Live influenza A/Victoria/75 (H3N2) virus vaccines: reactogenicity, immunogenicity, and protection against wild-type virus challenge

Abstract

Four live influenza A/Victoria/75 (H3N2) recombinant virus vaccines were administered intranasally to a total of 50 volunteers who had little or no detectable serum neutralizing antibody. A recombinant with ts-l[E] having a 38°C shut-off temperature caused febrile reactions or systemic reactions or both in 21% of the volunteers, but one with ts-1A2 having a 37°C shut-off temperature caused no illness. Two recombinants prepared with cold-adapted A/Ann Arbor/6/60 caused 9% febrile reactions or systemic reactions or both. Virus shedding occurred in a minority of the 50 volunteers, but 90% developed a serum neutralizing antibody response. Wild-type A/Victoria/75 virus challenge of 34 of the vaccinated volunteers and 12 others who had had prior natural A/Victoria/75 virus infection revealed similar and significant protection when compared with the 96% infection and 68% febrile illness or systemic illness or both observed in 25 unvaccinated volunteers with little or no serum antibody. These results encourage continued efforts toward development of live influenza virus vaccines.

Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold‐adapted vaccine recombinant in which vaccine‐associated illness occurred in normal volunteers

“…Three populations have been evaluated. Low-seropositive young adults Hrabar et al, 1977;Murphy et al, 1977, Murphy et al, 1981, Cate and Couch 1982, Clements et al, 1983, Clements et al, 1984aClements et al, 1986;Nicholson et al, 19871, young children who were free of antibody to the hemagglutinin and neuraminidase [Wright et al, 1982;Johnson et al, 19851, and to a limited degree, the elderly [Gorse et al, 19861 (Betts et al, unpublished observations). Although only a few H3N2 vaccines have been tested, most have been associated with low rates of reactogenicity.…”

“…One such potential vaccine is the Ca mutant of influenza developed by Maassab [Maassab, 19671. This virus has proven to be particularly valuable since the six "internal" genes from the Ca strain can be easily recombined with the genes coding for the current neuraminidase and hemagglutininyielding relevant vaccine [Kendal et al, 19811. Over the last several years, relevant recombinants have been undergoing investigation Hrabar et al, 1977;Murphy et al, 1981;Cate and Couch, 1982;Betts et al, 1985;Clements et al, 1986;Gorse et al, 1986;King et al, 1987;Nicholson et al, 19871. These vaccines have low rates of reactogenicity even in young children who are both hemagglutinin-and neuraminidase antibody-negative [Lazar et al , 1980;Wright et al, 1982;Belshe and VanVoris, 1984;Johnson et al, 1985;King et al, 1987).…”

Serologic assays for influenza surveillance, diagnosis and vaccine evaluation

“…Owing to the strain specificity of the MN assay, as well as the HI assay, it is critical that the virus used for testing is the same or very similar to the virus that caused the infection or elicited an antibody response through vaccination. Numerous studies have demonstrated the correlation between HI and MN results and the higher sensitivity of VN or MN assays, particularly for detection of antibodies to influenza B viruses [48][49][50].…”

Identification of sequence changes in the cold-adapted, live attenuated influenzavaccine strain, A/Ann Arbor/6/60 (H2N2)

“…They also were attenuated, immunogenic, and protective in challenge and field studies in humans (Davenport eta/., 1977;Hrabar etal., 1977;Murphy etaL, 1979Murphy etaL, , 1980Murphy etaL, , 1981Murphy etaL, , 1982Lazar et al, 1 980;Reeve eta/., 1 980b;Mortiz et al, 1980;Van Voorthuizen et aL, 1981; Cate and 1 To whom requests for reprints should be addressed. Couch, 1982;Clements et aL, 1983; Belshe and Van Voris, 1 984; Couch etaL, 1 986).…”