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J Clin Microbiol. 1986 May; 23(5): 852–857.
PMCID: PMC268736

Evaluation of live avian-human reassortant influenza A H3N2 and H1N1 virus vaccines in seronegative adult volunteers.

Abstract

An avian-human reassortant influenza A virus deriving its genes coding for the hemagglutinin and neuraminidase from the human influenza A/Washington/897/80 (H3N2) virus and its six "internal" genes from the avian influenza A/Mallard/NY/6750/78 (H2N2) virus (i.e., a six-gene reassortant) was previously shown to be safe, infectious, nontransmissible, and immunogenic as a live virus vaccine in adult humans. Two additional six-gene avian-human reassortant influenza viruses derived from the mating of wild-type human influenza A/California/10/78 (H1N1) and A/Korea/1/82 (H3N2) viruses with the avian influenza A/Mallard/NY/78 virus were evaluated in seronegative (hemagglutination inhibition titer, less than or equal to 1:8) adult volunteers for safety, infectivity, and immunogenicity to determine whether human influenza A viruses can be reproducibly attenuated by the transfer of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The 50% human infectious dose was 10(4.9) 50% tissue culture infectious doses for the H1N1 reassortant virus and 10(5.4) 50% tissue culture infectious doses for the H3N2 reassortant virus. Both reassortants were satisfactorily attenuated with only 5% (H1N1) and 2% (H3N2) of infected vaccines receiving less than 400 50% human infectious doses developing illness. Consistent with this level of attenuation, the magnitude of viral shedding after inoculation was reduced 100-fold (H1N1) to 10,000-fold (H3N2) compared with that produced by wild-type virus. The duration of virus shedding by vaccines was one-third that of controls receiving wild-type virus. At 40 to 100 50% human infectious doses, virus-specific immune responses were seen in 77 to 93% of volunteers. When vaccinees who has received 10(7.5) 50% tissue culture infectious doses of the H3N2 vaccine were experimentally challenged with a homologous wild-type human virus only 2 of 19 (11%) vaccinees became ill compared with 7 of 14 (50%) unvaccinated seronegative controls ( P < 0.025; protective efficacy, 79%). Thus, three different virulent human influenza A viruses have been satisfactorily attenuated by the acquisition of the six internal genes of the avian influenza A/Mallard/NY/78 virus. The observation that this donor virus can reproducibly attenuate human influenza A viruses indicates that avian-human influenza A reassortants should be further studied as potential live influenza A virus vaccines.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Clements ML, Betts RF, Maassab HF, Murphy BR. Dose response of influenza A/Washington/897/80 (H3N2) cold-adapted reassortant virus in adult volunteers. J Infect Dis. 1984 May;149(5):814–815. [PubMed]
  • Clements ML, Betts RF, Murphy BR. Advantage of live attenuated cold-adapted influenza A virus over inactivated vaccine for A/Washington/80 (H3N2) wild-type virus infection. Lancet. 1984 Mar 31;1(8379):705–708. [PubMed]
  • Clements ML, O'Donnell S, Levine MM, Chanock RM, Murphy BR. Dose response of A/Alaska/6/77 (H3N2) cold-adapted reassortant vaccine virus in adult volunteers: role of local antibody in resistance to infection with vaccine virus. Infect Immun. 1983 Jun;40(3):1044–1051. [PMC free article] [PubMed]
  • Johnson PR, Jr, Feldman S, Thompson JM, Mahoney JD, Wright PF. Comparison of long-term systemic and secretory antibody responses in children given live, attenuated, or inactivated influenza A vaccine. J Med Virol. 1985 Dec;17(4):325–335. [PubMed]
  • Murphy BR, Buckler-White AJ, London WT, Harper J, Tierney EL, Miller NT, Reck LJ, Chanock RM, Hinshaw VS. Avian-human reassortant influenza A viruses derived by mating avian and human influenza A viruses. J Infect Dis. 1984 Dec;150(6):841–850. [PubMed]
  • Murphy BR, Chalhub EG, Nusinoff SR, Kasel J, Chanock RM. Temperature-sensitive mutants of influenza virus. 3. Further characterization of the ts-1(E) influenza A recombinant (H3N2) virus in man. J Infect Dis. 1973 Oct;128(4):479–487. [PubMed]
  • Murphy BR, Clements ML, Madore HP, Steinberg J, O'Donnell S, Betts R, Demico D, Reichman RC, Dolin R, Maassab HF. Dose response of cold-adapted, reassortant influenza A/California/10/78 virus (H1N1) in adult volunteers. J Infect Dis. 1984 May;149(5):816–816. [PubMed]
  • Murphy BR, Clements ML, Tierney EL, Black RE, Stienberg J, Chanock RM. Dose response of influenza A/Washington/897/80 (H3N2) avian-human reassortant virus in adult volunteers. J Infect Dis. 1985 Jul;152(1):225–229. [PubMed]
  • Murphy BR, Hinshaw VS, Sly DL, London WT, Hosier NT, Wood FT, Webster RG, Chanock RM. Virulence of avian influenza A viruses for squirrel monkeys. Infect Immun. 1982 Sep;37(3):1119–1126. [PMC free article] [PubMed]
  • Murphy BR, Holley HP, Jr, Berquist EJ, Levine MM, Spring SB, Maassab HF, Kendal AP, Chanock RM. Cold-adapted variants of influenza A virus: evaluation in adult seronegative volunteers of A/Scotland/840/74 and A/Victoria/3/75 cold-adapted recombinants derived from the cold-adapted A/Ann Arbor/6/60 strain. Infect Immun. 1979 Feb;23(2):253–259. [PMC free article] [PubMed]
  • Murphy BR, Nelson DL, Wright PF, Tierney EL, Phelan MA, Chanock RM. Secretory and systemic immunological response in children infected with live attenuated influenza A virus vaccines. Infect Immun. 1982 Jun;36(3):1102–1108. [PMC free article] [PubMed]
  • Murphy BR, Phelan MA, Nelson DL, Yarchoan R, Tierney EL, Alling DW, Chanock RM. Hemagglutinin-specific enzyme-linked immunosorbent assay for antibodies to influenza A and B viruses. J Clin Microbiol. 1981 Mar;13(3):554–560. [PMC free article] [PubMed]
  • Murphy BR, Sly DL, Tierney EL, Hosier NT, Massicot JG, London WT, Chanock RM, Webster RG, Hinshaw VS. Reassortant virus derived from avian and human influenza A viruses is attenuated and immunogenic in monkeys. Science. 1982 Dec 24;218(4579):1330–1332. [PubMed]
  • Phelan MA, Mayner RE, Bucher DJ, Ennis FA. Purification of influenza virus glycoproteins for the preparation and standardization of immunological potency testing reagents. J Biol Stand. 1980;8(3):233–242. [PubMed]
  • Webster RG, Yakhno M, Hinshaw VS, Bean WJ, Murti KG. Intestinal influenza: replication and characterization of influenza viruses in ducks. Virology. 1978 Feb;84(2):268–278. [PubMed]
  • Tian SF, Buckler-White AJ, London WT, Reck LJ, Chanock RM, Murphy BR. Nucleoprotein and membrane protein genes are associated with restriction of replication of influenza A/Mallard/NY/78 virus and its reassortants in squirrel monkey respiratory tract. J Virol. 1985 Mar;53(3):771–775. [PMC free article] [PubMed]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)