Researchers from Mayo Clinic, United States of America, have reviewed the immunity developed against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19 disease. With the virus now infecting over 38 million people and claiming over a million lives worldwide, the race to develop an effective vaccine is on. Several questions are raised regarding the possible efficacy of a vaccine against this virus, and a variety of vaccines are being developed against the infection by several pharmaceutical companies.
Their review titled, “SARS-CoV-2 immunity: review and applications to phase 3 vaccine candidates,” is published in the prestigious journal The Lancet.
Need to learn about the immune response to SARS CoV-2
The first case of SARS-CoV-2 infection was reported in December 2019 in Wuhan, China. Since then, the infection and its disease process have been intensively studied, with many scientific studies focusing on the immune response to infection in the human body. The virus is highly infectious and spreads rapidly from one individual to another.
Coronaviruses, reinfections, and vaccines
Over the last two decades, there have been three novel coronaviruses that have been found to infect humans. These are the SARS CoV-1 (severe acute respiratory syndrome coronavirus 1), MERS (Middle East respiratory syndrome coronavirus), and SARS CoV-2.
Further, there are four seasonal human coronaviruses - 229E, NL63, OC43, and HKU1 that can result in community-acquired upper respiratory tract infections in one-third of the general population. These coronaviruses are both betacoronaviruses and alphacoronaviruses (229E and NL63) and belong to the Nidovirales order. Their genetic material is RNA.
Immunity against the seasonal coronaviruses lasts for around 80 days to a few years. Reinfections can be seen with 229E, NL63, and OC43. Rare cases of reinfections have been reported with SARS-CoV-2. Immunity against SARS CoV-1 and MERS has been seen for up to 2 to 3 years.
The team writes, “Understanding the mechanisms for short-duration immunity after a live viral infection is important because these processes might have considerable implications for the protection and durability of immunity induced by vaccines.”
Post-infection immunity to SARS-CoV-2
After an infection, two arms of the immune system are triggered – the B-cell and T-cell responses. A severe infection could result from the activation of CD4+ and CD8+ T cells, the team writes.
- Humoral immunity to SARS-CoV-2 – Here, the immune reaction is directed against viral surface glycoproteins. The virus contains spike glycoprotein and the nucleocapsid protein, against which the antibodies are developed. The authors wrote that these antibodies could neutralize viral infection of human cells and tissues containing angiotensin-converting enzyme 2 (ACE2). “Most patients with COVID-19 or those who are convalescent have virus-specific IgM, IgA, and IgG responses in the days after infection, suggesting that antibodies mediate protective immunity to SARS-CoV-2.”
- Cellular immunity to SARS-CoV-2 – Researchers found that levels of CD38+, HLA-DR+ T cells (both CD4+ and CD8+) increase during the first 7–10 days of COVID-19 symptoms and begins to return to baseline around day 20. Those with the severe illness have a more significant reduction in CD4+, and CD8+ T cell counts.
Vaccines in the pipeline
A vaccine is supposed to prevent a new infection with SARS CoV-2 in susceptible individuals. The vaccine would elicit protective immune responses that would prevent the infection or mitigate the morbidity and mortality caused by SARS-CoV-2 infection.
At present, it is known that a balanced humoral and Th1 (Helper T cells) directed cellular immune response is needed to protect an individual against COVID-19.
Some of the vaccines being developed include those which as “nucleic acid vaccines, inactivated virus vaccines, live attenuated vaccines, protein or peptide subunit vaccines, and viral-vectored vaccines,” write the researchers. Most of these are to be administered by the intramuscular route, and thus the immune system in the blood is to be activated rather than on mucosal surfaces.
Some of these are:
- Vaccines that are at Phase 1 trials:
- Vaccines that are at Phase 1 and 2 trials:
- Vaccines that are at Phase 3 trials:
Vaccine mediated infection
Each of the vaccines is supposed to trigger an antibody response. Authors write that there have been reported cases of antibody-dependent enhancement induced by vaccines when inactivated viruses are used in vaccines. There was evidence of vaccine-enhanced disease after the SARS-CoV-1 vaccine earlier, they wrote.
Conclusions and implications
The authors write that the virus and the immune response caused by it are still not well understood. They write, “multiple vaccine types will probably be needed across different populations (e.g., immune-immature infants, children, pregnant women, immunocompromised individuals, and immunosenescent individuals aged ≥65 years)”. Several clinical trials are also being conducted to see if other vaccines such as those against measles, mumps, and rubella vaccine and the Bacillus Calmette–Guérin vaccine (BCG vaccine) could protect COVID-19.
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