Could Beta variant containing COVID-19 booster vaccines tackle Omicron variants?

SARS-CoV-2 vaccines have been given to billions of people to protect against COVID-19, which was estimated to have saved more than 20 million lives. With the emergence of SARS-CoV-2 omicron variants and its subvariants, the effectiveness of prototype COVID-19 vaccines has dropped dramatically, although the protection against the severe disease from COVID-19 is still largely retained.^1,2 In an effort to broaden and further enhance protection against circulating and emerging SARS-CoV-2 variants, a number of variant-containing vaccines have been authorized for the use as booster vaccines, including bivalent ancestral/Omicron (BA.1 or BA.5) mRNA vaccines by Pfizer-BioNTech and Moderna, and the monovalent Sanofi-GSK Vidprevtyn Beta (a Beta variant containing protein-based vaccine).³

In The Lancet Regional Health – Europe, Júlia Corominas and colleagues report the findings of a randomized trial on the safety and immunogenicity of a bivalent protein-based vaccine (PHH-1V) compared to BNT162b2 among individuals who had received two doses of BNT162b2.⁴ PHH-1V consists of a recombinant RBD fusion heterodimer of the Beta variant (B.1.351) and the Alpha variant (B.1.1.7) of SARS-CoV-2, and adjuvanted with an oil-in-water emulsion based on squalene (SQBA). A total of 782 individuals (63.3% women, 98.7% white and ranging in age from 18 years to 76 years), without history of SARS-CoV-2 infection, were randomly assigned (2:1) to receive a third dose of either PHH-1V (n = 522) or BNT162b2 (n = 260) from 6 months to 12 months previously. The frequency of adverse reactions after a boost dose of PHH-1V was lower than that of BNT162b2 (89.3% vs 94.4%, p = 0.0219). The most frequent adverse reactions were fatigue, headache, myalgia and injection site pain, with most being mild to moderate in severity. No serious adverse events related to the vaccine occurred in either group.

Their study showed that a boosting dose of either PHH-1V or BNT162b2 resulted in substantial neutralizing antibody responses against SARS-CoV-2 ancestral strain and variants (Beta, Delta and Omicron BA.1). The neutralizing antibody response against ancestral SARS-CoV-2 was lower with PHH-1V than with BNT162b2 14 days and 28 days after boost, but a non-inferiority demonstrated at day 98. However, PHH-1V elicited a superior neutralizing antibody response against the Omicron subvariant BA.1 as compared with BNT162b2, with a geometric mean titre (GMT) ratio of 1.69 (95%CI [1.41, 2.00]), 1.52 [1.28, 1.82], 1.75 [1.22, 2.56] 14 days, 28 days and 98 days after booster dose, respectively.⁴ The monovalent Beta protein-based vaccine with AS03 adjuvant (Vidprevtyn Beta), as a heterologous booster, also induced consistently higher neutralizing antibody response against Omicron BA.1 than BNT162b2, with a GMT ratio of 2.53 (95% CI [1.80, 3.57]) at day 28.⁵ Beta variant containing booster vaccines could induce high cross-reactive immune responses against Omicron BA.1, which probably resulted from K417N, E484K and N501Y substitutions in Beta variant spike.

With the continuous and substantial evolution of SARS-CoV-2, a booster strain selection strategy should be based on the capability of eliciting broad cross-reactivity, especially against new emerging variants. Currently, Omicron BA.5/BA.2 sublineages BQ.1, BQ.1.1 and XBB have become the dominant strains, which demonstrated dramatically increased ability to evade neutralising antibodies, even those from people who received the bivalent ancestral/Omicron BA.5 mRNA booster or who are immunised and had previous breakthrough Omicron infection.⁶ Of note, the present study did not assess the neutralising antibody responses against BQ.1, BQ.1.1 and XBB. Whether PHH-1V booster could elicit high cross-neutralizing antibodies against circulating and emerging Omicron subvariants is needed to be warranted.

A preponderance of vaccine effectiveness data of variant-containing booster vaccines is derived from mRNA-based vaccines. Bivalent Omicron BA.1 containing booster vaccines elicited superior neutralising antibody responses against Omicron BA.1 compared to the corresponding prototype vaccines, with GMT ratio of 1.56–1.78.^7,8 Real-world data showed that bivalent Omicron BA.5-containing mRNA vaccines as a booster provided additional protection against symptomatic SARS-CoV-2 infection at a time of circulating Omicron sublineages BQ.1, BQ.1.1 and XBB predominated, with relative vaccine effectiveness of 30%–50%.^9,10 The relative performance of a Beta-booster vaccine compared to Omicron-containing booster vaccines will provide valuable data to inform vaccination policy decisions on variant-containing vaccines. As far as we know, a direct comparison of Beta-containing and Omicron-containing booster vaccines has not been done or published. However, comparison of results across trials should be considered with caution due to differences in population, the timing of booster and antibody assays. In addition, the generation of relative vaccine effectiveness data using variant-containing vaccines compared to ancestral virus-containing vaccines as soon as possible after they have been introduced into populations.

There are significant uncertainties related to the evolution of the virus, the characteristics of future variants, and the trajectory of the epidemic given increasing vaccine- and infection-induced immunity globally. The current approach to update vaccine antigen composition may not be sustainable in the long term. In order to address the challenges of the continuous evolution of SARS-CoV-2 and the risk of other emerging coronaviruses with pandemic potential, pan-SARS-CoV2 or pan-sarbecovirus vaccines are urgently needed but will be technically challenging.

Contributors

P.J. contributed to literature search and drafting the manuscript. F.Z. and P.J. contributed to critical review and revising of the manuscript.

Declaration of interests

The author declares no competing interests.