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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
Author(s) -
Betts Robert F.,
Douglas R. Gordon,
Maassab Hunien F.,
Deborde Dan C.,
Clements Mary Lou,
Murphy Brian R.
Publication year - 1988
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.1890260209
Subject(s) - reactogenicity , virology , virus , titer , infectious dose , biology , attenuated vaccine , duck embryo vaccine , inoculation , medicine , immunology , virulence , immunization , antigen , gene , biochemistry , rabies virus
Live attenuated cold‐adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold‐adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten‐ and 100‐fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold‐adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID 50 ) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID 50 . We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.