Study: Trial of SARS-CoV-2 Variant Vaccine Boosters: Preliminary analyses. Image credit: WESTOCK PRODUCTIONS/Shutterstock
Record
SARS-CoV-2 has resulted in more than 557 million infections and more than 6.3 million deaths worldwide, with more than 1 million deaths in the United States (US). SARS-CoV-2 vaccines fully approved or authorized for emergency use in the US are safe and highly effective against serious disease. However, vaccine-mediated immunity against symptomatic CoV disease 2019 (COVID-19) wanes over time. In addition, several SARS-CoV-2 variants of concern (VOCs) have now been identified, including Beta (B.1.351), Delta (B.1.617.2), Omicron BA.1 (B.1.1.529), Omicron BA . 4/BA.5 and BA.2.12.1 sublines, all of which are characterized by mutations in the spike protein (S) receptor binding domain (RBD). These VOCs increase the chances of explosive infections. While more booster doses of existing COVID-19 vaccines, which target the S protein of SARS-CoV-2 prototype strain Wuhan-1, may increase vaccine efficacy against VOCs in the near future, variant-specific vaccines may be required for long time – Sustained and enhanced protection against both known and emerging WPOs.
About this study
The present study evaluated the immunogenicity and safety of SARS-CoV-2 vaccine variants. The team described the range, magnitude and landscapes of the initial neutralizing antibody response after the second booster vaccination with experimental variant-specific COVID-19 vaccines, indicative of the varied SARS-CoV-2 immune context seen in the general public. The current randomized, open-label, phase II trial included healthy adults who had previously received an initial course of treatment for COVID-19 and a single booster vaccination. Eligible subjects were randomly assigned to the six vaccination groups with doses of 50 μg of Moderna SARS-CoV-2 messenger ribonucleic acid (mRNA). These cohorts were: Beta+Omicron BA.1 (one or two doses), Omicron BA.1 monovalent, Delta+Omicron BA.1, Prototype (mRNA-1273), and Prototype+Omicron BA.1. Neutralizing antibody titers or infectious dose 50 (ID50) were assessed for Beta, Delta, D614G and Omicron BA.1 variant and Omicron BA.4/BA.5 and BA.2.12.1 sub-variants 15 days after inoculation. Additionally, on Day 15, a subset of samples from individuals uninfected with SARS-CoV-2 in four arms were tested in a separate laboratory for neutralizing antibody titers to D614G and Omicron BA.2.12.2, BA.1, and BA.4 Subvariants /BA.5.
Results and conclusions
The study data showed that 597 volunteers were randomly selected and vaccinated between March 30 and May 6, 2022. The average age of the subjects was 53 and 20% had already been infected with SARS-CoV-2. Each vaccine produced strong serological responses to SARS-CoV-2 strain D614G, Delta, Omicron BA.1 and Beta VOCs and was well tolerated and safe. In all groups, titers against D614G were higher than VOCs, comparable across age groups, and maximal in those with a prior history of COVID-19. All arm day 15 ID50 neutralization titers to D614G exceeded those associated with the previously reported protection in a previous Moderna mRNA-1273 efficacy study. Neutralizing potency against Omicron BA.1 improved with repeated doses of mRNA vaccines, although titers remained three- to eightfold lower than neutralizing the D614G strain. Omicron-containing vaccines showed a higher serological response against the Omicron BA.1 variant than the Prototype. Although measurable titers were found in 98.8% of volunteers tested, all vaccine options produced titers to the Omicron BA.4/BA.5 subvariants that were approximately one-third lower than those of BA.1. Given the small number of samples analyzed against the Omicron BA.4/BA.5 sublines, the scientists could not conclude that vaccines harboring Omicron BA.1 would provide serological benefit exclusively for these sublines. Interestingly, Omicron BA.1-containing vaccines induced neutralizing GMT antibodies directed at BA.4/BA.5 at Day 15, which were higher than the titers produced by the Prototype vaccine. Furthermore, the authors noted that the observed antibody landscapes strongly justify the use of SARS-CoV-2 variants in booster vaccinations. The antigenic landscape increases shortly after vaccination. Notably, it was leveled more by Omicron BA.1 + Prototype, Omicron BA.1 monovalent and Omicron BA.1 + Beta vaccines than by Prototype vaccine. This conclusion implies that variant inoculants containing Omicron may elicit higher neutralizing antibody titers against impending VOCs if exposed in close proximity to Omicron BA.1. In addition, all landscapes fell least over Omicron BA.4/BA.5, indicating that protection was minimal in this antigenic region. Overall, the study findings showed that relative to the SARS-CoV-2 Prototype vaccine, Omicron-containing vaccinations showed higher Omicron BA.1 titers. Furthermore, it showed that for all SARS-CoV-2 variant vaccine options, titers to Omicron BA.4/BA.5 were lower than to BA.1.
*Important note
medRxiv publishes preliminary scientific reports that have not been peer-reviewed and therefore should not be considered definitive, guide clinical practice/health-related behavior, or be treated as established information.
