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

By Tarun Sai LomteReviewed by Benedette Cuffari, M.Sc.Oct 23 2022

In a recent Cell Reports jouirnal 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 response in SARS-CoV-1 survivors. Image Credit: creativeneko / Shutterstock.com

Background

SARS-CoV-1, the causal agent of the 2002 epidemic, is a beta-CoV from the Coronaviridae family. SARS-CoV-1 infection elicits humoral and cellular immune responses. Antibody responses may persist for two to three years post-infection, and specific memory B-cells (MBCs) decline to undetectable levels by 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 exhibit 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 common cold CoVs.

One study noted that more than 90% of healthy adults have immunoglobulin G (IgG) specific to all human common cold CoVs. However, whether coronavirus disease 2019 (COVID-19) vaccines boost pre-existing cross-reactive memory T-cell responses remain elusive.

Study findings

In the present study, researchers analyze SARS-CoV-2-specific antibody and T-cell responses after one 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. Additionally, three vaccinated survivors were included in the study approximately six months after vaccination.

Further, 18 naïve healthy individuals (NHIs) who received the Ad5-nCoV vaccine were also enrolled in the current study. Ten cryopreserved specimens of peripheral blood mononuclear cells (PBMCs) and serum collected from healthy donors before September 2019 served as controls.

The 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 against SARS-CoV-1, none had nAbs against SARS-CoV-2 before vaccination. After vaccination, 13 of these 23 survivors neutralized SARS-CoV-2 WA1; however, neutralization against Omicron sub-variants BA.1, BA.2, BA.2.12.1, and BA.4/5 was attenuated. Nonetheless, nAb geometric mean titers (GMTs) were higher against SARS-CoV-1 than WA1.

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

Because the antibody responses between vaccinated SARS survivors and NHIs were comparable, the researchers investigated if the same applied to 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 (ELISpot) assays.

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

All survivors and 16 NHIs had detectable levels of IFN-γ-secreting spike-specific T-cells. SARS-CoV-2 spike-specific AIM⁺ cluster of differentiation 4-positive (CD4⁺) T-cells were detected in 17 SARS survivors and 16 NHIs, with comparable median 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 revealed 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 median 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.

Lastly, the authors assessed if 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, whereas 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 lower magnitude and levels of nAbs against SARS-CoV-2. Nonetheless, vaccination in SARS-CoV-1 survivors and NHIs induced specific T-cell responses against SARS-CoV-2 variants six months post-vaccination, thus suggesting that vaccination is inadequate to enhance the breadth and life of SARS-CoV-2-specific antibody responses but leads to protracted T-cell response.

Taken together, the study findings indicated that SARS-CoV-1 survivors and NHIs have comparable T-cell and antibody responses against SARS-CoV-2 after vaccination.