Cellular and Humoral Immune Responses in Covid-19 and Immunotherapeutic Approaches

Abstract

Coronavirus disease 2019 (Covid-19), caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), can range in severity from asymptomatic to severe/critical disease. SARS-CoV-2 uses angiotensin-converting enzyme 2 to infect cells leading to a strong inflammatory response, which is most profound in patients who progress to severe Covid-19. Recent studies have begun to unravel some of the differences in the innate and adaptive immune response to SARS-CoV-2 in patients with different degrees of disease severity. These studies have attributed the severe form of Covid-19 to a dysfunctional innate immune response, such as a delayed and/or deficient type I interferon response, coupled with an exaggerated and/or a dysfunctional adaptive immunity. Differences in T-cell (including CD4 + T-cells, CD8 + T-cells, T follicular helper cells, γδ-T-cells, and regulatory T-cells) and B-cell (transitional cells, double-negative 2 cells, antibody-secreting cells) responses have been identified in patients with severe disease compared to mild cases. Moreover, differences in the kinetic/titer of neutralizing antibody responses have been described in severe disease, which may be confounded by antibody-dependent enhancement. Importantly, the presence of preexisting autoantibodies against type I interferon has been described as a major cause of severe/critical disease. Additionally, priorVaccine and multiple vaccine exposure, trained innate immunity, cross-reactive immunity, and serological immune imprinting may all contribute towards disease severity and outcome. Several therapeutic and preventative approaches have been under intense investigations; these include vaccines (three of which have passed Phase 3 clinical trials), therapeutic antibodies, and immunosuppressants.

High individual heterogeneity of neutralizing activities against the original 4 strain and 9 different variants of SARS-CoV-2

“…Despite the promising viral neutralization profiles of vaccinated individuals with the Pfizer/BioNTech vaccines in our cohort, a recent sero-epidemiological study showed that reinfection among patients previously infected by SARS-CoV-2 occurs at a lower rate (0.23%) than infection occurrence within previously vaccinated patients (5.1%) [38]. These findings are inconsistent with the outcomes obtained by the seroneutralization tests, but viral neutralization tests consist of in vitro approaches that may not reflect the effect of cellular immunity within the human body [39,40], as this technique is based exclusively on antibody-antigen interactions. A study published in May 2020 reported that during a COVID-19 infection, the SARS-CoV-2 spike (S) protein was found to be a nondominant target of the human CD8+ T cell response and that the recognition of the SARS-CoV-2 M (Matrix) antigen was similarly strong to the S antigen, which is unlike other coronaviruses [41].…”

High individual heterogeneity of neutralizing activities against the original strain and 9 different variants of SARS-CoV-2

“…Despite the promising viral neutralization pro les of vaccinated individuals with the P zer/BioNTech vaccines in our cohort, a recent sero-epidemiological study showed that reinfection among patients previously infected by SARS-CoV-2 occurs at a lower rate (0.23%) than infection occurrence within previously vaccinated patients (5.1%) [38]. These ndings are inconsistent with the outcomes obtained by the seroneutralization tests, but viral neutralization tests consist of in vitro approaches that may not re ect the effect of cellular immunity within the human body [39,40], as this technique is based exclusively on antibody-antigen interactions. A study published in May 2020 reported that during a COVID-19 infection, the SARS-CoV-2 spike (S) protein was found to be a nondominant target of the human CD8+ T cell response and that the recognition of the SARS-CoV-2 M (Matrix) antigen was similarly strong to the S antigen, which is unlike other coronaviruses [41].…”

PRAK-03202: A triple antigen virus-like particle vaccine candidate against SARS CoV-2

“…As of June 2021, with more than ∼3,840,223 deaths in total and 408,990 new cases each day, it is considered a serious threat to global public health. Although several vaccine candidates have initiated clinical testing, very little is currently known about their long-term humoral response ( Hasan et al, 2021 ). There are also currently no effective therapeutics ( Ho et al, 2004 ), calling for the urgent development of safe and effective therapeutics against COVID-19.…”