NVX-CoV2373-induced cellular and humoral immunity towards parental SARS-CoV-2 and VOCs compared to BNT162b2 and mRNA-1273-regimens

• Published in: Journal of clinical virology Vol. 157; p. 105321
• Main Authors: Hielscher, Franziska, Schmidt, Tina, Klemis, Verena, Wilhelm, Alexander, Marx, Stefanie, Abu-Omar, Amina, Ziegler, Laura, Guckelmus, Candida, Urschel, Rebecca, Sester, Urban, Widera, Marek, Sester, Martina
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-12-2022
• Subjects: 2019-nCoV Vaccine mRNA-1273; Antibodies; Antibodies, Neutralizing; Antibodies, Viral; BNT162 Vaccine; Coronavirus; COVID-19; COVID-19 - prevention & control; COVID-19 Vaccines - immunology; Humans; Immunity, Humoral; Immunoglobulin G; Neutralization; SARS-CoV-2; Spike Glycoprotein, Coronavirus; T-cells; Vaccination; Variant of concern; T-cells; IFNγ; TNFα; Vaccination; Antibodies; BNT; IL-2; IQR; VOC; COVID-19; NVX; SEB; SARS-CoV-2; Coronavirus; CTLA-4; Variant of concern; Neutralization
• ISSN: 1386-6532; 1873-5967
• DOI: 10.1016/j.jcv.2022.105321

•NVX-CoV2373 markedly induced spike-specific antibodies and CD4 T cells.•NVX-CoV2373-induced immunity was less pronounced than after mRNA-vaccination.•NVX-CoV2373 poorly induced spike-specific CD8 T cells.•All vaccines elicited similarly poor neutralizing activity towards VOCs.•NVX-CoV2373-induced CD4 T cells cross-reacted towards VOCs from Alpha to Omicron.
The NVX-CoV2373-vaccine has recently been licensed, although knowledge on vaccine-induced humoral and cellular immunity towards the parental strain and variants of concern (VOCs) in comparison to mRNA-regimens is limited.
In this observational study, 66 individuals were recruited to compare immunogenicity and reactogenicity of NVX-CoV2373 with BNT162b2 or mRNA-1273. Vaccine-induced antibodies were analyzed using ELISA and neutralization assays, specific CD4 and CD8 T-cells were characterized based on intracellular cytokine staining using flow-cytometry after antigen-specific stimulation with parental spike or VOCs.
Two doses of NVX-CoV2373 strongly induced anti-spike IgG, although IgG-levels were lower than after vaccination with BNT162b2 or mRNA-1273 (p = 0.006). Regardless of the vaccine and despite different IgG-levels, neutralizing activity towards VOCs was highest for Delta, followed by BA.2 and BA.1. The protein-based vaccine failed to induce any spike-specific CD8 T-cells which were detectable in 3/22 (14%) individuals only. In contrast, spike-specific CD4 T-cells were induced in 18/22 (82%) individuals, although their levels were lower (p<0.001), had lower CTLA-4 expression (p<0.0001) and comprised less multifunctional cells co-expressing IFNγ, TNFα and IL-2 (p = 0.0007). Unlike neutralizing antibodies, NVX-CoV2373-induced CD4 T-cells equally recognized all tested VOCs from Alpha to Omicron. In individuals with a history of infection, one dose of NVX-CoV2373 had similar immunogenicity as two doses in non-infected individuals. The vaccine was overall well tolerated.
NVX-CoV2373 strongly induced spike-specific antibodies and CD4 T-cells, albeit at lower levels as mRNA-regimens. Cross-reactivity of CD4 T-cells towards the parental strain and all tested VOCs may hold promise to protect from severe disease.
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