In a recent study published in Nature immunologyThe researchers summarized the observations of a humoral immune response induced in people infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).In addition, they discussed all types of SARS-CoV-2 infection and vaccine inducibility. Neutralizing antibody (NAbs). They also shared their views on nAb-inducing next-generation vaccine designs that broadly protect against multiple SARS-CoV-2 mutants (VOCs).
Review: Humoral response and antibodies against SARS-CoV-2 infection.. Image credit: NIAID
Humoral or antibody-mediated immune responses are an important component of adaptive immunity against viral infections, including coronavirus disease 2019 (COVID-19). This happens in two phases:
i) Extrafollicular (EF) phase, and
ii) Germinal center (GC) phase.
In the former EF phase, B cells that encounter the virus rapidly differentiate into plasma cells that produce nAb, which neutralizes SARS-CoV-2. These short-lived EF plasma cells have predominantly IgM isotypes, but can be switched with IgA or IgG. The latter GC phase takes weeks to begin, but usually lasts months. It produces antigen-specific (here SARS-CoV-2) B cells and, through affinity-based selection and somatic hypermutation, forms plasma cells with high affinity that remain localized in the bone marrow. In particular, both the EF and GC antibody responses produce memory B cells that remain present after removal of the primary infection.
Antibody types and antibody response to SARS-CoV-2 infection
SARS-CoV-2 infection stimulates the production of immunoglobulin (Ig) M, IgG, and IgA antibodies. They are at detectable levels in the patient’s serum within 1 week after onset of symptoms (PSO), including those that bind to SARS-CoV-2 spike (S) and nucleocapsid (N) proteins. In particular, these antibodies are of EF origin. The nAb titer for SARS-CoV-2 peaks at 3-4 weeks of PSO and then decays. However, IgG may be stable for several months compared to IgM and IgA antibodies.
The mucosal antibody, secretory IgA, is produced in the respiratory tract and plays an important role in preventing SARS-CoV-2 infection through the respiratory tract. It persists in the nasal fluid during several months of PSO and contributes to the development of resistance to reinfection.
Genome-level homology between other humans coronavirus (HCoVs) and SARS-CoV-2 are low but immunologically related. Cross-reactive memory B cells generated during a previous CoV infection may initiate a rapid EF antibody response, especially IgG and IgA, following a primary SARS-CoV-2 infection. Circulatory cross-reactive T cells in people who have not previously been exposed to SARS-CoV-2 also shape the clinical outcome of COVID-19.
SARS-CoV-2 infection increases circulation Autoantibodies Targets autoantigens, including cytokines, and chemokines such as interferon. In addition, SARS-CoV-2 infection causes autoimmune diseases (such as Guillain-Barré syndrome) with several antibodies.
The EF response causes nAb, which alone cannot control SARS-CoV-2 infection. Therefore, to prevent reinfection, the host relies on persistent nAb, memory B cells, and long-lived plasma cells with increased affinity maturation. All of these require a lively primary GC response. Unfortunately, it is difficult to directly assess a person’s GC response, except during autopsy of the deceased. In some cases, severe COVID-19 causes severe lymphocytopenia and is most likely to nullify the GC response. Also, a sustained GC response is the best correlation for a good prophylactic vaccine strategy.
Future outlook for COVID-19 vaccine
Most current SARS-CoV-2 vaccines target the prototype SARS-CoV-2 strain. However, with the emergence of antigenic escape VOCs such as Omicron, the world needs a widely neutralizing COVID-19 vaccine. Heterologous vaccine modality may help improve the neutralizing efficacy and breadth of COVID-19 boosters. However, future studies should also focus on the characteristics of B cells activated by booster immunity, epitope specificity, and the mechanism of action of booster-immunized antibodies.
Next-generation COVID-19 vaccines have the potential to target new VOC S-glycoproteins, similar to how influenza vaccines are renewed annually. However, it is also worth noting that the antibodies with the highest neutralizing power tend to have a limited width with respect to the spectrum of the mutant. The problem in designing a universal COVID-19 vaccine is to balance the efficacy and breadth of vaccination-induced nAb. Finally, researchers can consider approaches that combine multiple antigens from different VOCs into a single vaccine. For example, nanoparticle vaccines can use separate mosaic RBDs from different hCoV strains.
COVID-19 has become the most thoroughly studied viral disease in human history. An unprecedented global effort to understand how a host initiates an immune response to SARS-CoV-2 may help identify immunological correlations between infection and vaccine protection. I have. In addition, this facilitates the development of treatments for severe COVID-19.
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