Monovalent vs Bivalent Vaccines for COVID-19

The Australian Technical Advisory Group on Immunisation (ATAGI) has advised the Australian Government regarding the use of new monovalent Omicron XBB.1.5 vaccines for eligible recipients. The new monovalent vaccines will be available from 11 December 2023, coinciding with the expected rise in COVID-19 cases over the holiday period.


With a relatively large number of people with COVID-19 in the community already and many people now eligible for a booster, people could wonder whether to receive a booster dose of a currently available bivalent vaccine or to wait for one of the new monovalent vaccines.

Monovalent vs Bivalent

The mRNA COVID-19 vaccines developed by Pfizer and Moderna contain genetic information (mRNA) derived from the SARS-CoV-2 virus. This genetic information is used by the body to produce individual proteins (called antigens) that imitate a small portion of those found on the full wild-type SARS-CoV-2 virus.1 The body then uses these self-produced proteins to train an immune response in preparation for possible infection. Because the body has prepared an immune response ahead of time, it is better able to respond to a COVID-19 infection, reducing the severity of the disease and the likelihood of hospitalisation and death.2 As the wild-type SARS-CoV-2 virus continues to mutate, however, the vaccines used to protect against infection must also be adapted.3,4 To do this, portions of genetic information derived from more recently circulating SARS-CoV-2 variants can be included in a vaccine to offer up to date protection.4

‘Bivalent’, in this instance, refers to a vaccine that contains genetic information from two strains of the same virus. Currently available bivalent COVID-19 vaccines contain genetic information from both the original wild-type or ‘Alpha’ strain and an earlier Omicron strain.5 The soon-to-be-available monovalent vaccine includes genetic information from the recent XBB.1.5 (‘Kraken’) variant and is designed to provide improved protection.6

While earlier vaccinations have been bivalent to protect against multiple circulating variants in the community, it has recently been proposed that monovalent vaccine boosters might provide improved protection since earlier variants of the virus are now rarely encountered, having been out-competed by new variants of the Omicron strain.4 As approximately 85% of Australians have received at least one dose of the COVID-19 vaccine,8 it is expected that ‘herd immunity’ should also limit the spread of ancestral strains should they resurface.9

While the monovalent vaccination targets XBB.1.5 (Kraken) due to its genetic similarities to other dominant variants, such as XBB.1.16 (Arcturus), EG.5 (Eris), and BA.2.86 (Pirola) it is expected that a monovalent Omicron XBB.1.5 vaccination would offer protection against earlier variants as well.6,10

Which vaccine should I get?

The short answer is that people should consult with their healthcare provider regarding the relative benefits of receiving a newer monovalent vaccine somewhat later or electing to receive a booster dose of a currently available bivalent booster. Both vaccines are safe and offer protection, reducing the risk of severe illness.

The ATAGI recommends the monovalent Omicron XBB.1.5 vaccines over other vaccines for use in children aged 5 years or older and adults who are currently recommended primary or additional doses of the COVID-19 vaccine. They do note, however, that existing bivalent vaccinations still offer strong protection against severe disease.11 While it is of limited benefit to enhance immunity against the original COVID-19 strain, an abundance of research demonstrates that bivalent mRNA vaccines still provide antibody immunity against the Omicron lineages.12-15 No safety concerns have been identified in the use of bivalent vaccinations.15-17

The monovalent Omicron XBB.1.5 vaccines have demonstrated significantly greater levels of neutralising antibodies against currently circulating Omicron subvariants in people who have received at least a primary course of vaccination.6 Preclinical trials have similarly found that the Omicron monovalent vaccines induced higher antibody binding titers and neutralisation activities compared to the bivalent vaccine.18 This data suggests that the monovalent vaccine provides modestly enhanced protection from severe disease compared to older vaccines.19 The use of monovalent Omicron vaccines are thought to be associated with no higher inherent risks compared to the bivalent vaccines.6

Conclusion

There has been a recent increase in the number of active COVID-19 infections in Australia and it is recommended that all people who have not yet received a recommended 2023 booster dose receive theirs as soon as possible. All currently available vaccines are expected to provide benefit to eligible people, however the monovalent vaccine, available from the 11th of December is currently the preferred vaccine for children aged 5 years or older, and adults who are currently recommended a primary or additional dose of a COVID-19 vaccine. For those who have already received the recommended number of 2023 booster dose/s then no further dose or re-vaccination with the XBB.1.5 containing monovalent vaccine is recommended at this time.11 Ensuring vaccinations are up to date is of particular importance in preparation for the holiday period when many will be in contact with friends, family, and members of the broader community who may be vulnerable or immunocompromised.

