COVID-19 vaccine boosters in the Asia-Pacific region in the context of Omicron

As the Omicron variant of concern rapidly spreads across the globe, some countries are scaling up their booster programs to help protect against the impending wave of infections. Omicron has mutations that allow it to evade vaccine immunity at least partially. Here we present available data on effectiveness of boosters, including against Omicron, and how this relates to the Asia-Pacific region. Early data from the UK suggests Pfizer/BioNTech boosters may enhance effectiveness against infection with Omicron from around 35% from 15 weeks after the second dose to over 70% (data not peer-reviewed).1Andrews N, Stowe J, Kirsebom F, et al. Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern. medRxiv. 2021. https://doi.org/10.1101/2021.12.14.21267615.Google Scholar In Denmark, boosters increased effectiveness against infection with Omicron from <10% by the third month after two doses to 55%. However, two doses still reduces the risk of hospitalisation by 63% for AstraZeneca, and 74% for Pfizer/BioNTech or Moderna, even if protection against infection has been largely lost against Omicron.2Ferguson N. Ghani A. Hinsley W. Volz E. Hospitalisation Risk for Omicron Cases in England. Imperial College London, 2021https://www.imperial.ac.uk/media/imperial-college/medicine/mrc-gida/2021-12-22-COVID19-Report-50.pdfGoogle Scholar Much of the evidence related to boosters pre-Omicron is still relevant for booster policy decisions although timelines may be accelerated due to the new variant, and the primary focus must remain on vaccinating those at high risk of severe outcomes.3McIntyre P.B. Aggarwal R. Jani I. et al.COVID-19 vaccine strategies must focus on severe disease and global equity.Lancet. 2021; https://doi.org/10.1016/S0140-6736(21)02835-XSummary Full Text Full Text PDF Scopus (2) Google Scholar Delta is still the predominant variant of COVID-19 worldwide by the 6th January 2022.4UK Health Security AgencySARS-CoV-2 Variants of Concern and Variants Under Investigation in England Technical Briefing 33. UK Health Security Agency, 2021Google Scholar Two doses of Pfizer/BioNTech, Moderna and AstraZeneca vaccines are highly effective against Delta initially, although this wanes over time. In the UK, effectiveness of both AstraZeneca and Pfizer/BioNTech against infection with Delta decreased 20% beyond 20 weeks after vaccination; and decreased 15% and 8%, respectively, against death (data not peer-reviewed).5Andrews N, Tessier E, Stowe J, et al. Vaccine effectiveness and duration of protection of Comirnaty, Vaxzevria and Spikevax against mild and severe COVID-19 in the UK. medRxiv. 2021. https://doi.org/10.1101/2021.09.15.21263583Google Scholar However, evidence from Scotland and Brazil indicates effectiveness against severe outcomes and death wanes within three months of the second dose of AstraZeneca.6Katikireddi S.V. Cerqueira-Silva T. Vasileiou E. et al.Two-dose ChAdOx1 nCoV-19 vaccine protection against COVID-19 hospital admissions and deaths over time: a retrospective, population-based cohort study in Scotland and Brazil.Lancet. 2021; https://doi.org/10.1016/S0140-6736(21)02754-9Summary Full Text Full Text PDF Scopus (3) Google Scholar In Canada, effectiveness of the mRNA vaccines declined about 10% against infection by the eighth month, and by the fourth month for AstraZeneca, although effectiveness against hospitalisation was maintained (data not peer-reviewed).7Skowronski DM, Setayeshgar S, Febriani Y, et al. Two-dose SARS-CoV-2 vaccine effectiveness with mixed schedules and extended dosing intervals: test-negative design studies from British Columbia and Quebec, Canada. medRxiv. January 2021. https://doi.org/10.1101/2021.10.26.21265397Google Scholar A Pfizer/BioNTech booster showed 95% efficacy against disease, and 93% and 81% effectiveness in Israel against hospitalisation and death, respectively, compared with those who received two doses at least five months previously.8Barda N. Dagan N. Cohen C. et al.Effectiveness of a third dose of the BNT162b2 mRNA COVID-19 vaccine for preventing severe outcomes in Israel: an observational study.Lancet. 2021; https://doi.org/10.1016/S0140-6736(21)02249-2Summary Full Text Full Text PDF PubMed Scopus (38) Google Scholar By reducing infection, boosters can also indirectly help protect the clinically vulnerable and unvaccinated but with Omicron this seems to be quite short-lived.4UK Health Security AgencySARS-CoV-2 Variants of Concern and Variants Under Investigation in England Technical Briefing 33. UK Health Security Agency, 2021Google Scholar Increasing circulating antibody will inhibit initial viral invasion of cells in the airway, thereby reducing infection and transmission, even if those who have not received boosters are relatively protected against severe disease through delayed B and T cell memory responses. Breakthrough infections have been shown to have lower viral load than infections in unvaccinated individuals, making them less infectious, an effect that also wanes and is restored with boosters.9Levine-Tiefenbrun M. Yelin I. Alapi H. et al.Viral loads of Delta-variant SARS-CoV-2 breakthrough infections after vaccination and booster with BNT162b2.Nat Med. 2021; https://doi.org/10.1038/s41591-021-01575-4Crossref Scopus (10) Google Scholar However, these are additional benefits and the focus needs to remain on preventing severe illness in the vulnerable.3McIntyre P.B. Aggarwal R. Jani I. et al.COVID-19 vaccine strategies must focus on severe disease and global equity.Lancet. 