The Impact of Immunosenescence on Humoral Immune Response Variation after Influenza A/H1N1 Vaccination in Older Subjects

Abstract

BackgroundAlthough influenza causes significant morbidity and mortality in the elderly, the factors underlying the reduced vaccine immunogenicity and efficacy in this age group are not completely understood. Age and immunosenescence factors, and their impact on humoral immunity after influenza vaccination, are of growing interest for the development of better vaccines for the elderly.MethodsWe assessed associations between age and immunosenescence markers (T cell receptor rearrangement excision circles – TREC content, peripheral white blood cell telomerase – TERT expression and CD28 expression on T cells) and influenza A/H1N1 vaccine-induced measures of humoral immunity in 106 older subjects at baseline and three timepoints post-vaccination.ResultsTERT activity (TERT mRNA expression) was significantly positively correlated with the observed increase in the influenza-specific memory B cell ELISPOT response at Day 28 compared to baseline (p-value=0.025). TREC levels were positively correlated with the baseline and early (Day 3) influenza A/H1N1-specific memory B cell ELISPOT response (p-value=0.042 and p-value=0.035, respectively). The expression and/or expression change of CD28 on CD4+ and/or CD8+ T cells at baseline and Day 3 was positively correlated with the influenza A/H1N1-specific memory B cell ELISPOT response at baseline, Day 28 and Day 75 post-vaccination. In a multivariable analysis, the peak antibody response (HAI and/or VNA at Day 28) was negatively associated with age, the percentage of CD8+CD28low T cells, IgD+CD27- naïve B cells, and percentage overall CD20- B cells and plasmablasts, measured at Day 3 post-vaccination. The early change in influenza-specific memory B cell ELISPOT response was positively correlated with the observed increase in influenza A/H1N1-specific HAI antibodies at Day 28 and Day 75 relative to baseline (p-value=0.007 and p-value=0.005, respectively).ConclusionOur data suggest that influenza-specific humoral immunity is significantly influenced by age, and that specific markers of immunosenescence (e.g., the baseline/early expression of CD28 on CD4+ and/or CD8+ T cells and T cell immune abnormalities) are correlated with different humoral immune response outcomes observed after vaccination in older individuals, and thus can be potentially used to predict vaccine immunogenicity.

Reevaluation of immune activation in the era of cART and an aging HIV-infected population

“…The prevalence of existing humoral immune responses in the human population complicates use of the influenza vaccination model for determining immunological predictors of vaccine responsiveness. Nevertheless, many groups have used and continue to use the seasonal flu vaccine to probe immune competence and explore new biomarkers in order to improve vaccine design (29,(37)(38)(39)(40)(41)(42)(43). The use herein of absolute response and response score criteria facilitates comparisons without altering the conventional definitions for determining vaccine responder status.…”

Restoration of Thymus Function with Bioengineered Thymus Organoids

“…It is projected that by the year 2030, more than 20% of U.S. population will be aged 65 or older. Aging is associated with progressive deterioration of immune function that leads to increased susceptibility to opportunistic infections, decreased responsiveness to vaccines, and increased incidence of autoimmunity and cancer [105, 106]. How to prevent/reverse immunosenescence in aged individuals to ensure a healthy, quality life and to cut down societal health care-related cost remains a major challenge to medical research [107, 108].…”

The composition of immune cells serves as a predictor of adaptive immunity in a cohort of 50‐ to 74‐year‐old adults

“…13,14,16 A cell-based microneutralization assay was performed with influenza A/H1N1 virus stimulation (200 plaqueforming units per 5 µl), as described previously, 6,13 to determine influenza A/H1N1-specific neutralizing antibody titres from subject sera at each time-point pre-and post-vaccination.…”

“…The information needed to explain and predict the level of protection that individuals will receive from the influenza vaccine is lacking. [4][5][6] Abbreviations: APC, antigen-presenting cell; DC, dendritic cell; HAI, haemagglutination inhibition; IL, interleukin; mDC, myeloid dendritic cell; NK, natural killer cell; PBMC, peripheral blood mononuclear cell; pDC, plasmacytoid dendritic cell; Treg, regulatory T cell; VNA, virus neutralizing antibody Leucocyte populations as predictors of response to influenza vaccination Recombination events between various influenza strains (antigenic shift) result in more dramatic changes in viral antigenicity and can lead to influenza pandemics, which have far greater public health consequences. Examples of these include the H1N1 'Spanish Flu' in 1918, the H2N2 'Asian Flu' in 1957, the H3N2 'Hong Kong Flu' in 1968, the H5N1 'Bird Flu' in 2004, as well as the more recent H1N1 'Swine Flu' pandemic in 2009.…”