Infection with SARS-CoV-2 primes immunological memory in human nasal-associated lymphoid tissue

Abstract

Background The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has resulted in considerable morbidity and mortality in humans. Little is known regarding the development of immunological memory following SARS-CoV-2 infection or whether immunological memory can provide long-lasting protection against reinfection. Urgent need for vaccines is a considerable issue for all governments worldwide. Methods A total of 39 patients were recruited in this study. Tonsillar mononuclear cells (MNCs) were co-cultured in RPMI medium and stimulated with the full-length SARS-CoV-2 spike protein in the presence and absence of a CpG-DNA adjuvant. An enzyme-linked immunosorbent assay (ELISA) was utilised to measure the specific antibody response to the spike protein in the cell culture supernatants. Results The SARS-CoV-2 spike protein primed a potent memory B cell-mediated immune response in nasal-associated lymphoid tissue (NALT) from patients previously infected with the virus. Additionally, spike protein combined with the CpG-DNA adjuvant induced a significantly increased level of specific anti-spike protein IgG antibody compared with the spike protein alone ( p < 0.0001, n = 24). We also showed a strong positive correlation between the specific anti-spike protein IgG antibody level in a serum samples and that produced by MNCs derived from the same COVID-19-recovered patients following stimulation ( r = 0.76, p = 0.0002, n = 24). Conclusion Individuals with serological evidence of previous SARS-CoV-2 exposure showed a significant anti-spike protein-specific memory humoral immune response to the viral spike protein upon stimulation. Additionally, our results demonstrated the functional response of NALT-derived MNCs to the viral spike protein. CpG-DNA adjuvant combined with spike protein induced significantly stronger humoral immune responses than the spike protein alone. These data indicate that the S protein antigen combined with CpG-DNA adjuvant could be used as a future vaccine candidate.

Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines

“…In animal models, antibodies alone are sufficient to protect against SARS-CoV-2 infection (19). By stimulating mononuclear cells isolated from the tonsil of SARS-CoV-2 infected individuals, Mahallawi et al confirmed that the SARS-CoV-2 spike primed potent specific memory B cells in nasal associated lymphoid tissue (NALT) (20). The mRNA vaccine, which induces nasal antibody in unexposed subjects, may have the potential to induce the recall of NALT specific memory B cells, thus the increase in nasal Ig levels in the NELF of the recovered subjects receiving their booster.…”

Live attenuated influenza vaccine induces broadly cross-reactive mucosal antibody responses to different influenza strains in tonsils

“…The tonsils were immediately kept in HANKS transport medium (Sigma-Aldrich) following the operation. Mononuclear cells were isolated using Ficoll density centrifugation following methods described previously ( Mahallawi and Aljeraisi, 2021a , Mahallawi and Aljeraisi, 2021b ). In brief, tonsils were processed within one hour of surgery.…”

Comparison of the mucosal and systemic antibody responses in Covid-19 recovered patients with one dose of mRNA vaccine and unexposed subjects with three doses of mRNA vaccines

“…In animal models, antibodies alone are sufficient to protect ag SARS-CoV-2 infection [19]. By stimulating mononuclear cells isolated from the tons SARS-CoV-2 infected individuals, Mahallawi et al confirmed that the SARS-CoV-2 spike pr potent specific memory B cells in nasal associated lymphoid tissue (NALT) [20]. The mRNA cine, which induces nasal antibody in unexposed subjects, may have the potential to induce recall of NALT specific memory B cells, thus the increase in nasal Ig levels in the NELF o recovered subjects receiving their booster.…”