2021; https://doi.org/10.1016/S0140-6736(21)02835-XSummary Full Text Full Text PDF Scopus (2) Google Scholar WHO recommends a third dose as part of the initial vaccination schedule for the immunocompromised; and a booster dose with either the same or a different vaccine following the inactivated vaccines, Sinovac and Sinopharm, due to lower initial efficacy and more rapid waning. Nearly three-quarters of 1.1 billion doses of Sinopharm and Sinovac distributed worldwide have been in the Asia-Pacific region, where much of the population received two doses and will not be fully protected, especially from Omicron. In Pacific Island Countries (PICs), boosters will be important regardless of the primary schedule, due to extremely high rates of obesity, diabetes and other conditions predisposing to severe COVID-19. In US-affiliated PICs and French territories, mostly mRNA vaccines and the viral vector vaccine, Johnson & Johnson, have been used. In southern PICs, AstraZeneca and Sinopharm have predominated. Booster administration depends very much on vaccine availability, with about 120,000 boosters administered to date, mainly in US-affiliated PICs. The optimal vaccine to boost with is still being determined. Mixing and matching boosters using all combinations of Pfizer/BioNTech, Moderna and Johnson & Johnson in the US showed homologous boosters increased antibody titres by 4.2 to 20-fold and heterologous boosters 6.2 to 76-fold (data not peer-reviewed).10Atmar RL, Lyke KE, Deming ME, et al. Heterologous SARS-CoV-2 booster vaccinations: preliminary report. medRxiv. January 2021. https://doi.org/10.1101/2021.10.10.21264827.Google Scholar UK data has shown that boosting with Pfizer/BioNTech, AstraZeneca, Moderna, Johnson & Johnson, Novavax or CureVac, following Pfizer/BioNTech or AstraZeneca primary series, boosts antibody and neutralising responses.11Munro A.P.S. Janani L. Cornelius V. et al.Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1 nCov-19 or BNT162b2 in the UK (COV-BOOST): a blinded, multicentre, randomised, controlled, phase 2 trial.Lancet. 2021; https://doi.org/10.1016/S0140-6736(21)02717-3Summary Full Text Full Text PDF Scopus (18) Google Scholar AstraZeneca or Pfizer/BioNTech boosters following Sinovac primary series yielded 4 to 8-fold higher neutralizing antibodies than Sinopharm boosters (data not peer-reviewed).12Angkasekwinai N, Niyomnaitham S, Sewatanon J, et al. The immunogenicity and safety of different COVID-19 booster vaccination following CoronaVac or ChAdOx1 nCoV-19 primary series. medRxiv. January 2021. https://doi.org/10.1101/2021.11.29.21266947.Google Scholar Due to surges in Delta infections and severe outcomes following rollout of inactivated vaccines, some countries are offering heterologous boosters: Indonesia is offering Moderna boosters; Thailand, AstraZeneca or Pfizer/BioNTech boosters; Laos and Cambodia, AstraZeneca boosters; Singapore, mRNA vaccine boosters; and the United Arab Emirates, Bahrain and Mongolia, Pfizer/BioNTech boosters. As countries roll out boosters, and increasingly so in the context of Omicron, this will impact global vaccine supply and create further inequity. To address this, the Coalition for Epidemic Preparedness Innovations is evaluating fractional dose boosters. Fractional doses could potentially reduce side effects as well as provide a dose-stretching and more affordable option, both factors particularly important in the Asia-Pacific region where vaccine supply has been a constraint on rollout. Immunogenicity studies show that half-dose Pfizer/BioNTech or Moderna boosters induce high neutralising antibodies against variants and even lower doses with intradermal administration are showing promising results. The focus needs to remain on preventing severe outcomes. There is clear evidence that a third dose is needed for the elderly and immunocompromised populations for any variant. Protection against severe outcomes from Omicron as well as Delta appears to be mostly preserved following a primary series of the Pfizer/BioNTech, Moderna and AstraZeneca vaccines. Nevertheless, alongside efforts to administer boosters, the priority should remain to vaccinate a high proportion of the world's eligible population with two doses of vaccine. Novel administration strategies to reduce the amount of vaccine needed should be explored to mitigate vaccine shortage. JDH wrote the original draft. All other authors contributed to reviewing and editing the manuscript. All authors declare no conflicts of interest. No funding was provided for this work.

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