Bivalent omicron (BA.1) booster vaccination against SARS-CoV-2

Abstract

A highly virulent novel coronavirus known as SARS-CoV-2 emerged in 2019, posing a challenge to all humankind. 1 The unprecedentedly rapid development and deployment of effective vaccines substantially reduced the burden of COVID-19, and rapid and comprehensive vaccination programmes protected the majority of the population in high-income countries. Unfortunately, neither vaccination with first-generation vaccines based on the original Wuhan strain nor natural infection provides sterilising immunity against SARS-CoV-2. Despite the presence of proofreading-repair activity, the spontaneous mutation rate of SARS-CoV-2 amounts to around 1·3 × 10–6 per base per infection cycle. 2 As a result, many mutants have emerged and spread around the world since 2019. The most important representatives include alpha (B.1.1.7), beta (B.1.351), delta (B.1.617.2), gamma (P1), 3 and omicron (B.1.1.159) variants, along with omicron subvariants BA.1, BA.2, BA.4, and BA.5. 4 Omicron causes predominantly mild disease and is less likely to result in severe disease compared with the delta variant, but its high contagiousness raises serious concern. The protection rate against the omicron BA.1 variant after a previous SARS-CoV-2 infection is estimated at only 36·1%, although protection against the severe disease remains as high as 90·2%. 5 Several studies have found first-generation vaccines to be less effective against omicron than previous SARS-CoV-2 variants.6, 7 Omicron variants can effectively evade neutralising antibodies induced by both natural infection and vaccination in individuals who have received two or three doses of a vaccine. Therefore, the vaccination strategy should consider the emergence of new variants, which mitigates the development of new bivalent vaccines. BNT162b2 and mRNA-1273.214 are two bivalent mRNA vaccines that encode Wuhan-hu-1 and BA.1 spike (S) proteins. These vaccines were shown to elicit more effective neutralising antibodies response against both the original ancestral strain and the omicron variant.8, 9 First clinical trials of the vaccines showed that neutralising antibody response against the omicron variant was superior to that induced by the corresponding first-generation monovalent vaccine that encodes only the ancestRal Wuhan-Hu-1 S protein. In their Lancet Infectious Diseases publication, Hugo van der Kuy and colleagues 10 have reported on the immunogenicity and reactogenicity of these vaccines in individuals primed with adenovirus or first-generation mRNA-based vaccines that encode the Wuhan-Hu-1 spike protein. As a part of the open-label, multicentre, randomised controlled SWITCH ON trial, health-care workers aged 18–65 years were divided into four groups: (1) Ad26.COV2.S prime and BNT162b2 OMI BA.1 boost (Ad/P), (2) mRNA-based prime and BNT162b2 OMI BA.1 boost (mRNA/P), (3) Ad26.COV2.S prime and mRNA-1273.214 boost (Ad/M), and (4) mRNA-based prime and mRNA-1273.214 boost (mRNA/M). The booster vaccinations with either mRNA vaccine triggered a rapid recall of the humoral and cellular immune response within 7 days, regardless of the priming vaccine. The induced antibodies and T cells reacted with both the omicron BA.1 subvariant and the more antigenically distinct BA.5 omicron subvariant. However, these neutralising antibody concentrations were generally lower than those against ancestral SARS-CoV-2. 10 Hugo van der Kuy and colleagues' findings should be translated to other age groups (those younger than 18 years and those older than 65 years) and ethnic backgrounds cautiously due to the objective limitations of the trial. The role of previous infections might also have been underestimated and requires further investigation. A follow-up evaluation of the frequency of SARS-CoV-2 infection among study participants would help shed light on the effectiveness of the performed booster immunisation. Various vaccine platforms are used for priming and are likely to be used as boosters worldwide. Therefore, the effect of a different priming history needs to be considered, and the optimal prime-boost composition should be studied to choose the most efficient one in the future. Although the data presented by van der Kuy and colleagues showed no difference in the effectiveness of mRNA boosters following different priming regimes, 10 this might not be the case for other vaccines administered worldwide. Considering that the omicron variant mostly causes mild disease and is not expected to be the last SARS-CoV-2 variant, the question of whether further booster immunisation should be done or not remains unresolved. Although the paper by van der Kuy and colleagues provides some insights into mRNA vaccine boosters, we believe more studies are needed. © 2023 Flickr – Jernej Furman 2023 We declare no competing interests.