Evaluation of A/Alaska/6/77 (H3N2) cold-adapted recombinant viruses derived from A/Ann Arbor/6/60 cold-adapted donor virus in adult seronegative volunteers

Abstract

The influenza A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) virus was evaluated as a donor of attenuating genes to new variants of influenza A virus. This ca donor virus was mated with the A/Alaska/6/77 (H3N2) wild-type virus, and three A/Alaska/6/77 (H3N2) ca recombinant viruses were produced. The parental origin of the genes in the three ca recombinants had been determined previously (2), and their virulence for adult seronegative volunteers was assessed in the present study to identify the genes present in the ca donor virus that confer attenuation. Each of the recombinants received the hemagglutinin and neuraminidase genes from the A/Alaska/6/77 (H3N2) wild-type parent. One ca recombinant (CR-29) received all six transferable genes from the ca parent and was found to be satisfactorily attenuated in the volunteers. The two other ca recombinants received five of the six transferable genes with a wild-type gene at the M or NS locus. The pattern of infection in humans with these latter two ca recombinants was similar to the CR-29 ca recombinant. These findings demonstrate that inheritance of a gene in ca recombinants at the M or NS locus segregates independently of attenuation and suggest that the M and NS genes present in the ca donor virus are not the major determinants of attenuation conferred by this virus.

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[Wright et al, 1982;Johnson et al, 19851, and to a limited degree, the elderly [Gorse et al, 19861 (Betts et al, unpublished observations).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).…”

Effect of Antipyretic Therapy on the Duration of Illness in Experimental Influenza A, Shigella sonnei, and Rickettsia rickettsii Infections

“…Data derived from volunteers enrolled in six similar influenza A studies were analyzed. 6 The studies involved intranasal challenge with 10 4 or 10 6 TCID 50 (tissue culture 50% infectious dose) of five different strains of influenza A. Oral temperatures were measured every 6 hours.…”

Connecting within and between-hosts dynamics in the influenza infection-staged epidemiological models with behavior change

“…Following the bimodal behavior of viral load of the data, the mathematical model presented in Ref. [48], and studies of influenza virus infection, (59,60) we partitioned the profile of viral load into four stages with lengths 1, 2, 2, and 2 days, respectively for the four-stage model (Fig. 2).…”