Exploring immunogenicity and safety after a homologous booster dose of SARS-CoV-2 recombinant spike protein vaccine

The coronavirus disease 2019 (COVID-19) pandemic started in December 2019 in Wuhan, China, with the spread of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This communicable disease has persisted ever since, culminating in millions of deaths worldwide.

Study: Immunogenicity and Safety Following a Homologous Booster Dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373): A Phase 2 Randomized Placebo-Controlled Trial. Image Credit: Prostock-studio/Shutterstock

Numerous vaccines against the SARS-CoV-2 spike (S) protein have been proposed utilizing a variety of technologies – mRNA-1273, BNT162b2, AD26.COV2.S and AZD1222, with approximately 8.81 billion doses provided to date. Whilst clinical studies and real-world evidence demonstrate high success rates of these vaccines in preventing severe disease and death by COVID-19, possibilities of waning effectiveness post-immunization programs were projected.

To add up to the woes, mutants or variants of SARS-CoV-2 have emerged with altered S protein receptor-binding domain (RBD), which can partially avoid neutralization in vaccinated individuals. The world Health Organization (WHO) has designated five of these variants as variants of concern (VOCs) – B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) and, most recently, B.1.1.529 (Omicron). Emerging SARS-CoV-2 mutations and evidence of diminishing vaccine efficacy pose substantial challenges to COVID-19 pandemic control.

The development of variant-specific vaccinations, as well as the use of homologous vaccine booster doses, are being researched as promising ways to improve protection against COVID-19. Booster doses of SARS-CoV-2 vaccinations could alleviate risks by increasing and broadening the immune responses exhibited with initial vaccination programs.

Novavax has designed a SARS-CoV-2 recombinant S protein nanoparticle vaccine (SARSCoV-2 rS), which consists of the full-length, pre-fusion trimers of the ancestral SARS-CoV-2 S glycoprotein co-formulated with a saponin-based adjuvant, Matrix-M^TM (NVX-CoV2373). The vaccination effectiveness (VE) of NVX-CoV2373 against mild, moderate, or severe COVID19 was established in two, phase III randomized, placebo-controlled clinical studies of healthy and medically stable adult participants, using a two-dose series.

A new study released on the medRxiv* preprint server sought to investigate immunogenicity and safety following a homologous Booster Dose of a SARS-CoV-2 recombinant spike protein vaccine (NVX-CoV2373).

The study

This was a phase II randomized placebo-controlled trial wherein a single booster dose of a SARS-CoV-2 recombinant spike protein vaccine with NVX-CoV2373 adjuvant was administered to healthy adult participants aged 18-84 years, about six months after their first two vaccination doses.

Assays for immunoglobulin (IgG), neutralization assay (MN₅₀) and a functional hACE2 receptor binding inhibition assay against the original SARS-CoV-2 strain and select variations were performed to determine the safety and immunogenicity characteristics (B.1.351 [Beta], B.1.1.7 [Alpha], B.1.617.2 [Delta], and B.1.1.529 [Omicron]). The antibody responses to the booster were evaluated in the current investigation for both the original vaccine strain and recent SARS-CoV-2 variations such as Alpha, Beta and Delta.

Findings

The findings showed that IgG titers in the ancestral strain were roughly 34-fold greater on day-217 than on day-189 before the booster while neutralizing antibody titers increased approximately 96-fold after the booster. Both IgG and MN titers were >4-fold following the booster than after the original two-dose series at day- 35, which is significant as the 35^th day titers are usually high.

Further, after the booster dose, IgG and MN antibody titers in the Beta variant increased 40- to 50-fold and IgG titers were roughly 4-fold greater than those reported in the ancestral strain after the initial immunization series. Unlike IgG, MN₅₀ GMTs for the Beta variant were decreased post-booster compared to that of the ancestral strain after the first immunization series, consistent with the documented decreased neutralizing responses for this variant.

Although the overall prevalence of Beta has recently dropped to 1% from an all-time high of 8% in April 2021, antibody responses to this variant remain of interest due to the E484K mutation observed in this version. E484K has been linked to significant declines in neutralization titers for vaccines, monoclonal antibodies and convalescent sera. The mutation persists in the SARS-CoV-2 P.1, P.2 and Mu variants.

These outcomes of significantly increased antibody titers after boosting are significant because they come at a time when SARS-CoV-2 vaccine booster doses are being widely considered or implemented by a number of countries to counteract the waning antibody titers and significantly reduced efficacy of approved vaccines.

The prevalence of both local and systemic reactogenicity was greater after the 6-month booster dose compared to prior doses.

The incidence of Grade 3 or higher events, on the other hand, remained very low, with only weariness being reported by more than 10% of individuals. Overall, five Grade 4 local and systemic adverse events along with an adverse event of vaccine hypersensitivity episode were reported, although in the same individual in the active booster group. The severity of the hypersensitivity episode was deemed mild. All of the participant's symptoms – pain, tenderness, headache, malaise and muscle discomfort, subsided within six days.

The reactogenicity rates estimated after the third dose of NVX-CoV2373 seemed similar to those seen with a booster dose of the Pfizer/BioNtech and Moderna vaccines, but higher when compared to the Oxford/AstraZeneca vaccine. However, the number of unintentional adverse events after the booster was higher in vaccination users than in placebo receivers––but were mild or moderate in severity. Serious adverse events were less frequent after the booster dose and were evenly distributed among the vaccine and placebo groups.

Implications

In summary, a single booster dose of NVX-CoV2373 given approximately six months after the primary series induced significant increases in humoral antibodies, while also exhibiting an acceptable safety profile. These data justify the vaccine's usage in booster regimens.

*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.

Written by

Nidhi Saha

I am a medical content writer and editor. My interests lie in public health awareness and medical communication. I have worked as a clinical dentist and as a consultant research writer in an Indian medical publishing house. It is my constant endeavor is to update knowledge on newer treatment modalities relating to various medical fields. I have also aided in proofreading and publication of manuscripts in accredited medical journals. I like to sketch, read and listen to music in my leisure time.