In a recent study posted to the medRxiv* preprint server, researchers assessed the immunogenicity of a variant-adapted severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) recombinant protein vaccine boosted with an AS03 adjuvant.
There has been an unprecedented distribution of vaccines for coronavirus disease 2019 (COVID-19) in response to the pandemic. The ongoing emergence of additional SARS-CoV-2 variants of concern (VoCs) and decreasing resistance and protection against symptomatic infections highlight the necessity for novel and improved booster vaccinations to increase and widen protection. Although vaccines containing the SARS-CoV-2 Omicron variant were meant to comprise the main circulating strain, another strategy is to incorporate strains that offer comprehensive cross-protection against emerging variants.
About the study
In the present study, researchers investigated SARS-CoV-2 booster vaccines that contain Beta 5 (B.1.351) and/or prototype (D614) recombinant spike proteins with AS03 adjuvant (CoV2 preS dTM-AS03).
In a significant change to the Phase 2 primary vaccine series trial (NCT04762680) on 10 June 2021, cohorts 1 and 2 were included for phase 3 assessment of the immunogenicity and safety of monovalent B.1.351, monovalent D614, and bivalent D614+B.1.351 CoV-2 preS dTM-AS03 booster preparations. Booster categories in the two cohorts consisted of individuals from France, the United States, the United Kingdom, Spain, and Australia who had received a primary schedule of D614 messenger ribonucleic acid (mRNA) vaccines, including two doses of mRNA-1273 or BNT162b2) or adenovirus-vectored vaccine including one dose of Ad26.CoV2.S or two doses of ChAdOx1 nCoV-19 between four and ten months before enrolment.
Cohort 2 contained a subset of people from the United States and Honduras who had been primed with two doses of CoV2 preS dTM-AS03 carrying D614 antigen in the initial phase 2 study. Cohort 1 comprised a parallel and non-randomized control cohort of unvaccinated persons aged between 18 and 55 from the United States and Australia who were negative for SARS-CoV-2 antibodies using a rapid diagnostic test. Eligible individuals for the study included those with underlying medical issues, immunocompromised individuals, and those at increased risk of severe SARS-CoV-2 infection.
Participants in the booster cohort were categorized per priming vaccination and age group. The subjects from the cohort 1 booster sets were administered the monovalent D614 vaccine. In cohort 2, individuals previously vaccinated with an adenovirus-vectored or mRNA vaccine were randomly assigned to receive monovalent B.1.351 or bivalent D614+B.1.351 booster vaccines. In contrast, those initially vaccinated with CoV2 preS dTM-AS03 were randomly assigned to receive monovalent B.1.351 or monovalent D614 boosters. In the control cohort, participants were administered two injections of CoV2 preS dTM-AS03 possessing D614 antigen 21 days apart.
A lentivirus-based pseudovirus neutralization (PsVN) encoded the full-length spike protein of the D614G, Beta, or Omicron variants before neutralizing antibody responses to SARS-CoV-2 were quantified. The primary outcomes of the study involve individual serum PsVN titers against D614G at D1 and D15 for monovalent D614 vaccinees, against Beta for monovalent B.1.351 vaccinees, against B.1.351 and D614G for bivalent D614+B.1.351 vaccinees, and D614G almost 14 days following the final dose (D36) for the control cohort.
Among 806 participants, 803 participated in the monovalent D614 group, and 705 out of 707 participants registered in the monovalent B.1.351 group. In comparison, 621 out of 625 participants were a part of the bivalent D614+B.1.351 group that received booster doses. In the control cohort, a minimum of one primary dose of monovalent D614 was administered to 473 out of 479 SARS-CoV-2-nave subjects. In the three booster cohorts, the average age was between 43.7 and 50.4 years, with 22.2% to 37.5% of participants aged 56. The average age of participants in the control group was 37.50 years.
The D614G PsVN geometric mean titer (GMT) for subjects primed with BNT162b2 aged between 18 and 55 years rose from 339 on day 1 to 7,894 on day 15 after a monovalent D614 booster, suggesting a greater PsVN response after-booster in comparison to pre-booster. PsVN titers against D614G at day 15 were double those elicited following primary vaccination using CoV2 preS dTM-AS03 (D614) among the control group, suggesting non-inferiority to the control cohort. Thus, the co-primary goals for the D614 booster cohort were achieved.
The mRNA-primed, the adenovirus-vectored-primed, and the CoV2 preS dTM192 AS03 (D614) groups all exhibited a response that was superior to the pre-booster response. D614G PsVN titers at D15 after a monovalent D614 booster in adults aged between 18 and 55 years were comparable in the adenoviral-vectored and mRNA priming cohorts, but greater in the cohort primed with CoV-2 preS dTM195 AS03 (D614). Following a monovalent D614 booster, seroreactivity to D614G was between 71.2% and 93.1% among priming vaccination subgroups. Following a monovalent D614 booster, seroreactivity to D614G was between 71.2% and 93.1% among priming vaccination subgroups.
Overall, the study findings showed that CoV2 preS dTM-AS03 boosters were safe and induced powerful SARS-CoV-2 neutralizing antibodies against different variants, irrespective of the priming vaccine.
medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.