SARS-CoV-2 Neutralization Impairment After Booster Vaccination in Older Adults

A recent study published in medRxiv* A preprint server explores the magnitude and potential molecular basis of the reduced vaccine response observed in older adults who received a booster vaccine for novel coronavirus disease (COVID-19).

study: Impaired atypical B-cell and SARS-CoV-2 neutralization after booster vaccination in the elderlyImage Credit: Olena Yakobchuk / Shutterstock.com

Background

Immunological memory, defined as the ability of the immune system to respond more strongly after re-exposure to the same pathogen, is a fundamental operating principle of vaccination. Immunization remains the most effective strategy to prevent the spread of infectious agents. This is evidenced by its success in preventing various diseases caused by viruses such as polio and, more recently, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Long-term vaccine immunity is essential for protection against rapidly emerging SARS-CoV-2 variants. effectiveness of This form of immunity helps the host circulate, bind, and Neutralizing antibody Spike-specific T-cell and B-cell responses.

Immunization is very important because many older people have comorbidities and weakened immune systems. Nevertheless, despite vaccination, age remains the main risk factor for COVID-19-related hospitalization and death.

This is because older people have a suboptimal response to the first vaccination. However, the effect of aging on her COVID-19 booster dose response remains unexplored.

Current evidence suggests that age has a profound effect on the immune response induced by the messenger ribonucleic acid (mRNA) COVID-19 vaccine, especially after the first dose of the vaccine. This difference appeared to decrease with the second booster dose. However, despite a second dose of vaccination, her T-cell responses remain poor in the elderly.

Older people remain disproportionately vulnerable to worsening health conditions after SARS-CoV-2 infection, and thus remain an important target demographic for enhancing immunization responses.

About research

The aim of the current study was to determine the effect of age on the response to a third dose of the COVID-19 vaccine and to determine the mechanistic basis of the various age-induced immune responses. The study focused on people who received two doses of the Covishield-Astrazeneca AZD1222 vaccine and one dose of the mRNA booster.

Blood samples were taken one month and six months after the second dose and one month after the third booster dose. The median age of the participants was 67, and none were older than 75.

This study evaluated the magnitude and persistence of neutralizing antibody and T-cell responses generated by Covishield after the first two doses in 36 participants. Multiparameter flow cytometry and single-cell RNA sequencing were applied to peripheral blood mononuclear cells (PBMCs) obtained 1 month after the second dose of Covishield vaccine and 1 month after mRNA booster administration.cellular phenotype, single-cell transcriptome, and antigen Receptor sequences were compared longitudinally across age groups.

Because the complementarity determining region 3 (CDR3) plays a key role in antigen binding and specificity, the antigen-binding capacity of memory B cells in single-cell B-cell receptor sequencing (scBCRseq) data is a function of their CDR3 sequences. determined by analysis. The public COVID-19 antibody database (Cov-Abdab) was used as it contains 10,000 ly validated CDR3 sequences for SARS-CoV-2 specific antibodies.

Survey results

Neutralizing antibody titers among different age groups at 1 and 6 months after second vaccination of three SARS-CoV-2 strains, including wild-type (WT), Delta, and Omicron variants There was no change in As expected, neutralizing antibody titers decreased by 1 log from 1 to 6 months after booster administration.

Neutralizing antibody measurements indicated that the mRNA booster elicited a strong response. However, participants over the age of 70 showed lower responses. When tested for BCR-enriched motifs post-vaccination compared to control infected naive B cells, atypical B cells have memory cells expressing BCRs consistent with SARS-CoV-2 antibodies in individuals over 70 years of age. cells were present in large proportions. This effect was more pronounced after mRNA booster administration.

Longitudinal neutralizing plasma antibody titers against Wu-1 D614G WT, Delta, and Omicron BA.1 variants from AZD1222 vaccinees boosted with mRNA-based vaccines. (A) Study design – 36 individuals vaccinated with AZD1222 and boosted with an mRNA-based vaccine were recruited. Longitudinal bleeds were performed 1 month after the second dose, 6 months after the second dose, and 1 month after the boost. (B) Total anti-spike IgG binding antibody responses 1 month after the second dose, 6 months after the second dose, and 1 month after the booster. The Wilcoxon matched-pairs signed-rank test was used. ****p < 0.0001. (C) Total anti-spike IgG binding antibody responses at 1 month post-second dose, 6 months post-second dose, and 1 month post-booster stratified by <70 and >70 years. Mann-Whitney test was used. NS is not important. (D) Serum neutralization titers (ID50) were measured against Wu-1D614GWT, Delta, and Omicron at each time point. The Wilcoxon matched pair signed-rank test was used to determine the significance of titers between time points. **p < 0.01, ***p < 0.001, ****p < 0.0001. (E) Neutralizing titers (ID50) against Wu-1 D614G WT, Delta, and Omicron BA.1 stratified by <70 and >70 years. Mann-Whitney test was used. NS is not important. *p < 0.05, **p < 0.01.

People aged 70 years and older showed decreased B-cell activation after the second (Covishield) vaccination. Transcriptional modifications in B cells were more robust and/or long lasting.

Percentages of receptor-binding domain (RBD) and spike-binding non-naïve (IgD) B cells were elevated 1 month after mRNA booster administration and comparable to lymphocytes at 1 and 6 months. was given. Dosage for the second vaccination (Covishield).

Older patients had a higher percentage of antigen-specific, atypical, non-naive B cells than younger patients, with an average of 39% IgD-RBD+ B cells in patients aged 70 years or older.

The mRNA booster dose stimulated proliferation of vaccine-specific memory B cells. However, senescence alters the differentiation of her B cells into atypical memory B cells. This reduced the efficiency of humoral immunity.

Covishield vaccine conferred long-lasting T-cell immunity, which increased after mRNA booster administration. However, the booster effect appeared to be attenuated in elderly patients, especially with respect to interleukin (IL)-2 responses.

Continued transcriptional activation of monocytes, plasmacytoid dendritic cells (pDC), and classical dendritic cells (cDC) was detected even 1 month after booster mRNA vaccination, leading to T and B cell activation .

Myeloid cells, unlike adaptive immune cells, lack conventional immune memory. Consequently, the increased myeloid cell activation after mRNA booster administration compared to after two Covishield administrations represents a vaccine-specific property.

Limitations

The current study identified several limitations, including small sample size, peripheral blood sampling to assess vaccine-induced immune responses, and lack of clinical data related to protection and severity of COVID-19. rice field. Such studies are becoming increasingly difficult due to the different time intervals between vaccinations.

Future research should focus on the mechanisms of immunocompromise in the elderly and the effects of fourth vaccination and aging..

*Important Notices

medrex sib We publish a non-peer-reviewed, preliminary scientific report and should not be taken as conclusive, to guide clinical practice/health-related actions, or to be treated as established information.