Reduced infectivity of cold-adapted influenza A H1N1 viruses in the elderly: correlation with serum and local antibodies

Abstract

Objective: To compare young and elderly adults in terms of their immune responses and rates of infection following intranasal vaccination with a live attenuated influenza virus.

Design: Time series, comparing outcomes in young and elderly convenience sample.

Method: Retrospective laboratory analysis of serum and nasal wash specimens collected during prior studies in which young or elderly volunteers had been inoculated with cold-adapted influenza A/Kawasaki/86 (H1N1) reassortant virus.

Setting: Johns Hopkins Center for Immunization Research.

Participants: Healthy young and elderly adults with pre-vaccination serum hemagglutination inhibition (HAI) antibody titers less than or equal to 1:8.

Outcome measurements: Antibody responses in serum and nasal washes.

Main results: The proportion of vaccinees who developed any serum or local antibody response was higher in young compared with elderly subjects (20/20 vs 5/14, P less than 0.0005). Resistance to infection with cold-adapted virus correlated with pre-vaccination levels of serum immunoglobulin G (IgG), serum IgA, and nasal wash IgA antibody to whole virus antigen. Age was highly correlated with a lack of response to vaccine by simple regression, but not when data were adjusted for pre-existing antibody levels.

Conclusions: Cold-adapted reassortant influenza A H1N1 viruses achieve lower rates of infection in elderly than young adults, primarily due to age-related differences in preexisting levels of immunity which may not be reflected by HAI titer.