Cellular and humoral immune responses to SARS-CoV2, comparing previously infected individuals who received one vaccine dose to uninfected individuals after three vaccine doses: A case-control study.

Over the last 5 years, the world has been facing the Corona Virus Disease 2019 (COVID-19) pandemic caused by the SARS-CoV2 virus. While vaccination is a leading strategy to control virus spread, it demonstrated an ability to push the virus to evolve and generate vaccine-escape variants. Nevertheless, the official policy in Israel and around the world is vaccination, even in cases of previous SARS-CoV2 infection. Many studies were published regarding vaccination protocols and antibody responses. However, data concerning the differences in humoral and cellular immune response between convalescent individuals who received a single vaccine dose, and SARS-CoV2 naïve vaccinated individuals, are still sparse. In this study we evaluated the humoral and cellular immune response of healthy convalescent individuals who received a single vaccine dose, and compared it with uninfected individuals who received three BNT162b2 mRNA vaccine doses. Humoral immune response was evaluated by testing the ability of donor samples to bind or inhibit the binding of different SARS-CoV2 variants Spike glycoprotein receptor binding domain (RBD) to ACE2. Cellular immunity was tested using flow cytometry to evaluate cytokine production in response to different SARS-CoV2 peptide mixes, including the Wuhan wild-type (WT) Spike glycoprotein (S)-peptide mix, Omicron-specific S-peptide mix and the Membrane (M) protein peptide mix. We show that the ability of convalescent, single-dose vaccinated, donors to bind RBD or inhibit ACE2:RBD interaction was comparable to that of 3-dose vaccinated-only donors, independent of the variant tested. In contrast, when testing cellular response, convalescent individuals showed increased IFNγ staining following WT-S peptide mix stimulation (average of 988.4 ± 687.1 vs 590.2 ± 397.1, p = 0.022 responding IFNγ+ cells per 106 CD4+ cells), and even more enhanced response to M-protein peptide mix (average of 2291 ± 4074.2 vs 239 ± 485.85, p = 0.023 responding IFNγ+ cells per 106 CD4+ cells). This research may provide information for future development of more effective vaccines and vaccination strategies.