SARS-CoV-2 mRNA vaccine BNT162b2 triggers a consistent cross-variant humoral and cellular response

Abstract

As the SARS-CoV-2 pandemic continues to rage worldwide, the emergence of numerous variants of concern (VOC) represents a challenge for the vaccinal protective efficacy and the reliability of commercially available high-throughput immunoassays. Our study demonstrates the administration of two doses of the BNT162b2 vaccine that elicited a robust SARS-CoV-2-specific immune response which was assessed up to 3 months after full vaccination in a cohort of 37 health care workers (HCWs). SARS-CoV-2-specific antibody response, evaluated by four commercially available chemiluminescence immunoassays (CLIA), was qualitatively consistent with the results provided by the gold-standard in vitro neutralization assay (NTA). However, we could not observe a correlation between the quantity of the antibody detected by CLIA assays and their neutralizing activity tested by NTA. Almost all subjects developed a SARS-CoV-2-specific T-cell response. Moreover, vaccinated HCWs developed a similar protective neutralizing antibodies response against the EU (B.1), Alpha (B.1.1.7), Gamma (P.1), and Eta (B.1.525) SARS-CoV-2 variants, while Beta (B.1.351) and Delta (B.1.617.2) strains displayed a consistent partial immune evasion. These results underline the importance of a solid vaccine-elicited immune response and a robust antibody titre. We believe that these relevant results should be taken into consideration in the definition of future vaccinal strategies.

Keywords: Humoral response; SARS-CoV-2 bnt162b2 mRNA vaccine; SARS-CoV-2 variants of concern; T-cell mediated respone.

Figure 1.

Synoptic representation of the study design with timing and type of analyses.

Figure 2.

Humoral response. Panel (A) Anti-SARS-CoV-2 specific antibody titre overtime, quantified by four different CLIA methods and by neutralization assay (NTA). Panel (B) Percentage of subjects detected positive to anti-SARS-CoV-2 specific antibodies overtime, quantified by four different CLIA methods and by neutralization assay (NTA). Time of vaccinations is represented by vertical dashed lines.

Figure 3.

Cellular response. Panel (A) T-cell mediated response measured by QuantiFERON assay related to CD4+ T-cell only (black) or CD4+ and CD8+ T-cells together (grey). Data refer to T6 and are expressed as international unit per millilitre (IU/ml); the cut-off is 0.15 IU/ml. Panel (B and C) correlation between the neutralization assay (NTA) and cellular CD4+ and CD4++CD8+ T-cells response, respectively. Panel (D and E) correlation between anti-SARS-CoV-2 specific antibodies measured by YHLO i-Flash and cellular CD4+ and CD4++CD8+ T-cells response, respectively. The correlation with the quantification of anti-SARS-CoV-2 specific antibodies measured by the other methods is depicted in figure S2.

Figure 4.

SARS-CoV-2 variants of concern (VOC). Panel (A) Neutralization assay (NTA) performed at T5 on the SARS-CoV-2 lineage B.1 (EU) and 5 VOCs, α-η. Panels (B-F) Comparison between the EU variant and the VOCs α-η, respectively. Lines connect the NTAs of each individual subject.

Figure 5.

Neutralization assays correlations. Panel (A–E) NTA correlation between the EU variant and the VOCs, respectively, performed at T5. The other correlations between variants are depicted in figure S3.

Figure 6.

Correlation between anti-SARS-CoV-2 specific antibodies and neutralization assays (NTA). Panel (A–F) correlation between anti-SARS-CoV-2 specific antibodies measured by YHLO i-Flash and the NTA performed on the EU variants and the VOCs, respectively, performed at T5. The correlation with the quantification of anti-SARS-CoV-2 specific antibodies measured by the other methods is depicted in figure S3.