In a recent study, researchers determined the T cell response to NVX-CoV2373, an adjuvanted recombinant full-length severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) trimer protein vaccine.
Study
In the present study, researchers collected peripheral blood mononuclear cells (PBMCs) from people who received 5 μg NVX-CoV2373 during phase I/IIa clinical trials in Australia and the US. The phase I arm enrolled individuals aged 18 to 59 years, with the addition of a 60- to 84-year-old stratum in phase II. Specifically, five volunteers were vaccinated with 5 μg of NVX-CoV2373 on day zero and a placebo on day 21. The team isolated four placebo recipients on days zero, seven, and 28. They included samples of only five volunteers collected on days 0 and 7, who received the placebo dose on day 21 in a blinded fashion. The researchers measured SARS-CoV-2 S–specific CD4+ T cells by activation-induced marker (AIM) assay.
Further, they deployed intracellular cytokine staining (ICS) to identify S-specific circulating follicular helper T (cTfh) cells, which helped them assess the functionality of NVX-CoV2373–induced S-specific CD4+ T cell responses (e.g., cytokine production). Furthermore, the researchers examined the relationship between T cell and antibody responses following NVX-CoV2373 vaccination. They estimated the IgG titers via an enzyme-linked immunosorbent assay (ELISA) and SARS-CoV-2 neutralization activity. Finally, the team used microneutralization and human angiotensin-converting enzyme 2 (hACE2) binding inhibition assays to analyze anti-S antibody titers.
Results
Vaccination with NVX-CoV2373 induced a SARS-CoV-2 S–specific CD4+ T cell response as early as seven days after the first vaccination, as measured by AIM assay. This rapid induction of robust T cell responses could be due to increased immunogenicity from the Matrix-M adjuvant in the NVX-CoV2373 vaccine. This adjuvant may be more potent than most adjuvants at inducing CD8+ T cell priming or recalling cross-reactive memory T cells. It has amphiphilic saponins that destabilize the endosomal/lysosomal membrane and facilitate the entry of vaccine antigens into the cytoplasm. This is the first crucial step in cytosolic catabolism and subsequent presentation of major histocompatibility class I (MHC class I) molecules to initiate CD8+ T cell responses.
A substantial cTfh population characterized these T cell responses. A strong, rapid, and sustained cTfh cell response seven days after the first vaccination likely supports the idea of a more effective antibody response. However, the authors did not observe a surge in the scale of the T cell response between the first- and second-vaccination time points. Likewise, these cells had polyfunctional cytokine-producing cells dominated by those producing interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin 2 (IL-2). Notably, a subset of donors also displayed NVX-CoV2373-triggered CD8+ T cell responses.
The authors noted that while CD4+ and CD8+ T cell responses correlated with each other after the first and second rounds of vaccinations, tota; AIM+ detected CD4+ T cells correlated with neutralizing antibody titers. Furthermore, the cytokine data indicated that the NVX-CoV2373 vaccine induced a T helper 1 (Th1) CD4+ T cell response, as reported earlier in other studies. Previous animal model-based studies have reported similar Th1 bias in the presence of Matrix-M adjuvanted vaccines. The cytokine responses increased after the second vaccination, with the increase in polyfunctionality persisting after the second dose, specifying more polarization of the CD4+ T cell response.
Conclusion
Protein subunit vaccines have been poor inducers of CD8+ T cell responses in humans. However, the study data demonstrated that the NVX-CoV2373 vaccine induced modest SARS-CoV-2 S-specific CD8+ T cell responses in a subset of participants. ICS results fetched similar results, with IFN-γ+ CD8+ T cells detected after two rounds of the NVX-CoV2373 vaccination.
Although less polyfunctional, several donors developed multifunctional CD8+ T cell responses following NVX-CoV2373 vaccination. As S-specific CD8+ T cell responses correlated with CD4+ T cell responses, the observed CD8+ T cell response likely depended on the CD4+ T cell response. Further studies with larger cohorts of seropositive and seronegative vaccinees are warranted to validate the study findings.
Source:
https://www.news-medical.net/news/20221005/Novel-protein-vaccine-NVX-CoV2373-triggered-functional-T-cell-responses-to-SARS-CoV-2.aspx