Evaluation of Influenza A/Hong Kong/123/77 (H1N1) ts-1A2 and Cold-Adapted Recombinant Viruses in Seronegative Adult Volunteers |
| |
| Authors: | Brian R. Murphy Margret B. Rennels R. Gordon Douglas Jr. Robert F. Betts Robert B. Couch Thomas R. Cate Jr. Robert M. Chanock Alan P. Kendal Hunien F. Maassab Surapol Suwanagool Steven B. Sotman Luis A. Cisneros William C. Anthony David R. Nalin Myron M. Levine |
| |
| Affiliation: | Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20205;2.Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland 21201;University of Rochester School of Medicine, Rochester, New York 14627;Baylor College of Medicine, Houston, Texas 77000;Center for Disease Control, Atlanta, Georgia 30333;Department of Epidemiology, University of Michigan, School of Public Health, Ann Arbor, Michigan 43104 |
| |
| Abstract: | 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 ca recombinants 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 105.0 50% tissue culture infective doses. The virus shed by the ts-1A2 and ca vaccinees retained the ts or ca phenotype, or both. This occurred despite replication of the recombinant viruses for up to 9 days. No evidence for transmission of the ca or 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 ca vaccinees given 300 HID50 and approximately 70% of ca or ts vaccinees who received 10 to 32 HID50 of 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 ts and ca recombinants. |
| |
| Keywords: | |
|
|
