COVID-19 Vaccine Boosters in The Asia-Pacific Region in The Context Of Omicron

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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 the effectiveness of boosters, including against Omicron, and how this relates to the Asia-Pacific region. Early data from the UK suggests Pfifizer/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effectiveness against infection with Omicron from around 35% from 15 weeks after the second dose to over 70% (data not peer-reviewed).1 In Denmark, boosters increased effectiveness against infection with Omicron from <10% by the third month after two doses to 55%. However, two doses still reduce the risk of hospitalization by 63% for AstraZeneca, and 74% for Pfizer/BioNTech or Moderna, even if protection against infection has been largely lost against Omicron.2

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.3 Delta is still the predominant variant of COVID-19 worldwide by the 6th January 2022.4 Two doses of Pfizer/BioNTech, Moderna, and AstraZeneca vaccines are highly effective against Delta initially, although this wanes over time. In the UK, the effectiveness of both Astra-Zeneca 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with Delta decreased 20% beyond 20 weeks after vaccination; and decreased 15% and 8%, respectively, against death (data not peer-reviewed).5 However, evidence from Scotland and Brazil indicates effectiveness against severe outcomes and death wanes within three months of the second dose of AstraZeneca.6 In Canada, the effectiveness of the mRNA vaccines declined about 10% against infection by the eighth month, and by the fourth month for AstraZeneca, although effectiveness against hospitalization was maintained (data not peer-reviewed).7

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A Pfizer/BioNTech booster showed 95% efficacy against disease, and 93% and 81% effectiveness in Israel against hospitalization and death, respectively, compared with those who received two doses at least five months previously.8 By reducing infection, boosters can also indirectly help protect the clinically vulnerable and unvaccinated but with Omicron this seems to be quite short-lived.4 Increasing circulating antibodies 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 a lower viral load than infections in unvaccinated individuals, making them less infectious, an effect that also wanes and is restored with boosters.9

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However, these are additional benefits and the focus needs to remain on preventing severe illness in the vulnerable.3 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 titers by 4.2 to 20-fold and heterologous boosters 6.2 to 76-fold (data not peer-reviewed).10 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 neutralizing responses.11 AstraZeneca or Pfizer/BioNTech boosters following Sinovac primary series yielded 4 to 8-fold higher neutralizing antibodies than Sinopharm boosters (data not peer-reviewed).12 Due to surges in Delta infections and severe outcomes following the 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 the global vaccine supply and create further inequity.

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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 Pfifizer/BioNTech or Moderna boosters induce high neutralizing 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 number of vaccines needed should be explored to mitigate vaccine shortage.

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References

1 Andrews N, Stowe J, Kirsebom F, et al. Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern. medRxiv. 2021.

2 Ferguson N, Ghani A, Hinsley W, Volz E. Hospitalisation Risk for Omicron Cases in England. Imperial College London; 2021.

3 McIntyre PB, Aggarwal R, Jani I, et al. COVID-19 vaccine strategies must focus on severe disease and global equity. Lancet. 2021.

4 UK Health Security Agency. SARS-CoV-2 Variants of Concern and Variants Under Investigation in England Technical Briefing 33. UK Health Security Agency; 2021. 23 December.

5 Andrews 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/10.1101/2021.09.15.21263583.

6 Katikireddi SV, 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.

7 Skowronski 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.

8 Barda 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.

9 Levine-Tiefenbrun M, Yelin I, Alapi H, et al. Viral loads of Deltavariant SARS-CoV-2 breakthrough infections after vaccination and booster with BNT162b2. Nat Med. 2021.

10 Atmar RL, Lyke KE, Deming ME, et al. Heterologous SARS-CoV-2 booster vaccinations: a preliminary report. medRxiv. January 2021.

11 Munro APS, 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 (COVBOOST): a blinded, multicentre, randomized, controlled, phase 2 trial. Lancet. 2021.

12 Angkasekwinai 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.