Effect of Age on Cytotoxic T Lymphocyte Memory as well as Serum and Local Antibody Responses Elicited by Inactivated Influenza Virus Vaccine

Abstract

Healthy seropositive adults aged < 40 (n = 15), 40-64 (n = 15), and > or = 65 (n = 17) years were parenterally immunized with trivalent subvirion influenza virus vaccine, and their cellular and humoral immune responses were compared. Vaccination resulted in a significant enhancement of class I human leukocyte antigen-restricted influenza A cross-reactive cytotoxic T lymphocyte (CTL) memory. Elderly subjects had significantly lower baseline and peak postvaccination mean percentages of specific lysis of influenza A virus-infected autologous targets but nonetheless mounted CTL responses to vaccine that were comparable in magnitude to those of younger adults. Serologic responses and nasal IgG responses to each of 3 vaccine strains were reduced in magnitude and frequency with advancing age. Parenteral immunization was ineffective at inducing nasal wash IgA antibodies. Between 2 and 12 weeks after vaccination, serum and nasal antibody titers decreased modestly, although the rate of decline was comparable between age groups. The ability of elderly adults to mount CTL responses after influenza vaccination suggests that T cell effector mechanisms may be an important determinant of vaccine-induced protection against serious illness in this age group.

Quantitative review of antibody response to inactivated seasonal influenza vaccines

“…We identified 60 eligible articles published between 1987 and 2006 describing inactivated seasonal influenza vaccine immunogenicity studies conducted in the United States, Canada, Europe, Israel, and Russia 10 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 . We included 129 independent study arms of which 119 reported data on response to A/H1N1, 109 on influenza B, and 108 on A/H3N2 vaccine strains (Table 1).…”

Lower GrB+ CD62Lhigh CD8 TCM effector lymphocyte response to influenza virus in older adults is associated with increased CD28null CD8 T lymphocytes

“…The reduced protection is believed to be due to poor stimulation of cellular immunity (Powers et al, 1993;McElhaney et al, 2006) and risk for influenza illness in vaccinated older adults is associated with low levels of granzyme (GrB), a key cytolytic mediator of the CTL response to influenza (McElhaney et al, 2001;Schmidt et al, 2004). This current study focused on age-related changes in the virus-specific memory CTL (CD8+) response to influenza that may explain the increased risk of influenza illness in older adults.…”

Cytolytic activity of mitogen activated old and young mouse spleen cells against tumor target cells expressing high or low levels of Fas antigen

“…These include T-cell proliferation in response to stimulation through T cell receptor and co-stimulators (Engwerda et al, 1994;Lerner et al, 1988;Song et al, 1993), production and response to growth promoting cytokines (Ernst et al, 1993;Nagelkerken et al, 1991;Saxena et al, 1988) and generation of cytotoxic T-cells (Hirano and Nordin, 1976;Powers and Belshe, 1993;Mbawuike et al, 1997). We have previously characterized mitogen induced cytotoxic spleen cells from young and old mice and reported differences in their cytolytic activities (Saxena et al, 1981(Saxena et al, , 1988a.…”