EFFICACY OF AN INFLUENZA HEMAGGLUTININ DIPHTHERIA TOXOID CONJUGATE VACCINE IN ELDERLY NURSING-HOME SUBJECTS DURING AN INFLUENZA OUTBREAK

Objective: To compare the efficacy of an influenza hemagglutinin-diphtheria toroid conjugate vaccine with the commercially available influenza hemagglutinin-subunit vaccine in preventing influenza in older adults living in a nursing home. Design: A prospective, randomized, double-blind vaccine trial with 5 months of follow-up after vaccination. Setting: Fourteen Wisconsin nursing homes. Participants: Nursing home residents at least 65 years old who were able to give informed consent and were free of malignancy and not receiving immunosuppressive therapy. Interventions: Participants received, by intramuscular injection, 0.5 mt of a trivalent influenza vaccine containing 15 mu g each of A/Leningrad/360/86 (H3N2), A/Taiwan/1/86 (H1N1), and B/Ann Arbor/1/86 (HA) or 0.5 mt of an influenza vaccine containing the same antigens conjugated to diphtheria toroid (HA-D). Measurements: Blood was obtained pre- and 1 month postvaccination to assess for any vaccine-induced antibody titer change. Clinical surveillance for respiratory illness was performed twice weekly for 5 months. A record was kept of all signs and symptoms of new respiratory illness, and a viral culture and acute and convalescent sera were obtained. Results: 204 participants received HA and 204 received HA-D. Both groups had similar baseline antibody levels to all influenza antigens. HA-D recipients seroconverted more frequently based on serum neutralizing activity (P < 0.05), had a greater increase in geometric mean titer (GMT), and sustained the increase in antibody titer longer than HA recipients. Vaccine hemagglutinin recall was greater in a subset of HA-D recipients as measured by lymphocyte proliferative assays (P < 0.05). During an outbreak of influenza A (H3N2 A/Shanghai/11/87-like and A/Victoria/7/87-like), fewer HA-D (29/195) than HA (43/204) recipients had laboratory-confirmed infection (P = 0.053), and, of these, fewer HA-D-treated subjects had lower respiratory tract involvement (5/29 HA-D and 17/43 HA) (P = 0.022). Conclusions: HA-D was more immunogenic in institutionalized elderly recipients and produced greater protection from influenza infection. Superior protection may be due to HA-D's ability to stimulate and recruit antigen-presenting cells, thus enabling the recipient to achieve and maintain functional antibody titers.