Evaluation of Cold-Adapted, Reassortant Influenza B Virus Vaccines in Elderly and Chronically III Adults
Department of Medicine, University of Rochester School of Medicine, New York 14642. The Journal of Infectious Diseases
(Impact Factor: 6).
02/1994; 169(2):402-7. DOI: 10.1093/infdis/169.2.402
The safety and immunogenicity of two recent cold-adapted reassortant influenza B viruses were evaluated in persons at high risk for influenza-related morbidity and mortality. Ambulatory adults > 65 years old or with chronic high-risk conditions were randomly assigned to receive parenteral trivalent inactivated influenza vaccine containing either influenza B/Ann Arbor/86 or B/Yamagata/88 hemagglutinin antigens, cold-adapted reassortant influenza B/Ann Arbor/1/86 or B/Yamagata/16/88 viruses (10(7.2) TCID50), or placebo in double-blind fashion. Cold-adapted vaccine viruses were well tolerated, with similar rates of respiratory symptoms in all groups. There were no changes in spirometry or oxygen saturation following vaccination. Immune responses to both types of vaccine were modest, with serum antibody responses occurring significantly more frequently and with higher magnitude in those receiving inactivated than in those receiving cold-adapted vaccine. Cold-adapted, reassortant influenza B vaccines are safe in the elderly and those with chronic illness but are not optimally immunogenic in this group.
Available from: PubMed Central
- "A live attenuated influenza vaccine (LAIV) has been approved for people aged 5–49 in the United States and was recently also approved for use in Canada. Although live vaccines are expected to be more efficient in inducing cross-protective T cell responses, no protective benefit was shown for LAIV-vaccinated individuals aged 50 and over , . It may be that LAIV may not provide additional protection to elderly individuals due to pre-existing IgA antibodies in the respiratory tract. "
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ABSTRACT: T cells specific for persistent pathogens accumulate with age and express markers of immune senescence. In contrast, much less is known about the state of T cell memory for acutely infecting pathogens. Here we examined T cell responses to influenza in human peripheral blood mononuclear cells from older (>64) and younger (<40) donors using whole virus restimulation with influenza A (A/PR8/34) ex vivo. Although most donors had pre-existing influenza reactive T cells as measured by IFNγ production, older donors had smaller populations of influenza-responsive T cells than young controls and had lost a significant proportion of their CD45RA-negative functional memory population. Despite this apparent dysfunction in a proportion of the older T cells, both old and young donors' T cells from 2008 could respond to A/California/07/2009 ex vivo. For HLA-A2+ donors, MHC tetramer staining showed that a higher proportion of influenza-specific memory CD8 T cells from the 65+ group co-express the markers killer cell lectin-like receptor G1 (KLRG1) and CD57 compared to their younger counterparts. These markers have previously been associated with a late differentiation state or immune senescence. Thus, memory CD8 T cells to an acutely infecting pathogen show signs of advanced differentiation and functional deterioration with age. There was a significant negative correlation between the frequency of KLRG1(+)CD57(+) influenza M1-specific CD8 T cells pre-vaccination and the ability to make antibodies in response to vaccination with seasonal trivalent inactivated vaccine, whereas no such trend was observed when the total CD8(+)KLRG1(+)CD57(+) population was analyzed. These results suggest that the state of the influenza-specific memory CD8 T cells may be a predictive indicator of a vaccine responsive healthy immune system in old age.
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ABSTRACT: We have evaluated the use of live cold-adapted influenza A and B virus vaccines in the elderly. Cold-adapted influenza A and B virus vaccines are safe and modestly immunogenic in individuals over 65 years of age. However, our studies and those of other groups have shown that immune response to cold-adapted vaccines in this age group are modest. Administration of combined cold-adapted influenza A and inactivated influenza vaccine has resulted in slightly higher frequencies of local and systemic humoral immune responses than inactivated vaccine alone in some, but not all, studies. In a double-blind field trial conducted in nursing homes over a 3 year period, combined cold-adapted influenza A (H3N2) and trivalent inactivated influenza vaccine resulted in a 60% decrease (95% CI, 18-82%) in the rate of laboratory documented influenza A compared with inactivated vaccine alone. Further studies of multivalent cold-adapted influenza vaccines used in combination with inactivated vaccine should be performed.
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