditis and pericarditis.
  • The Janssen entry was updated on 20 July 2021 to include a small study on duration of antibody and T cell responses and efficacy against the Delta variant.
  • The Pfizer/BioNTech and Oxford/AstraZeneca entries were updated on 12 July 2021 to include new data on vaccine efficacy in risk groups.
  • The Oxford/AstraZeneca, Pfizer/BioNTech, Moderna entries were updated on 12 July 2021 to include the latest data on cases of blood clots with low platelets, and cases of myocarditis and pericarditis.
  • The Janssen entry was updated on 12 July 2021 to include the EMA’s advice on vaccine use in patients with a history of capillary leak syndrome.
  • The Janssen entry was updated on 2 July 2021 to include a small laboratory study on vaccine efficacy against the Delta variant.

Illustrations: Alisdair Macdonald

Editorial advisers for the illustrations: Stephen Griffin, associate professor and chair, Virus Division, Microbiology Society, University of Leeds; Charles Bangham, chair in immunology and co-director of the Institute of Infection at Imperial College London.