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

The pandemic with coronavirus disease 2019 (COVID-19) started in December 2019 in Wuhan, China, with the spread of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This communicable disease has lasted ever since and culminated 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 / ShutterstockExamination: 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

Several vaccines against SARS-CoV-2 spike (S) protein have been proposed using a variety of technologies – mRNA-1273, BNT162b2, AD26.COV2.S and AZD1222, with approximately 8.81 billion doses delivered to date. While real-world clinical trials and evidence show high success rates for these vaccines in the prevention of serious illness and death due to COVID-19, opportunities for diminishing efficacy following immunization programs were projected.

To address the problems, mutants or variants of SARS-CoV-2 have emerged with altered S-protein receptor binding domain (RBD), which may partially avoid neutralization in vaccinated individuals. The World Health Organization (WHO) has identified five of these variants as variants of concern (VOC) – B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) and latest B.1.1.529 (Omicron). New SARS-CoV-2 mutations and evidence of diminishing vaccine efficacy pose significant challenges for 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 can alleviate risks by boosting and expanding the immune response shown with initial vaccination programs.

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

A new study published on medRxiv * the 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 in which 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, approximately 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 selected variations were performed to determine 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 study for both the original vaccine strain and recent SARS-CoV-2 variations such as Alpha, Beta and Delta.

Fund

The results showed that IgG titers in the parent strain were approximately 34 times greater on day 217 than on day 189 before the booster, while neutralizing antibody titers increased approx. 96 times after the booster. Both IgG and MN titers were> 4-fold after the booster than after the initial two-dose series on day 35, which is significant as 35th daytime titers are usually high.

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

Although the overall incidence of Beta has recently dropped to 1% from a record high of 8% in April 2021, antibody responses to this variant remain interesting due to the E484K mutation observed in this version. E484K has been associated with significant decreases in neutralization titers for vaccines, monoclonal antibodies, and convalescent sera. The mutation continues in the SARS-CoV-2 P.1, P.2 and Mu variants.

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

The prevalence of both local and systemic reactogenicity was greater after 6 months of booster dose compared to previous doses.

The frequency of grade 3 or higher events, on the other hand, remained very low, with only fatigue reported by more than 10% of individuals. In total, five grade 4 local and systemic adverse reactions were reported along with an adverse event of vaccine hypersensitivity episode, however, in the same individual in the active booster group. The severity of the hypersensitivity episode was considered mild. All of the participant’s symptoms – pain, soreness, headache, malaise and muscle discomfort, disappeared within six days.

The estimated reactogenicity rates after the third dose of NVX-CoV2373 were similar to those seen with a booster dose of the Pfizer / BioNtech and Moderna vaccines, but higher compared to the Oxford / AstraZeneca vaccine. However, the number of unintended side effects after the booster was higher in vaccine users than in placebo recipients – but was mild or moderate in severity. Serious adverse reactions were less frequent after booster dose and were evenly distributed between 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 use of the vaccine in booster regimens.

*Important message

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered as crucial, guide clinical practice / health-related behavior or be treated as established information.

.

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

The pandemic with coronavirus disease 2019 (COVID-19) started in December 2019 in Wuhan, China, with the spread of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This communicable disease has lasted ever since and culminated 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 / ShutterstockExamination: 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

Several vaccines against SARS-CoV-2 spike (S) protein have been proposed using a variety of technologies – mRNA-1273, BNT162b2, AD26.COV2.S and AZD1222, with approximately 8.81 billion doses delivered to date. While real-world clinical trials and evidence show high success rates for these vaccines in the prevention of serious illness and death due to COVID-19, opportunities for diminishing efficacy following immunization programs were projected.

To address the problems, mutants or variants of SARS-CoV-2 have emerged with altered S-protein receptor binding domain (RBD), which may partially avoid neutralization in vaccinated individuals. The World Health Organization (WHO) has identified five of these variants as variants of concern (VOC) – B.1.1.7 (Alpha), B.1.351 (Beta), P.1 (Gamma), B.1.617.2 (Delta) and latest B.1.1.529 (Omicron). New SARS-CoV-2 mutations and evidence of diminishing vaccine efficacy pose significant challenges for 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 can alleviate risks by boosting and expanding the immune response shown with initial vaccination programs.

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

A new study published on medRxiv * the 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 in which 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, approximately 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 selected variations were performed to determine 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 study for both the original vaccine strain and recent SARS-CoV-2 variations such as Alpha, Beta and Delta.

Fund

The results showed that IgG titers in the parent strain were approximately 34 times greater on day 217 than on day 189 before the booster, while neutralizing antibody titers increased approx. 96 times after the booster. Both IgG and MN titers were> 4-fold after the booster than after the initial two-dose series on day 35, which is significant as 35th daytime titers are usually high.

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

Although the overall incidence of Beta has recently dropped to 1% from a record high of 8% in April 2021, antibody responses to this variant remain interesting due to the E484K mutation observed in this version. E484K has been associated with significant decreases in neutralization titers for vaccines, monoclonal antibodies, and convalescent sera. The mutation continues in the SARS-CoV-2 P.1, P.2 and Mu variants.

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

The prevalence of both local and systemic reactogenicity was greater after 6 months of booster dose compared to previous doses.

The frequency of grade 3 or higher events, on the other hand, remained very low, with only fatigue reported by more than 10% of individuals. In total, five grade 4 local and systemic adverse reactions were reported along with an adverse event of vaccine hypersensitivity episode, however, in the same individual in the active booster group. The severity of the hypersensitivity episode was considered mild. All of the participant’s symptoms – pain, soreness, headache, malaise and muscle discomfort, disappeared within six days.

The estimated reactogenicity rates after the third dose of NVX-CoV2373 were similar to those seen with a booster dose of the Pfizer / BioNtech and Moderna vaccines, but higher compared to the Oxford / AstraZeneca vaccine. However, the number of unintended side effects after the booster was higher in vaccine users than in placebo recipients – but was mild or moderate in severity. Serious adverse reactions were less frequent after booster dose and were evenly distributed between 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 use of the vaccine in booster regimens.

*Important message

medRxiv publishes preliminary scientific reports that are not peer-reviewed and therefore should not be considered as crucial, guide clinical practice / health-related behavior or be treated as established information.

.

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