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

In a recent cell reports In a journal study, researchers examined the vaccine-induced immune response in SARS survivors caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

To learn: SARS-CoV-2 vaccine-induced antibody and T-cell response in SARS-CoV-1 survivors. Credit: creativeneko / Shutterstock.com

background

SARS-CoV-1, the causative agent of the 2002 epidemic, is a beta-CoV of the Coronaviridae family. SARS-CoV-1 infection triggers humoral and cellular immune responses. Antibody responses can persist two to three years after infection, and specific memory B cells (MBCs) decline to undetectable levels after six years.

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

Mounting evidence shows SARS-CoV-2 cross-reactive memory T cells in SARS-CoV-2 naïve individuals. Several reports also indicate cross-reactivity between SARS-CoV-2 specific T cells and the T cells specific for animal beta-CoVs and human cold-CoVs.

One study found that more than 90% of healthy adults have immunoglobulin G (IgG), which is specific to all human cold-CoVs. However, whether vaccines against coronavirus disease 2019 (COVID-19) enhance preexisting cross-reactive memory T-cell responses remains elusive.

study results

In the present study, researchers are analyzing SARS-CoV-2-specific antibody and T-cell responses after a dose of a COVID-19 vaccine (Ad5-nCoV) in those who survived infection with SARS-CoV-1 . 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. In addition, three vaccinated survivors were enrolled in the study approximately six months after vaccination.

In addition, 18 naïve healthy individuals (NHIs) who received the Ad5-nCoV vaccine were also included in the current study. Ten cryopreserved samples of peripheral blood mononuclear cells (PBMCs) and serum collected prior to September 2019 from healthy donors served as controls.

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

Although most SARS-CoV-1 survivors had nAbs to SARS-CoV-1, none had nAbs to SARS-CoV-2 prior to vaccination. After vaccination, 13 of these 23 survivors neutralized SARS-CoV-2 WA1; however, the neutralization against the Omicron subvariants BA.1, BA.2, BA.2.12.1 and BA.4/5 has been toned down. Nonetheless, the geometric mean titers (GMTs) of nAb against SARS-CoV-1 were higher than against WA1.

One-third of NHIs had detectable nAbs against WA1 post-vaccination, with no significant differences in GMTs between SARS-CoV-2 WA1, variants and SARS-CoV-1. Only Ad5-nCoV-vaccinated SARS-CoV-1 survivors had nAbs against all viruses tested.

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

The ELISpot assay showed comparable post-vaccination median levels of SARS-CoV-2 spike-specific interferon-gamma (IFN-γ)-secreting T cells in NHIs and SARS survivors, albeit significantly higher than in healthy controls.

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 NHIs, with comparable mean frequencies but significantly higher than controls. The researchers observed a similar pattern of SARS-CoV-2 spike-specific AIM⁺ CD8⁺ T cells.

The ICS assay demonstrated the presence of SARS-CoV-2 spike-specific IFN-γ⁺ CD4⁺ T cells in 75% of SARS survivors and 66% of NHIs, with significantly higher mean frequencies than controls. Similarly, 80% of SARS-CoV-1 survivors and 38.1% of NHIs had detectable spike-specific IFN-γ⁺ CD8⁺ T cells. SARS-CoV-1 survivors had significantly higher frequencies than controls, while NHIs and controls had comparable frequencies.

Finally, the authors assessed whether Ad5-nCoV vaccination would result in more robust and potent 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 measured by an ELISpot assay.

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, while approximately 60% of SARS-CoV-1 survivors had detectable IFN-γ⁺ CD8⁺ T cells.

Conclusions

Ad5-nCoV vaccination in SARS-CoV-1 survivors boosted nAbs against SARS-CoV-1 but had a lower magnitude and concentration of nAbs against SARS-CoV-2. Nonetheless, vaccination induced specific T-cell responses against SARS-CoV-2 variants in SARS-CoV-1 survivors and NHIs six months after vaccination, suggesting that vaccination is insufficient to increase the breadth and lifespan of increase SARS-CoV-2. specific antibody responses but results in a protracted T cell response.

Taken together, the study results suggest that SARS-CoV-1 survivors and NHIs have comparable post-vaccination T-cell and antibody responses against SARS-CoV-2.