References

  1. Rab S, Afjal, Javaid M, Haleem A, Vaishya R. An update on the global vaccine development for coronavirus. Diabetes Metab Syndr. 2020;14(6):2053-5.
  2. Peters M, Marnie C. ANMF COVID-19 resources: How do the COVID-19 vaccines work? [Internet]. Australian Nursing and Midwifery Federation; 2021 Feb. Available from: https://www.anmf.org.au/media/0ymjufj3/anmf_covid-19_resource-how_the_covid-19_vaccines_work.pdf.
  3. Farhud DD, Mojahed N. SARS-COV-2 notable mutations and variants: A review article. Iran J Public Health. 2022;51(7):1494-501.
  4. Clarke J, Peters M. Evidence Brief: The World Health Organization’s Statement on the antigen composition of COVID-19 vaccines [Internet]. Aust Nurs Midwifery J. 2023. Available from: https://anmj.org.au/evidence-brief-the-world-health-organizations-statement-on-the-antigen-composition-of-covid-19-vaccines/
  5. Shrestha NK, Burke PC, Nowacki AS, Simon JF, Hagen A, Gordon SM. Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine. Open Forum Infect Dis. 2023;10(6).
  6. Chalkias S, McGhee N, Whatley JL, Essink B, Brosz A, Tomassini JE, et al. Safety and immunogenicity of XBB.1.5-containing mRNA Vaccines. medRxiv. 2023.
  7. Kayser V, Ramzan I. Vaccines and vaccination: history and emerging issues. Hum Vaccin Immunother. 2021;17(12):5255-68.
  8. Department of Health and Aged Care. COVID-19 vaccine rollout update – 10 November 2023 [Internet]. 2023 Nov 11 [cited 2023 November 28]. Available from: https://www.health.gov.au/resources/publications/covid-19-vaccine-rollout-update-10-november-2023?language=en
  9. Suryawanshi YN, Biswas DA. Herd immunity to fight against COVID-19: A narrative review. Cureus. 2023;15(1):e33575.
  10. Patel N, Trost JF, Guebre-Xabier M, Zhou H, Norton J, Jiang D, et al. XBB.1.5 spike protein COVID-19 vaccine induces broadly neutralizing and cellular immune responses against EG.5.1 and emerging XBB variants. Sci Rep. 2023;13(1):19176.
  11. Department of Health and Aged Care. ATAGI recommendations on use of the Moderna and Pfizer monovalent Omicron XBB.1.5 COVID-19 vaccines 2023 [Internet]. 2023 Nov 20 [cited 2023 Nov 27]. Available from: https://www.health.gov.au/news/atagi-recommendations-on-use-of-the-moderna-and-pfizer-monovalent-omicron-xbb15-covid-19-vaccines#:~:text=All%20currently%20available%20COVID%2D19,of%20COVID%2D19%20vaccine%20according.
  12. Fang Z, Monteiro VS, Hahn AM, Grubaugh ND, Lucas C, Chen S. Bivalent mRNA vaccine booster induces robust antibody immunity against Omicron lineages BA.2, BA.2.12.1, BA.2.75 and BA.5. Cell Discov. 2022;8(1):108.
  13. Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, et al. Three-month antibody persistence of a bivalent Omicron-containing booster vaccine against COVID-19. Nat Commun. 2023;14(1):5125.
  14. Scheaffer SM, Lee D, Whitener B, Ying B, Wu K, Liang C-Y, et al. Bivalent SARS-CoV-2 mRNA vaccines increase breadth of neutralization and protect against the BA.5 Omicron variant in mice. Nat Med. 2023;29(1):247-57.
  15. Chalkias S, Harper C, Vrbicky K, Walsh SR, Essink B, Brosz A, et al. A bivalent Omicron-containing booster vaccine against Covid-19. N Engl J Med. 2022;387(14):1279-91.
  16. Andersson NW, Thiesson EM, Hansen JV, Hviid A. Safety of BA.4-5 or BA.1 bivalent mRNA booster vaccines: nationwide cohort study. BMJ. 2023;382:e075015.
  17. Hause AM, Marquez P, Zhang B, Myers TR, Gee J, Su JR, et al. Safety monitoring of bivalent COVID-19 mRNA vaccine booster doses among persons aged ≥12 Years – United States, August 31-October 23, 2022. MMWR Morb Mortal Wkly Rep. 2022;71(44):1401-6.
  18. Li W, Zhao T, Tao B, Zhao L, Xiao H, Ding X, et al. Monovalent Omicron COVID-19 vaccine triggers superior neutralizing antibody responses against Omicron subvariants than Delta and Omicron bivalent vaccine. Hum Vaccin Immunother. 2023;19(2):2264589.
  19. World Health Organization. COVID-19 vaccines 2023 [Internet]. 2023 [cited 2023 Nov 11]. Available from: https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines.

*ALERT* Evidence regarding COVID-19 is continually evolving. This resource will be updated regularly to reflect new emerging evidence but may not always include the very latest evidence in real-time.

Authors:

Jarrod Clarke, Casey Marnie, and Micah DJ Peters are at the National Policy Research Unit (Federal Office), Australian Nursing and Midwifery Federation (ANMF) and University of South Australia, Clinical and Health Sciences, Rosemary Bryant AO Research Centre. Dr Peters also holds adjunct appointments at the University of Adelaide with Health Evidence Synthesis, Recommendations and Impact (HESRI) in the School of Public Health and the School of Nursing, Health and Medical Sciences.

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