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
Source: PubMed


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.

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    • "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 [68], [69]. 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.
    PLoS ONE 08/2011; 6(8):e23698. DOI:10.1371/journal.pone.0023698 · 3.23 Impact Factor

  • Periodontology 2000 03/1998; 16(1):53-79. DOI:10.1111/j.1600-0757.1998.tb00116.x · 3.63 Impact Factor
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    ABSTRACT: Immunization is the most feasible method for preventing influenza. Vaccination against influenza is recommended for everyone 65 years of age and older and for persons less than 65 years of age who are at risk for developing complications of influenza. Immune correlates of protection have been established, and a global network is in place to monitor the appearance and circulation of antigenic variants of influenza viruses, as well as the appearance of novel subtypes of influenza A. Antigenic and genetic analyses of circulating viruses and testing of serum from vaccine recipients guide vaccine composition updates. The efficacy of influenza vaccines depends in part on the closeness of the antigenic match between the vaccine strain and the epidemic strain. Currently licensed influenza vaccines are trivalent, formalin-inactivated, egg-derived vaccines; their efficacy ranges from 70 to 90% in young, healthy populations when there is a close antigenic match between vaccine strains and epidemic strains. Development of intranasally administered alternative vaccines and improvement of the existing vaccine are areas of active research. A trivalent, ca live vaccine is the most promising LAIV candidate. In a field trial, efficacy rates of LAIV in young children were 96% against influenza A (H3N2) and 91% against influenza B. However, few data are available to compare this formulation of the trivalent ca live vaccine with the trivalent, inactivated vaccine. Influenza vaccine recommendations will most likely be revised on licensure of LAIV; each vaccine may offer distinct advantages in specific populations.
    Advances in Virus Research 02/1999; 54:349-73. DOI:10.1016/S0065-3527(08)60371-1 · 4.57 Impact Factor
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