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J Virol 2012 May;86(10):5515-22

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 N, Dimitrova M, Carter DM, Crevar CJ, Ross TM, Golding H, Khurana S

Abstract

The H1N1 2009 influenza (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 (0-9 year old) to the very old (70-89 year 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 to antigenic domains within HA. GFPDL analyses of H1N1pdm09 infected ferrets demonstrated gradual development of antibody repertoires with focusing on M1 and HA1 by day 21 post-infection. In humans, H1N1pdm09 infection in the elderly (> 70 years) induced antibodies with broader epitope recognition in both the internal genes and the HA1 receptor binding domain (RBD) compared with the younger age groups (0-69 years). Importantly, post-H1N1 infection serum antibodies from the elderly demonstrated substantially higher avidity to rHA1 (but not HA2) than from younger subjects (50% vs. <22% 7M urea resistance, respectively) and slower 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 or long-lived plasma cells. These findings may help explain the age-related morbidity and mortality pattern observed during the H1N1pdm09 pandemic.


Category: Journal Article
PubMed ID: #22379097 DOI: 10.1128/JVI.07085-11
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2011-10-26 Entry Last Modified: 2012-08-29
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