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Long-term immune response induced by mRNA vaccines

Attaining herd immunity, whether by infection or by vaccination, is necessary to control the pandemic while SARS-CoV-2 continues to circulate. Different vaccines have been available for several months now, notably the mRNA vaccines. These vaccines encode the spike surface protein of the original Wuhan strain and have been widely administered throughout the world. They are extremely effective in protecting against symptomatic forms of COVID-19.

Immunologically, these vaccines elicit a significant antibody response that correlates with protection against the virus. These antibodies circulate in the body for at least 6 months, but their level reduces with time. Vaccination also triggers B and T lymphocyte responses that are important for immune memory. Studies have taken place, but they have concentrated on immune memory after an infection, or short term immunity following vaccination. Now researchers at the University of Pennsylvania (USA) have analysed the immune response several months after mRNA vaccination and the response induced against new variants.

The researchers studied a cohort of 61 individuals who had been given an mRNA vaccine (Pfizer-BioNTech or Moderna). These 61 individuals formed 2 groups, according to whether they had been infected by SARS-CoV-2 prior to infection (16 individuals) or not (45 individuals). 6 blood samples were taken from each individual, before vaccination and up to 6 months after their 2nd dose.

The scientists measured antibodies and B and T cells specifically targeting SARS-CoV-2. They firstly confirmed that the mRNA vaccines provoke a strong antibody response, which peaks one week after the 2nd injection and then diminishes progressively. Weakening of immunity was similar in people who had been infected by SARS-CoV-2 previously and those who had not. Despite the reduction in levels of antibodies, which slows between 3 and 6 months after the 2nd dose, they remained detectable after 6 months.

The scientists then looked at B memory cells circulating in the blood. These could be detected in all vaccinated, non-infected individuals after the 2nd dose. Levels of B cells even rose between 3 and 6 months after vaccination. Individuals having been infected by the virus already had a strong population of B-memory cells before vaccination, and numbers were reinforced after the 1st dose. However, after the second dose, levels hardly changed. 6 months after vaccination, infected and non-infected individuals had similar levels of B-memory cells, which seem to be effective against variants. The vaccine also induced CD4 T (helper) and CD8 (cytotoxic) memory cells in all vaccinated individuals, whether they had been infected by the virus or not. An early CD4 T cell response appears to be a marker of a strong antibody response in the 3-6 months after vaccination.

In conclusion, this study shows that anti-COVID-19 mRNA vaccines generate a strong immune response for up to 6 months after vaccination. This response involves high quality B cells and a strong T cell response in the majority of individuals. The response seems relatively effective against variants. However, since some developed countries now recommend a 3rd dose of the vaccine, it is essential to have a good understanding of immune memory in the long-term. In addition, since these vaccines were based on the original strain, the emergence of variants may diminish their efficacy. This study was limited to young individuals in good health. It is now necessary to analyse long term immunity induced by vaccination in elderly or chronically ill people. 

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