Innate immune system: For scientists, this is the key to perfecting COVID vaccines

Scientists are studying the multitude of factors that help determine the effectiveness of vaccines at the individual level (Getty)

Over the past two decades, the world has experienced a considerable number of disease outbreaks due to viral infections, such as yellow fever, dengue fever, Ebola, Zika, severe acute respiratory syndrome (SARS), respiratory syndrome from the Middle East and the new acute respiratory syndrome SARS-CoV-2. This pandemic has highlighted how disruptive sustained outbreaks of infectious diseases can be in society. Given the unpredictability of the emergence of the next pandemic, building capacity to respond quickly to any infectious disease threat is a global priority.

In what might be one of modern medicine’s most impressive achievements, several effective SARS-CoV-2 vaccines were developed in less than 12 months after the initial outbreak.. As of February 2022, ten vaccines against coronavirus disease 2019 (COVID-19) are approved for full or emergency use authorization by the World Health Organization. These approved vaccines span four distinct vaccine platforms, providing an additional layer of diversity in potential responses.

A group of scientists from Advanced Pathology Research Unit of the Department of Pathology and Medical Laboratory at Emory University in Atlanta, just published in the scientific journal Nature an in-depth discussion on how to understand heterogeneity in vaccine responses.

vaccines Moderna and Pfizer-BioNTech they use mRNA to produce antigens after vaccination. The vaccines of Johnson & Johnson and AstraZeneca different replication-incompetent adenoviral vectors are used to deliver the antigen. platforms Sinopharm and Sinovac-CoronaVac use β-propiolactone inactivated virus to promote immunogenicity. Platforms based on protein subunits are in advanced stages of development, one of which has been approved for emergency use authorization in Indonesia (Novax 8). Approved vaccines have efficacy rates of around 50% to 95%, with Moderna and Pfizer showing the highest short-term efficacy rates.

“Immunosuppressive drugs not only act directly on T cells and B cells, but also suppress the activity of innate immune cells,” the researchers explained.

Jeffrey Tomalka, a specialist at the University and first author of the research, explained that “although our understanding of the role of the microbiome and metabolome in modulating immune function and vaccine response has improved significantly in recent years , these discoveries they have not yet been translated into clinical settings to improve the modalities of vaccination. With a better understanding of the myriad of factors that help determine vaccine effectiveness at the individual level, one can begin to design strategies that mitigate heterogeneity in responses and improve vaccine effectiveness at the population level.”. Some of these are interesting and potentially easy solutions, others are less so and will require the combined ingenuity of the biomedical research community.

For specialists, there are at least two issues that could be prioritized in the development of vaccines: understand why elderly and/or immunocompromised people often react poorly to vaccines and unravel how environmental factors (including the microbiome and its metabolites) shape those responses.

There is substantial evidence that immunocompromised individuals show diminished responses to the SARS-CoV-2 vaccine. For example, people with conditions such as rheumatoid arthritis and systemic lupus erythematosus have lower seroconversion and antibody responses to vaccines. This is due, at least in part, to the effects of the use of immunosuppressive drugs.

Cancer patients are another group showing less effective vaccine responses to SARS-CoV-2. As with autoimmune diseases, reduced seroconversion rates and antibody responses are commonly associated with the use of cancer therapies.

People who are immunocompromised, due to pharmacological treatments for other illnesses, show reduced responses to the SARS-CoV-2 vaccine
People who are immunocompromised, due to pharmacological treatments for other illnesses, show reduced responses to the SARS-CoV-2 vaccine

Following this same theme, patients receiving organ transplants, who must take immunosuppressive drugs to prevent rejection, also have reduced antibody responses to SARS-CoV-2 vaccination.

Immunosuppressive drugs not only act directly on T cells and B cells, but also suppress the activity of innate immune cellswhich further dampens the induction of T and B lymphocyte responses -indicated the specialist-. The biggest challenge facing all of these vulnerable populations is that treatments that reduce efficacy are necessary for quality of life and, in many cases, survival. Simply removing people from these therapies is not a viable option.

Targeting the innate immune system as a way to improve the effectiveness of the SARS-CoV-2 vaccine is a promising avenue of research, the specialists concluded.. “Targeting conserved innate pathways upstream of adaptive immunity could prove to be an efficient and scalable way to generate improved vaccines,” Tomalka continued. To better define the complex impact of innate signaling on adaptive immunity and vaccine efficacy, well-informed controlled clinical studies of potential vaccine adjuvants are needed.

As stated in the document, this time provided “effective options the field can afford to slow down and begin the hard work of determining the comparison of host environmental factors, different adjuvants, and different vaccine platforms.””. Recent efforts to improve this kind of comparative vaccine research are advancing the field, but experts still say “we’re catching up.”

If we are ever to achieve the goal of a vaccine that protects an overwhelming majority of the human population against existing and yet to come variants, we need to get ahead of SARS-CoV-2 instead of chasing it.“said Tomalka.

Specialists agree that “if the factors discussed in this perspective and more particularly their impact on innate immunity are not taken into account when evaluating the effectiveness of vaccines, this could generate disparate results. in health care that could have a substantial impact on vulnerable and/or underserved populations”. .

Ensuring that effective vaccines are given to everyone, regardless of age, pre-existing conditions, biological sex, ethnicity or geographic location, is the only way to contain and potentially eliminate SARS- CoV-2. “Studying innate immunity within a holistic approach that incorporates all of the components that can affect vaccine responses is a pathway to developing a more universal and effective vaccine to help end this deadly pandemic. .concluded the researchers.

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