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Temperature-Sensitive Mutants of Influenza A Virus. XIV. Production and Evaluation of Influenza A/Georgia/74-ts-I[E] Recombinant Viruses in Human Adults

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Temperature-Sensitive Mutants of Influenza A Virus. XIV. Production and Evaluation of Influenza A/Georgia/74-ts-I[E] Recombinant Viruses in Human Adults

Auteurs : Douglas D. Richman [États-Unis] ; Brian R. Murphy [États-Unis] ; Robert B. Belshe [États-Unis] ; Harold M. Rusten [États-Unis] ; Robert M. Chanock [États-Unis] ; Neil R. Blacklow [États-Unis] ; Thomas A. Parrino [États-Unis] ; Frederick B. Rose [États-Unis] ; Myron M. Levine [États-Unis] ; Ellis Caplan [États-Unis]

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RBID : ISTEX:55B3969571E2E6D53CF2B61C1C8DAC704A21654B

Abstract

The two temperature-sensltlve (ts) lesions present in influenza A/Hong Kong/68-ts- 1[E] (H3N268) virus were transferred via genetic reassortment to influenza A/Georgia/74 (H3N274) wild-type virus. A recombinant clone possessing both ts lesions and the shutoff temperature of 38 C of the Hong Kong/68 ts donor and the two surface antigens of the Georgia/74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipient virus was a cloned population that induced illness in five of six infected volunteers. Therefore, the attenuation exhibited by the Georgia/74-ts-l[E] virus could reasonably be assumed to be due to the acquisition of the two ts-1[E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-l [E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kong/68-ts-1[E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombinant exhibited a similar, satisfactory level of attenuation and antigenicity for adults. It seems likely that the transfer of the ts-1[E] lesions to any new influenza virus will regularly result in attenuation of a recombinant virus possessing the new surface antigens.

Url:
DOI: 10.1093/infdis/136.2.256


Affiliations:


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<div type="abstract">The two temperature-sensltlve (ts) lesions present in influenza A/Hong Kong/68-ts- 1[E] (H3N268) virus were transferred via genetic reassortment to influenza A/Georgia/74 (H3N274) wild-type virus. A recombinant clone possessing both ts lesions and the shutoff temperature of 38 C of the Hong Kong/68 ts donor and the two surface antigens of the Georgia/74 wild-type virus was administered to 32 seronegative adult volunteers. Thirty-one volunteers were infected, of whom only five experienced mild afebrile upper respiratory tract illness. The wild-type recipient virus was a cloned population that induced illness in five of six infected volunteers. Therefore, the attenuation exhibited by the Georgia/74-ts-l[E] virus could reasonably be assumed to be due to the acquisition of the two ts-1[E] lesions by the Georgia/74 wild-type virus. The serum and nasal wash antibody responses of the ts-l [E] vaccinees were equivalent to those of the volunteers who received wild-type virus. The two ts lesions present in the Hong Kong/68-ts-1[E] virus have now been transferred three times to a wild-type virus bearing a new hemagglutinin, and in each instance the new ts recombinant exhibited a similar, satisfactory level of attenuation and antigenicity for adults. It seems likely that the transfer of the ts-1[E] lesions to any new influenza virus will regularly result in attenuation of a recombinant virus possessing the new surface antigens.</div>
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