Immune responses in SARS-CoV-1 survivors after COVID-19 vaccination

recently cell report In a journal study, researchers evaluated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine-induced immune responses in SARS survivors.

study: SARS-CoV-2 vaccine-induced antibody and T cell responses in SARS-CoV-1 survivors. Image credit: creativeneko/Shutterstock.com

Background

SARS-CoV-1, the causative agent of the 2002 epidemic, is a beta-CoV of the coronavirus family. SARS-CoV-1 infection induces humoral and cell-mediated immune responses. Antibody responses can persist for 2–3 years after infection, and specific memory B cells (MBC) decline to undetectable levels by 6 years.

In contrast, SARS-CoV-1 nucleocapsid (N)-specific memory T cell responses can still be detected after 17 years. These memory T lymphocytes show cross-reactivity with the SARS-CoV-2 N protein.

Increasing evidence points to SARS-CoV-2 cross-reactive memory T cells in SARS-CoV-2-uninfected individuals. Several reports have also shown cross-reactivity between SARS-CoV-2-specific T cells and T cells specific for animal beta-CoV and human cold-CoV.

One study found that over 90% of healthy adults have immunoglobulin G (IgG) specific for all human cold CoVs. However, whether the coronavirus disease 2019 (COVID-19) vaccine enhances pre-existing cross-reactive memory T cell responses remains elusive.

Survey results

In the current study, researchers analyzed SARS-CoV-2-specific antibody and T-cell responses after a single dose of the COVID-19 vaccine (Ad5-nCoV) in people who survived infection with SARS-CoV-1. increase. A total of 25 SARS survivors were enrolled in the current study between June 2020 and July 2020.

Twenty study participants received the Ad5-nCoV vaccine in July 2021.

Additionally, 18 naive healthy individuals (NHI) who received the Ad5-nCoV vaccine were also enrolled in the current study. Ten cryopreserved specimens of peripheral blood mononuclear cells (PBMC) and serum from healthy donors before September 2019 were used as controls.

Researchers measured neutralizing antibody (nAb) levels against SARS-CoV-2 Wuhan-Hu-1 (WA), alpha, beta, gamma, delta, and omicron variants.

Most SARS-CoV-1 survivors had nAb against SARS-CoV-1, but none had nAb against SARS-CoV-2 before vaccination. After vaccination, 13 of her 23 survivors neutralized SARS-CoV-2 WA1. However, neutralization against Omicron subvariants BA.1, BA.2, BA.2.12.1, and BA.4/5 was attenuated. Nevertheless, nAb geometric mean titers (GMT) were higher against SARS-CoV-1 than against WA1.

One-third of NHIs had detectable nAb against WA1 after vaccination, and there were no significant differences in GMT among SARS-CoV-2 WA1, variants, and SARS-CoV-1. Only SARS-CoV-1 survivors who received the Ad5-nCoV vaccine had nAbs against all viruses tested.

Because antibody responses between vaccinated SARS survivors and NHIs were comparable, researchers investigated whether the same applies to T-cell responses. To this end, SARS-CoV-2 spike-specific T cell responses were determined using intracellular cytokine staining (ICS), activation-induced markers (AIM), and enzyme-linked immunosorbent spot (ELISpot) assays. it was done.

ELISpot assays showed that post-vaccination SARS-CoV-2 spike-specific interferon-γ (IFN-γ)-secreting T cell levels were significantly higher in NHI and SARS survivors than in healthy controls. was shown to be comparable to

All survivors and 16 NHIs had detectable levels of IFN-γ-secreting spike-specific T cells. SARS-CoV-2 spike-specific AIM⁺ Differentiation cluster 4 positive (CD4⁺) T cells were detected in 17 SARS survivors and 16 NHI, with median frequencies similar but significantly higher than controls. I observed a similar pattern of⁺ CD8⁺ T cells.

ICS assay revealed the presence of SARS-CoV-2 spike-specific IFN-γ⁺ CD4⁺ T cells The median frequency was significantly higher than controls in 75% of SARS survivors and 66% of NHIs. Similarly, spike-specific IFN-γ was detected in 80% of SARS-CoV-1 survivors and 38.1% of NHIs.⁺ CD8⁺ T cells. SARS-CoV-1 survivors had significantly higher frequencies than controls, but NHIs and controls had similar frequencies.

Finally, the authors evaluated whether Ad5-nCoV vaccination resulted in stronger and stronger SARS-CoV-1-specific T-cell responses in SARS-CoV-1 survivors. Taken together, 81% of SARS survivors and 40% of NHIs had SARS-CoV-1 spike-specific IFN-γ-secreting T cells as determined by ELISpot assays.

More than 80% of SARS-CoV-1 survivors had SARS-CoV-1 spike-specific AIM⁺ CD4⁺ and CD8⁺ T cells and IFN-γ⁺ CD4⁺ T cells, whereas about 60% of SARS-CoV-1 survivors had detectable IFN-γ⁺ CD8⁺ T cells.

Conclusion

Ad5-nCoV vaccination of SARS-CoV-1 survivors boosted nAb against SARS-CoV-1, but the magnitude and level of nAb against SARS-CoV-2 were low. Nonetheless, vaccination of a SARS-CoV-1 survivor and her NHI induced a specific T-cell response to his SARS-CoV-2 variant six months after vaccination. It suggests that vaccination is insufficient to increase the breadth and lifespan of SARS-CoV-2. It produces a specific antibody response but leads to a prolonged T cell response.

Taken together, the results of this study demonstrate that SARS-CoV-1 survivors and NHIs display comparable T-cell and antibody responses to SARS-CoV-2 after vaccination.