Which immune response could cause a vaccine against COVID-19?

Immune reactions caused by vaccination can help protect the organism, or sometimes may aggravate the condition. It is especially important now when multiple vaccines against COVID-19 are being developed. The top immunologists analyse types of immune response to predict what kind of vaccine would be the best.

The COVID-19 pandemic is still ongoing, and it is a major challenge for healthcare professionals worldwide. Currently, there are several strategies of preventing the spread of the disease caused by the SARS-CoV-2 virus, including confinement or quarantine measures, social distancing, use of face masks, and good hygiene - with frequent hand washing and application of antiseptics. However, it is clear that such restrictions affect our personal and professional lives. This is why vaccines against SARS-CoV-2 are being developed across the globe, as vaccination could help stop the pandemic. But these vaccines can be designed in a number of ways, and immune responses may be different. The recent keynote paper by Sechenov University scientists and their Swiss colleagues analyses which type of immune reaction would be more favourable so the vaccine could be effective. The study has been published in International Archives of Allergy and Immunology.

The vaccine, as expected, should efficiently induce high-affinity neutralising antibodies which would target SARS-CoV-2. At the same time, there are concerns that infection after vaccination might lead to eosinophilic lung disease and eosinophil associated Th2 immunopotentiation. Eosinophils are white blood cells involved in conditions such as bronchial asthma, eosinophilic oesophagitis, and hypereosinophilic syndromes. Currently, despite the limited available data, there is no indication that eosinophils play a protective or pathogenic role in COVID-19 infection.

However, eosinophils might still get involved when a person is vaccinated. For example, the research on potential vaccines against SARS-CoV-1, a closely related virus which caused an epidemic in 2002-2004, showed that pulmonary eosinophilia was induced in ferrets, monkeys, and mice after viral challenge. This fact suggests that vaccines against SARS-CoV-2 could also cause a similar immunopathology. Another source of complications might be the induced antibodies that promote viral uptake via Fc receptors.

According to the authors of the study, the most advantageous strategy should focus on vaccines that would induce the production of high-affinity virus-neutralising antibodies. These antibodies should block the interaction of SARS-CoV-2 with its cellular receptor - angiotensin-converting enzyme 2 (ACE2). Successful vaccines are expected to polarise the T-cell response towards type 1 immunity and prevent the stimulation of cytokines which induce T-helper 2 immunity.

"From our experience with the SARS-1 vaccine, we know that mice which received the whole spike protein (responsible for ACE2 binding) exhibited some eosinophilic complications due to the Th-2 polarisation of the immune response," says Alexander Karaulov, Head of the Department of Clinical Immunology and Allergology at Sechenov University and one of the authors of the paper. "At the same time, if the injected vaccine contained not the whole spike protein, but rather its receptor-binding domain which is directly involved in interactions with ACE2, immune-mediated pathologies (hypereosinophilic syndrome) could be avoided because of the high immunogenicity and high antibody titre. I believe this to be an important aspect, which remains poorly investigated."