COVID-19 mRNA boosters induce strong but not durable immune responses in the elderly

Research published in journals The forefront of immunology A third booster dose of coronavirus disease 2019 (COVID-19) effectively induces an immune response against an immunologically more compatible variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) However, the booster immunity is temporary and will gradually decline over time.

study: Decrease in specific antibodies to Delta and Omicron variants 5 months after the third dose of BNT162b2 SARS-CoV-2 vaccine in the elderlyImage credit: Imagineer/Shutterstock

Background

A COVID-19 vaccine developed in response to the ongoing pandemic has shown great efficiency in controlling SARS-CoV-2 infection rates and associated mortality in the early stages of global vaccine deployment . However, with the emergence of immunologically more aggressive viral variants such as Delta and Omicron, a decline in vaccine efficacy has been observed worldwide.

The majority of COVID-19 vaccines consist of a two-dose regimen given at regular intervals. However, given the decline in vaccine efficacy, a third booster was introduced into the mass vaccination programme. Studies conducted in real-world setups show that the 3rd booster is highly effective against Delta and Omicron infections and related illness severity, hospitalizations, and mortality .

In current research, scientists believe that over the long term effectiveness of A third booster dose of mRNA-based COVID-19 vaccine (Pfizer/BioNTech) in the elderly.

research design

The survey was conducted on 36 people between the ages of 61 and 81. The participant received two doses of her Pfizer her vaccine 21 days apart. A third booster dose was given 189 to 270 days after the first dose.

Blood samples were taken from participants 2 and 5 months after primary vaccination and 1 and 4 months after booster vaccination.Samples were tested for SARS-CoV-2 spike-specific antibodies, memory B-cell responses, and T cells response.

Antibody responses induced by mRNA COVID-19 vaccine

Antibody levels analyzed 2 months after primary vaccination revealed a significant induction in response to wild-type SARS-CoV-2. However, a significant proportion of participants (25%) showed low antibody responses.

For virus variants, significantly lower antibodies at 2 months against tested variants (alpha, beta, gamma, kappa, delta, delta plus, and ommicron) compared to wild-type virus A response was observed. The response was the worst for the omicron variant.

Antibody responses to wild-type virus remained unchanged 5 months after primary vaccination. However, at this time point we observed a significant reduction in antibody responses to all tested variants. The proportion of low antibody responders increased from 25% to 71-81%, especially for variant-specific antibody responses.

A significant induction of antibody responses was observed against wild-type virus and mutants tested at 1 month after booster vaccination. Even low-responders showed similar induction. However, a significant decline in antibody responses was observed at 4 months compared to 1 month.

Despite the reduced efficacy of the vaccine, the antibody response observed 4 months after booster vaccination was significantly higher than 5 months after primary vaccination.

Memory B and T cell responses induced by mRNA COVID-19 vaccine

A significant induction of memory B cell responses was observed 1 month after booster vaccination and remained unchanged after 4 months. Responses 4 months after booster vaccination were higher than responses 5 months after primary vaccination.

Induction and reduction of memory B and T cell responses to Spike after booster vaccination. RBD-specific memory B (N=10), spike protein-specific CD8 (N=16), CD4 Th1 (N=16) or CD4 Th2 (N=13) responses. The frequency of IgG RBD-specific memory B cells among total IgG antibody-secreting cells (ASC) is presented for memory B cell responses. For CD8, CD4 Th1, and CD4 Th2 responses, data shown are spot-forming units (SFU) per million PBMC from paired samples at four time points. Each data point represents normalized average spot counts from duplicate wells after subtracting media-only controls. Friedman’s test and post-hoc test with Dunn’s multiple comparison test were used to compare between time points. *, P-value <0.05; **. P-value <0.01; ***, P-value <0.001.

Regarding cell-mediated immune responses, robust and sustained T-cell responses were observed after 5 months compared to 2 months after primary vaccination.

One month after booster vaccination, a significant induction of CD4 type 1 helper cell responses was observed. After booster vaccination, only his 12% and 6% of participants developed CD8 and CD4 type 1 helper cell responses, respectively.

Overall T cell responses remained unchanged 4 months after booster vaccination. However, approximately 50%, 43%, and 84% of participants had reduced CD8 type 1 T helper cell, CD4 type 1 T helper cell, and CD4 type 2 T helper cell responses, respectively. Furthermore, 4 months after booster vaccination, approximately 25%, 18%, and 53% of participants had CD8 type 1 T helper cell, CD4 type 1 T helper cell, and CD4 type 2 T helper cell responses. decreased respectively. Up to 5 months after the first vaccination.

Significance of research

This study reveals that a third booster dose of mRNA COVID-19 vaccine can induce a strong but transient immune response in the elderly. However, the rapid decline in effectiveness of booster vaccinations highlights the need for an additional her fourth dose to protect the elderly from severe her COVID-19. increase.