Study: Covid-19 Vaccines — Immunity, variants, boosters. Image Credit: Dimitris Barletis/Shutterstock
Record
The unprecedented increase in morbidity and mortality associated with COVID-19 has led to the rapid development of SARS-CoV-2 vaccines worldwide. However, challenges regarding vaccinations against COVID-19 include uneven vaccination coverage, vaccine reluctance, waning immunity, and the emergence of SARS-CoV-2 variants of concern (VOCs) with increased immune evasion. This review summarized the SARS-CoV-2 pandemic scenario based on existing data and humoral and cell-mediated immune responses against SARS-CoV-2.
Antiviral immunity
Immune responses are generated due to innate or adaptive immunity. Innate immune responses are the first line of antiviral defense. They are rapidly activated upon recognition of pathogen-associated molecular patterns (PAMPs) by cellular PRRs (pattern recognition receptors) such as toll-like receptors (TLRs). Innate immunity includes cytokines such as type I IFNs (interferons) and cellular responses from macrophages and monocytes, neutrophils, natural killer (NK) cells, and dendritic cells. Adaptive humoral and cell-mediated immune responses by antibodies (Abs) and lymphocytes, respectively, constitute the next line of antiviral defense and include SARS-CoV-2 epitope recognition. B lymphocytes produce Abs that bind to the SARS-CoV-2 spike (S) protein and either neutralize or eliminate SARS-CoV-2. The complex of differentiation (CD)8+ T cells eliminate cells infected with SARS-CoV-2 while CD4+ T cells help CD8+ T cells. Neutralizing Abs (nAbs) essentially prevent the acquisition of COVID-19, while the combination of cell-mediated and humoral immune responses likely limits SARS-CoV-2 replication after infection and prevents severe outcomes of COVID-19, such as introductions to hospital and deaths.
SARS-CoV-2 variants and vaccines
In the spring of 2020, SARS-CoV-2 acquired mutations rapidly, including the D614G mutation in the spike (S) protein that conferred an immune fitness advantage to the virus. Subsequently, multiple SARS-CoV-2 VOCs emerged with greater transmissibility and immune evasion. In late 2020, Alpha, Beta and Gamma VOCs appeared, which were then replaced worldwide by Delta VOC and later by the highly contagious Omicron VOC. In addition, Omicron subvariants such as BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4, and BA.5 emerged, and nAb responses against BA.5 were reported to be threefold lower than those against BA .1 and BA.2. Several SARS-CoV-2 vaccines (n=10) have been approved for global use by the World Health Organization (WHO) and include vaccine platforms such as (i) inactivated SARS-CoV-2 vaccines Covilo (Sinopharm), CoronaVac (Sinovac), and Covaxin (Bharat Biotech) messenger ribonucleic acid (mRNA) vaccines; mRNA-1273 (Moderna) and BNT162b2 (Pfizer–BioNTech) adenovirus vector-based COVID-19 vaccines; [Vaxzevria and ChAdOx1 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson–Janssen)]and (iv) adjuvanted protein vaccines [NVX-CoV2373 and Nuvaxovid (Novavax)]. Adenovirus vector-based vaccines have shown lower efficacy but higher stability than mRNA vaccines and have been used extensively among developing countries, although serious cases of vaccine-induced immune thrombotic thrombocytopenia (VITT) have been reported following Ad26. Vaccination against COV2.S in the United States (US). VITT has also been reported in Europe with ChAdOx1 vaccination and in the USA with mRNA-1273 vaccination. Complications such as pericarditis and myocarditis have been reported after mRNA-1273 and BNT162b2 vaccinations in young men, although most cases were mild. Other regulatory agencies have approved additional vaccines for COVID-19. mRNA-1273 and BNT162b2 vaccines induce high nAb responses and protective efficacy. However, high initial serum nAb titers decline by three to six months and decline further by eight months. In contrast, Ad26.COV2.S elicits lower initial nAb titers, but nAb responses and clinical efficacy are quite durable for ≥8 months. At six to eight months, nAb responses are similar to BNT162b2, mRNA-1273, and Ad26.COV2.S vaccines. Attenuation of immune responses after mRNA vaccinations has been associated with relapsing SARS-CoV-2 infections among vaccinated individuals, and transmission of SARS-CoV-2 has been reported even in fully vaccinated individuals. Hybrid immunity as a result of natural infections and vaccinations has produced stronger immune protection than infection or vaccination alone. Cell-mediated immune responses have been elicited by adenovirus vector-based and mRNA-based COVID-19 vaccines and have been reported to be more durable than nAb serological titers. In immunocompromised individuals, both nAb and T cell responses to COVID-19 vaccines are lower, and additional doses of vaccine and prophylactic treatment with monoclonal Abs (mAbs) have been suggested for such individuals. Vaccination-induced primary nAb responses have shown limited cross-reactivity to Omicron, which increases post-booster vaccinations for COVID-19. However, boosted titers decline within four months of the booster (third) mRNA vaccination and four weeks (or more for severe cases) after the fourth mRNA vaccination. In contrast, cell-mediated immune responses have remained largely intact.
conclusion
Based on the findings, booster vaccinations are beneficial, but updated COVID-19 vaccines need to be developed for sustained immune protection against emerging SARS-CoV-2 VOCs, especially for immunocompromised individuals. The goal of SARS-CoV-2 vaccinations should be to provide long-term immunological protection against the severity effects of COVID-19. Hybrid immunity provides stronger immune protection than natural SARS-CoV-2 infections or vaccinations, and CD8 T cells alone contribute to immune protection when nAb titers are subprotective.
