A Review on Immunological Responses to SARS-CoV-2 and Various COVID-19 Vaccine Regimens

Abstract

The transmission of SARS-CoV-2 has caused serious health crises globally. So far, 7 vaccines that are already being assessed in Phase IV clinical trials are, Comirnaty/ Pfizer; Spikevax/Moderna (m RNA vaccine); Vaxzevria or Covishield; Ad26.COV2.S; Ad5-nCoV (adenoviral vector-based vaccine); CoronaVac and BBIBP-CorV (inactivated virus vaccine). Besides, there are about 280 vaccines that are undergoing preclinical and clinical trials including Sputnik-V, Covaxin or BBV152, and NVX-CoV2373. These vaccines are being studied for their immunological responses and efficiency against COVID-19, and have been reported to demonstrate effective T and B cell responses. However, the long-lasting immunity of these vaccine regimens still needs to be investigated. An in-depth understanding of the vaccine efficacy and immune control mechanism is imperative for the rational purposing and implementation of the vaccines. Hence, in this review, we have comprehensively discussed the immune response induced in COVID-19 patients, as well as in the convalescent individuals to avoid reinfection. Moreover, we have also summarized the immunological responses and prophylactic efficacy of various COVID-19 vaccine regimens. In this context, this review can give insights into the development of effective vaccines against SARS-CoV-2 and its variants in the future.

Keywords: COVID-19; clinical trial; convalescent individuals; immune response; vaccine regimens.

Fig. 1

Immune responses and protection against SARS-CoV-2: (i, ii, iii) SARS-CoV-2 binds to the ACE-2 receptor and gets internalized via endocytosis with the help of TMPRSS2. (iv) Inside the host cell Viral RNA is recognized by TLR3 and some sensors of viral infection (MDA 5 and RIG- I), (v) which induce production of IFN-I, and (vi) activation of various cellular responses (ROS production, calcium influx), (vii) leading to the production and activation of NLRp3 inflammasome, which further activates caspases that cleaves pro-IL-1β, pro-IL-18, and gasdermin D, leading to their activation (IL-1β, IL-18, and gasdermin D). (viii, ix) Macrophages also produce cytokines that activate enough amount of NK cells, (x, xi) leading to the production of IFNγ, IL-2, and granzyme B, which causes pyroptosis of the infected cell. (xii) However, the viral RNA can also use the host machinery to form new virions, (xiii) which can be recognized by the APCs leading to their presentation to the T cells, which activates Th and Tc cells. (xiv) Th cells produce IFNγ, IL-2, and TNF α, (xv, xvi) which activate the B cells to produce spike-specific and neutralizing antibodies resulting in the virus clearance. (xvii) The cytokines produced from Th cells also induce the Tc cells to produce perforins, (xviii) which leads to pyroptosis of the infected cell and protection against the disease.

Fig. 2

SARS-CoV-2 Vaccines in development: Adenoviral vector vaccine (Vaxzevria, Ad5-nCov, and Ad26.COV2.S) - The adenovirus is designed to contain information encoding the wild type spike protein. As this modified adenovirus DNA enters the host cell, it uses the host machinery to translate the viral antigens which are presented to the T cells, leading to the activation of both Th and Tc cells. The Th cells produce cytokines that activate the B cells and Tc cells. The B cells differentiate into plasma B cells and memory B cells. The plasma B cells produce spike-specific IgG and IgM antibodies along with the neutralizing antibodies that play a major role in virus clearance. The Tc cells produce perforins that are also involved in virus clearance. mRNA-based vaccines (Comirnaty, and Spikevax)- The vaccine consists of an mRNA encapsulated in a lipid nanoparticle and has the information required to synthesize a stable prefusion of the spike protein. This m RNA when inside the host cells uses its machinery to translate the viral antigens, which are presented to the T cells, and thus activate the adaptive immune response against the Spike protein. Inactivated virus vaccine (CoronaVac, Covaxin, and BBIBP-CorV) - The inactivated whole virus when inside the host cell are presented by the APCs to the T cells which activate the adaptive immune response. The role of innate immune response and memory B cells in virus clearance still needs to be investigated.

Fig. 3

Main adverse effects of various SARS-CoV-2 vaccine regimens. As illustrated, there have been rare cases of these severe side effects.