After three years of living with masks and travel restrictions, most COVID-related restriction policies were lifted in March, 2023. While the mood of citizens in Hong Kong is boosted, there are rising number of COVID and influenza cases. Scientists round the globe have been surveilling the evolution of SARS-CoV-2 and there are reports of constant mutation of the virus, together with report of declining antibody level in the blood, one question, thus, was raised: Should we get annual SARS-CoV-2 vaccine booster?

Vaccination is a procedure which mimic natural infection with substances constructed from pathogens, which can be the original pathogen in less harmful state (inactivated), part of the pathogen (protein subunits), or novel platforms such as the mRNA vaccines. After natural infection or vaccination, our immune system develops memory cells which are specific to the pathogen and respond quickly when we encounter the same pathogen. A faster immune response can suppress the replication of pathogens and reduce the damage done to our body. Moreover, if the number of pathogens is suppressed, there is lower risk of transmission to others. Therefore, vaccination can reduce rate of infection and severity of illness caused by infectious disease.

To design a vaccine against a specific pathogen, a target is needed, and this target is known as antigen. Antibody specific to the antigen can then bind and inhibit the pathogen possessing this specific antigen. Ideally, vaccination can induce immune response that is specific to this antigen without reacting to other molecules. Unfortunately, viruses do mutate and change their antigen, as a result, the immune response induced by a vaccine designed for the original virus may not be as effective against the mutated version. Vaccination, however, may still be partly protective against mutated virus for two reasons. Firstly, even though the antigen has mutated, there may be cross-reactivity of the antibodies, meaning that antibody may still bind to the pathogen; secondly, for each pathogen there is conserved antigens, which are antigens that barely mutate, for vaccines that uses inactivated pathogens, antibodies against these conserved regions are produced and could be protective.

For the influenza viruses, two major groups of antigens were considered for vaccine development, the Hemagglutinin (HA) and Neuraminidase (NA). Through the WHO Global Influenza Surveillance and Response System (GISRS), vaccine experts monitor and predict the strains of prevalent influenza viruses in the next flu seasons, and seasonal flu vaccines are then produced. Despite the endeavor, there could still be mismatch between the predicted circulating strain and the actual circulating strain. According to data from the United States, a mismatch may reduce the vaccine effectiveness from 49-60% to only 19% [1]. The challenge with SARS-CoV-2 is that it is difficult to predict how the virus mutates and to manufacture corresponding vaccine in advance. For example, in 2022, Bivalent vaccines (targeted both Wild Type and Omicron sub-lineage BA.5) were developed in view of emergence of Omicron variant. These bivalent vaccines were proven to be effective against BA.5, but less effective against more recently emerged strains like BQ.1.1 and XBB.1 [2]. Scientists have developed computer models to envision which virus variant are more likely to emerge [3], however, there is always a delay from detection of virus, manufacture of vaccines to the delivery of vaccines. What components should be included in the vaccine is the question we need to address before annual vaccination.

For annual vaccination, another consideration is whether everyone or selected groups of population should be vaccinated. Using our local data of influenza vaccine, inoculation appears to be cost-effective for the young and old, but not people aged 15 to 64[4]. Regarding SARS-CoV-2 vaccine, current evidence on fourth dose of vaccine booster suggested that repeated booster is more likely to benefit selected susceptible populations, such as the elderlies and the immunocompromised individuals [5]. It is also worth mentioning that vaccination is a medical procedure that comes with risks, including adverse events like myocarditis and thromboembolism after vaccination.

In conclusion, an analogy of annual vaccination would be like computer firewall updates, except this update comes with a low risk of corrupting your computer (i.e., vaccine adverse events). It is important to note that we are at the beginning of post-COVID era and more investigation is required to understand the pros and cons of SARS-CoV-2 annual vaccination. Based on data of flu vaccination and current SARS-CoV-2 vaccine studies, annual vaccination for selected population, instead of universal vaccination, should be more cost-effective and appropriate.

References:

1. Agor JK, Özaltın OY. Models for predicting the evolution of influenza to inform vaccine strain selection. Hum Vaccin Immunother. 2018;14(3):678-683. doi:10.1080/21645515.2017.1423152
2. Kurhade, C., Zou, J., Xia, H., Liu, M., Chang, H. C., Ren, P., Xie, X., & Shi, P. Y. (2023). Low neutralization of SARS-CoV-2 Omicron BA.2.75.2, BQ.1.1 and XBB.1 by parental mRNA vaccine or a BA.5 bivalent booster. Nature medicine, 29(2), 344–347. https://doi.org/10.1038/s41591-022-02162-x
3. Obermeyer, F., Jankowiak, M., Barkas, N., Schaffner, S. F., Pyle, J. D., Yurkovetskiy, L., Bosso, M., Park, D. J., Babadi, M., MacInnis, B. L., Luban, J., Sabeti, P. C., & Lemieux, J. E. (2022). Analysis of 6.4 million SARS-CoV-2 genomes identifies mutations associated with fitness. Science (New York, N.Y.), 376(6599), 1327–1332. https://doi.org/10.1126/science.abm1208
4. You, J. H., Ming, W. K., & Chan, P. K. (2015). Cost-effectiveness of quadrivalent influenza vaccine in Hong Kong - A decision analysis. Human vaccines & immunotherapeutics, 11(3), 564–571. https://doi.org/10.1080/21645515.2015.1011016
5. Khong, K. W., Zhang, R., & Hung, I. F. (2022). The Four Ws of the Fourth Dose COVID-19 Vaccines: Why, Who, When and What. Vaccines, 10(11), 1924. https://doi.org/10.3390/vaccines10111924

Author:
Mr Khong Ka Wa
MBBS 6, the University of Hong Kong

June 2023