What is the impact of SARS-CoV-2 variant booster vaccinations?

By Shanet Susan AlexJul 19 2022Reviewed by Aimee Molineux

In a recent study posted to the medRxiv* preprint server, researchers conducted preliminary assessments of booster vaccinating with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant vaccines.

*Important notice: medRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Background 

SARS-CoV-2 has led to over 557 million infections and more than 6.3 million deaths globally, with more than 1 million mortalities in the United States (US). The SARS-CoV-2 vaccinations fully approved or authorized for emergency use in the US are safe and highly efficacious against severe illness. However, vaccine-imparted immunity against symptomatic Coronavirus disease 2019 (COVID-19) diminishes with time.

Moreover, various 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 sublineages, which are all characterized by mutations in the spike (S) protein receptor-binding domain (RBD). These VOCs raise the chances of breakthrough infections.

While more booster doses of the existing COVID-19 vaccines, which target the S protein of the SARS-CoV-2 prototype Wuhan-1 strain, might increase vaccine efficacy against VOCs in the near run, variant-specific vaccines might be required for long-lasting and enhanced protection against both known and arising VOCs.

About this study

The present study assessed the immunogenicity and safety of SARS-CoV-2 variant vaccines. The team outlined the breadth, magnitude, and landscapes of the initial neutralizing antibody reaction after the second booster vaccination with experimental variant-specific COVID-19 vaccines indicative of the varied SARS-CoV-2 immunologic context observed among the general public.

The current phase II randomized, open-label trial included healthy adults who had previously received a COVID-19 initial course and a single boost vaccination. Eligible subjects were assigned randomly to the six 50 µg dose Moderna SARS-CoV-2 messenger ribonucleic acid (mRNA) vaccination groups. 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.

Neutralization antibody titers or infectious dose 50 (ID50) were evaluated for Beta, Delta, D614G, and Omicron BA.1 variant and Omicron BA.4/BA.5 and BA.2.12.1 subvariants 15 days following vaccination. In addition, on day 15, a subset of samples from non-SARS-CoV-2-infected individuals in four arms was examined in a separate lab for neutralizing antibody titers to D614G and Omicron BA.2.12.2, BA.1, and BA.4/BA.5 subvariants.

Results and conclusions

The study data indicated that 597 volunteers were chosen randomly and vaccinated between 30 March and 6 May 2022. The subjects' average age was 53, and 20% had already contracted SARS-CoV-2. Each vaccine produced strong serologic reactions to the SARS-CoV-2 D614G strain, the Delta, Omicron BA.1, and Beta VOCs and was well-tolerated and safe.

In all groups, titers against D614G were higher relative to the VOCs, comparable throughout age groups, and were highest in those with previous COVID-19 history. All arms' day 15 ID50 neutralization titers towards D614G surpassed those connected with the earliest reported protection in a prior Moderna mRNA-1273 effectiveness study.

The neutralizing potency against Omicron BA.1 was improved with repeated doses of mRNA vaccines, although the titers remained three to eight times lower than the neutralization of the D614G strain. Omicron-harboring vaccines showed a higher serological reaction against the Omicron BA.1 variant than the prototype.

Even though measurable titers were found in 98.8% of volunteers screened, all vaccine options produced titers to the Omicron BA.4/BA.5 subvariants that were around one-third lower than those to BA.1. Given the small number of samples analyzed against the Omicron BA.4/BA.5 sublineages, the scientists were not able to conclude that Omicron BA.1-harboring vaccines would confer a serologic benefit exclusively for these sublineages. Interestingly, vaccines comprising Omicron BA.1 induce neutralizing antibodies GMT addressing BA.4/BA.5 at Day 15, which were higher than titers produced by the prototype vaccine.

Moreover, the authors noted that the observed antibody landscapes strongly justify using SARS-CoV-2 variants in booster vaccinations. The antigenic landscape elevates shortly after vaccination. Remarkably, it was flattened more by the Omicron BA.1 + Prototype, Omicron BA.1 monovalent, and Omicron BA.1 + Beta vaccines than by the prototype vaccine. This inference implies that Omicron-containing variant vaccinations might elicit higher neutralizing antibody titers against forthcoming VOCs if they appear close to Omicron BA.1. Furthermore, all landscapes fall the least over Omicron BA.4/BA.5, indicating that the protection was the least in this antigenic region.

Overall, the study findings showed that relative to the SARS-CoV-2 prototype vaccine, Omicron-containing vaccinations exhibited higher Omicron BA.1 titers. Further, it showed that for all SARS-CoV-2 variant vaccine options, titers towards Omicron BA.4/BA.5 were less than against BA.1.

*Important notice: 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.