Autor: |
Murphy, Brian R., Rennels, Margret B., Douglas, R. Gordon, Betts, Robert F., Couch, Robert B., Cate, Thomas R., Chanock, Robert M., Kendal, Alan P., Maassab, Hunien F., Suwanagool, Surapol, Sotman, Steven B., Cisneros, Luis A., Anthony, William C., Nalin, David R., Levine, Myron M. |
Zdroj: |
Infection and Immunity; August 1980, Vol. 29 Issue: 2 p348-355, 8p |
Abstrakt: |
Two attenuated influenza A donor viruses, the A/Udorn/72 ts-1A2 and the A/Ann Arbor/6/60 cold-adapted (ca) viruses, are being evaluated for their ability to reproducibly attenuate each new variant of influenza A virus to a specific and desired level by the transfer of one or more attenuating genes. Each of these donor viruses has been able to attenuate influenza A viruses belonging to the H3N2 subtype by the transfer of one or more attenuating genes. To determine whether these two donor viruses could attenuate a wild-type virus that belonged to a different influenza A subtype, ts-1A2 and carecombinants of a wild-type virus representative of the A/USSR/77 (H1N1) Russian influenza strain were prepared and evaluated in adult doubly seronegative volunteers at several doses. The recombinants derived from both donor viruses were attenuated for the doubly seronegative adults. Less than 5% of infected vaccinees developed a febrile or systemic reaction, whereas five of six recipients of wild-type virus developed such a response. The 50% human infectious dose (HID50) for each recombinant was approximately 105.050% tissue culture infective doses. The virus shed by the ts-1A2 and cavaccinees retained the tsor caphenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the caor ts-1A2 recombinant virus to controls was observed. A serum hemagglutination inhibition response was detected in less than 50% of the infected vaccinees. However, with the more sensitive enzyme-linked immunosorbent assay, a serological response was detected in 100% of the cavaccinees given 300 HID50and approximately 70% of caor tsvaccinees who received 10 to 32 HID50of virus. These results indicate that the recombinants derived from both donor viruses were satisfactorily attenuated and were stable genetically after replication in doubly seronegative adults although they induced a lower serum hemagglutination inhibition response than that found previously for H3N2 tsand carecombinants. |
Databáze: |
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