Safety and immunogenicity of the fourth dose of NVX-CoV2373

In a recent study posted on medrex sib*Preprint server, investigators evaluated the immunogenicity and safety of a fourth allogeneic boost dose of recombinant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). spike protein A vaccine called NVX-CoV2373.

Background

The emergence and rapid spread of SARS-CoV-2 variants, especially Omicron substrains containing mutations that increase the virus’s transmissibility and its ability to resist vaccine protection, could be dramatically reduced. efficacy of licensed vaccine. The efficacy of SARS-CoV-2 ancestral strain-based vaccination against Omicron sublineages is highly dependent on the ability of the vaccine to produce broad cross-reactive antibodies.

About research

In this study, researchers evaluated the immunogenicity and safety of NVX-CoV2373 after a fourth dose.

A subset of healthy adult subjects in an ongoing Phase 2 placebo-controlled NVX-CoV2373 randomized study received two primary vaccination series. He then administered her third and her fourth vaccines of NVX-CoV2373 at six-month intervals. Booster immunizations were delivered intramuscularly at dose levels similar to the first series of vaccinations. This analysis includes only the subject who received her four doses of NVX-CoV2373.

Participants documented systemic and local reactogenicity at the time of vaccination and 6 days after vaccination using an electronic journal. Unsolicited adverse events were recorded during his first 28 days after vaccination. Serious adverse events (SAEs), vaccine-related medically-related adverse events (MAAEs), and adverse events of special interest (AESIs) were recorded through the end of the study. Blood samples were taken for immunogenicity analysis before and after each immunization and on days 0, 35, 189, 217, and 371.

Immune responses were assessed by the following methods. (1) After each administration of NVX-CoV2373 by serum Neutralizing antibody Utilizing validated pseudovirus neutralization assays for ancestral, BA.1, and BA.4/BA.5 variants, (2) using anti-rS IgG assays, and (3) appropriate SARS- Human angiotensin-converting enzyme 2 (ACE2) receptor binding inhibition assay using CoV-2. The software was fed serum neutralization titers recorded after 2, 3, and 4 doses to generate a SARS-CoV-2 antigen map.

result

Of the 1,610 people screened between August 24, 2020 and September 25, 2020, a total of 1,288 subjects were randomized and 1,283 received at least one dose of study vaccine. After 6 months, 207 of the 258 participants originally assigned to receive two doses of NVX-CoV2373 were reset to receive a third dose of NVX-CoV2373 or placebo. Randomized. Approximately 45 patients who received her third dose of NVX-CoV2373 received her fourth dose 6 months later.

Solicited systemic and local reactogenic events were reported after each dose of NVX-CoV2373 was administered. However, these events plateaued or decreased after the fourth vaccination. Incidents of grade 3 or higher reactogenicity often showed a similar trend. Approximately 73% of participants experienced any grade of local reaction such as pain, discomfort, swelling, or erythema, with 19% of individuals reporting Grade 3+ after the fourth dose.

In contrast, 83% of participants reported any grade adverse event and 14% experienced a Grade 3+ event after the third dose. Erythema was experienced more frequently after his fourth dose, with 20% of all grades and 1% of grade 3+ compared with 10% of all grades and 1% of grade 3+ after his third dose. accounted for 15% of the events. Local effects were transient after the fourth vaccination.

After the initial decline observed after the primary vaccination series, administration of the third NVX-CoV2373 vaccine increased anti-recombinant spike (rS) immunoglobulin (Ig)-G titers corresponding to the ancestral strain to 4-fold increase observed. Compared to the decline after the primary series, the titer decreased more slowly after his 3rd dose, whereas the anti-rS IgG titer increased after his 4th dose and was observed after the 3rd dose. equivalent level to that of As the number of vaccine doses increased, the immune response to SARS-CoV-2 Omicron BA.1 followed a similar trend, gradually narrowing the difference in the magnitude of responses to the ancestral and Omicron BA.1 strains. .

A similar pattern was observed between neutralizing and anti-rS IgG titers. His third vaccination with NVXCoV2373 increased his SARS-CoV-2 neutralization titer against the ancestral strain to almost 4.7-fold over the value recorded after the first vaccination. Moreover, the titers induced by the 4th dose were comparable to those after the 3rd dose.

Neutralization titers corresponding to different SARS-CoV-2 variants were assessed using antigenic distance mapping, revealing a decrease in antigenic distance and a fold difference as the number of doses of NVX-CoV2373 increased . The antigenic difference between the Omicron BA.4/5 subvariant and the wild-type strain was 33.5-fold after the primary series of NVX-CoV2373 and 7.1-fold after his third NVX-CoV2373 vaccination Decreased. After the 4th vaccination, the antigenic distance was further shortened by 3.5-fold.

Overall, the study results showed that a fourth dose of NVX-CoV2373 improved immunogenicity without inducing increased reactogenicity. After the fourth dose of NVX-CoV2373, antigen mapping revealed a more homogenous response to SARS-CoV-2 variations, indicating that changes to vaccine formulations may not be justified .

*Important Notices

medRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .