HTB

Plans for universal third vaccine dose for UK adults from September

Simon Collins, HIV i-Base

On 30 June 2021, the Joint Committee for Vaccination and Immunisation (JCVI) in the UK issued a statement outlining plans for extending the COVID-19 vaccine programme to routinely increase to a third dose. [1]

The statement falls short of recommending third doses, using language to outline plans “should a booster programme be needed”. Priority will closely follow the stages used for initial access. This includes “care home residents, people aged over 70, frontline health and social care workers, clinically extremely vulnerable adults and those who are immunosuppressed”.

However, the Welsh government reports the JCVI statement as providing “a level of certainty” around stage 3 of the vaccine programme. Wales has been planning a booster dose in September/October for priority groups 1 to 9. [2]

Both statements refer to booster doses as likely to be using current vaccines, rather than new versions that have been reformulated to overcome new variants. Neither statement discusses the evidence supporting a third vaccine or links directly to the JCVI report.

Several research groups have reported that current vaccines are likely to provide lower protection against variants, especially now that Delta (B.1.617.2) is now dominant in the UK.

This includes >5-fold overall reductions in neutralising sensitivity to the Delta (B.1.617.2) variant. By comparison, >6-fold reductions against Beta (B.1.351) have already been associated with reduced vaccine efficacy. [3]

This study from the COVID-19 Genomics UK group, currently published ahead of peer review, reports phenotypic reductions in sensitivity of neutralising titres of 7.77, 11.30 and 9.56-fold respectively to pseudoviruses of the B.1.617.1, B.1.617.2 (Delta) and B.1.351 (Beta) variants, following two doses of the Pfizer mRNA vaccine.

Fold changes after vaccination with two doses of the Oxford/AZ vaccine were 0.69, 4.01 and 1.48 respectively, although this antibody responses to mRNA vaccines achieve significantly higher overall responses than the Oxford/AZ vaccine.

Public Health England have already reported vaccine efficacy against the Delta variant ‘modestly’ drops to 88% and 59% following two doses of the Pfizer vaccine and Oxford/AZ vaccines respectively. [4]

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Access to a third vaccine will hopefully improve antibody responses in people with low levels after two doses.

However, the proposal for a universal third vaccine seems linked to concerns over reduced efficacy against variants and potentially to waning responses after six months on a population rather than individual level.

The makes access to the data used for the JCVI decisions of public interest and these should be published.

Access to the data is also needed to understand the political and ethical issues of providing a third vaccine to all adults in the UK, given the broad inequity of access to vaccines in low-income countries globally. This concerns will be multiplied if  similar policy is adopted in other high-income countries.

A national UK trial of a third-dose booster is also already underway. [5]

Several HTB articles since May 2021 have reported low or absent antibody responses in significant percentages of people with reduced immune function. [6, 7 8, 9, 10]

This is very different from all adults in the UK requiring a third vaccine dose – unless the JCVI data shows otherwise.

A more selected approach to boosting doses would be possible in individual tests for vaccine responses become available.

Although several research groups are already working on point-of-care technology, including lateral flow tests to detect neutralising antibodies, none have so far been approved. [11, 12]

References

  1. UK government press release. JCVI issues interim advice on COVID-19 booster vaccination. (30 June 2021).
    https://www.gov.uk/government/news/jcvi-issues-interim-advice-on-covid-19-booster-vaccination
  2. Wales government report. COVID-19 Vaccination – JCVI announcement on Phase 3. (30 June 2021).
    https://gov.wales/written-statement-covid-19-vaccination-jcvi-announcement-phase-3
  3. David C et al. Reduced neutralisation of the Delta (B.1.617.2) SARS-CoV-2 variant of concern following vaccination. MedRxiv pre-peer review. doi: 10.1101/2021.06.23.21259327. (28 June 2021).
    https://www.medrxiv.org/content/10.1101/2021.06.23.21259327v1
  4. Bernal  JL et al. Effectiveness of COVID-19 vaccines against the B.1.617.2 variant. medRxiv, 2021. doi: 0.1101/2021.05.22.21257658. (2021). (24 May 2021).
    https://www.medrxiv.org/content/10.1101/2021.05.22.21257658v1
  5. COV-Boost vaccine trial
    https://www.covboost.org.uk/home
  6. Failure of mRNA vaccines to produce antibody responses in late diagnosed HIV with low CD4 count and high viral load. HTB, (1 July 2021).
    https://i-base.info/htb/40779
  7. Third vaccine dose increases immune response to 68% in French transplant recipients. HTB, (1 July 2021).
    https://i-base.info/htb/40812
  8. Third COVID-19 vaccine dose in US cohort of people on immune-suppressing treatment: safety and ethical issues. HTB, (1 July 2021).
    https://i-base.info/htb/40843
  9. France routinely recommends third dose of COVID-19 vaccine for some people with reduced immune function. HTB, (1 June 2021).
    https://i-base.info/htb/40634
  10. Cases of COVID-19 reported including deaths in care home residents after full-course vaccination. HTB, (1 June 2021).
    https://i-base.info/htb/40686
  11. Fulford TS et al. A point-of-care lateral flow assay for neutralising antibodies against SARS-CoV-2. Version 2 (updated to include human data). MedRxiv pre-peer review. doi: 10.1101/2021.04.12.21255368. (10 May 2021).
    https://www.medrxiv.org/content/10.1101/2021.04.12.21255368v2.article-info
  12. Wang JJ et al. Rapid lateral flow tests for the detection of SARS-CoV-2 neutralizing antibodies. Expert Rev Mol Diagn. 2021: 1–8. doi: 10.1080/14737159.2021.1913123. (12 April 2021).
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054491

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