Quantity, not quality, of antibody response decreased in the elderly

Blomberg, Bonnie B.; Frasca, Daniela

doi:10.1172/jci58406

Cited by 34 publications

(27 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, age-related immune senescence includes a loss of AID expression in B cells due to impairment of the transcription factor E47 (11). Furthermore, the drop in AID expression in the elderly (Ն60 years old) was shown to correlate with lower responses to annual vaccination with seasonal influenza virus vaccines (3,10). Our findings of high-affinity antibodies against H1N1pdm09 HA1 in the elderly strongly suggest that these antibodies are the product of long-term memory B cells or long-lived plasma cells that have undergone somatic hypermutation during early exposure to H1N1 viruses that circulated in the United States until 1957-1958 (1,2,9,21,33,39).…”

Section: Discussionmentioning

confidence: 99%

Influenza Virus H1N1pdm09 Infections in the Young and Old: Evidence of Greater Antibody Diversity and Affinity for the Hemagglutinin Globular Head Domain (HA1 Domain) in the Elderly than in Young Adults and Children

Verma

Dimitrova

Carter

et al. 2012

J Virol

View full text Add to dashboard Cite

The H1N1 2009 influenza virus (H1N1pdm09) pandemic had several unexpected features, including low morbidity and mortality in older populations. We performed in-depth evaluation of antibody responses generated following H1N1pdm09 infection of naïve ferrets and of 130 humans ranging from the very young (0 to 9 years old) to the very old (70 to 89 years old). In addition to hemagglutination inhibition (HI) titers, we used H1N1pdm09 whole-genome-fragment phage display libraries (GFPDL) to evaluate the antibody repertoires against internal genes, hemagglutinin (HA), and neuraminidase (NA) and also measured antibody affinity for antigenic domains within HA. GFPDL analyses of H1N1pdm09-infected ferrets demonstrated gradual development of antibody repertoires with a focus on M1 and HA1 by day 21 postinfection. In humans, H1N1pdm09 infection in the elderly (>70 years old) induced antibodies with broader epitope recognition in both the internal genes and the HA1 receptor binding domain (RBD) than for the younger age groups (0 to 69 years). Importantly, post-H1N1 infection serum antibodies from the elderly demonstrated substantially higher avidity for recombinant HA1 (rHA1) (but not HA2) than those from younger subjects (50% versus <22% 7 M urea resistance, respectively) and lower antibody dissociation rates using surface plasmon resonance. This is the first study in humans that provides evidence for a qualitatively superior antibody response in the elderly following H1N1pdm09 infection, indicative of recall of long-term memory B cells or long-lived plasma cells. These findings may help explain the age-related morbidity and mortality pattern observed during the H1N1pdm09 pandemic.

show abstract

Section: Discussionmentioning

confidence: 99%

Influenza Virus H1N1pdm09 Infections in the Young and Old: Evidence of Greater Antibody Diversity and Affinity for the Hemagglutinin Globular Head Domain (HA1 Domain) in the Elderly than in Young Adults and Children

Verma

Dimitrova

Carter

et al. 2012

J Virol

View full text Add to dashboard Cite

show abstract

“…The frequency of vaccine-specific plasmablasts and the concentration of plasmablast-derived polyclonal antibodies were lower in elderly than in young individuals, whereas the yields of secreted IgG per plasmablast and the vaccine-specific IgG avidity were similar [28]. Reduced T cell functions, age-related B cell defects and a diminished class switch recombination of antibody isotypes resulting in lower antibody responses characterize the impaired humoral and cellular immune response to influenza vaccination in elderly persons [29]. A recent report demonstrated that preexisting CD4+, but not CD8+, T cells respond to influenza internal proteins, which was associated with lower virus shedding and less severe illness [30].…”

Section: Response To Vaccinations In Neonates and In The Aged Populationmentioning

confidence: 99%

Differential Approaches for Vaccination from Childhood to Old Age

Prelog¹

2012

Gerontology

View full text Add to dashboard Cite

Primary prevention strategies, such as vaccinations at the age extremes, in neonates and elderly individuals, demonstrate a challenge to health professionals and public health specialists. The aspects of the differentiation and maturation of the adaptive immune system, the functional implications of immunological immaturity or immunosenescence and its impact on vaccine immunogenicity and efficacy will be highlighted in this review. Several approaches have been undertaken to promote Th1 responses in neonates and to enhance immune functions in elderly, such as conjugation to carrier proteins, addition of adjuvants, concomitant vaccination with other vaccines, change in antigen concentrations or dose intervals or use of different administration routes. Also, early protection by maternal vaccination seems to be beneficial in neonates. However, it also appears necessary to think of other end points than antibody concentrations to assess vaccine efficacy in neonates or elderly, as also the cellular immune response may be impaired by the mechanisms of immaturity, underlying health conditions, immunosuppressive treatments or immunosenescence. Thus, lifespan vaccine programs should be implemented to all individuals on a population level not only to improve herd protection and to maintain protective antibody levels and immune memory, but also to cover all age groups, to protect unvaccinated elderly persons and to provide indirect protection for neonates and small infants.

show abstract

“…The elderly (defined as people over 65 years of age) have higher rates of mortality related to influenza infection than adults or children (2)(3)(4)(5). Influenza vaccination elicits antibody responses in the elderly that are often compromised and wane before the next season, leading to poor protection in this highrisk population (6). Annual influenza vaccination is recommended for these high risk groups but is most effective in children and young adults (7,8).…”

Section: Introductionmentioning

confidence: 99%