Low-Temperature-Adapted Influenza A2/AA/6/60 Virus Vaccine in Man

Kitayama, Toru; Togo, Yasushi; Hornick, Richard B.; Friedwald, William T.

doi:10.1128/iai.7.1.119-122.1973

Cited by 18 publications

(11 citation statements)

References 1 publication

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“…In support of this concept, a previous study of a cold-adapted, temperature-sensitive, attenuated A ⁄ Ann Arbor ⁄ 6 ⁄ 60 (H2N2) virus that had undergone less extensive passage in chicken cells was found to be immunogenic in seven of nine individuals when administered at a 30-fold lower dose (3AE0 · 10 5 TCID 50 ) in 1973. 11 It should be noted that in both the 1973 study and the present study, virus replication could not be detected following nasal administration. There are several possible explanations for these observations.…”

Section: Discussioncontrasting

confidence: 44%

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An open‐label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults

Talaat

Karron

Liang

et al. 2012

Influenza Resp Viruses

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Please cite this paper as: Talaat et al. (2012) An open‐label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults. Influenza and Other Respiratory Viruses DOI: 10.1111/j.1750‐2659.2012.00350.x. Background Live attenuated influenza vaccines (LAIV) against a variety of strains of pandemic potential are being developed and tested. We describe the results of an open‐label phase I trial of a live attenuated H2N2 virus vaccine. Objectives To evaluate the safety, infectivity, and immunogenicity of a live attenuated H2N2 influenza virus vaccine. Participants/methods The A/Ann Arbor/6/60 (H2N2) virus used in this study is the attenuated, cold‐adapted, temperature‐sensitive strain that provides the genetic backbone of seasonal LAIV (MedImmune). We evaluated the safety, infectivity, and immunogenicity of two doses of 107 TCID50 of this vaccine administered by nasal spray 4 weeks apart to normal healthy seronegative adults. Results Twenty‐one participants received a first dose of the vaccine; 18 participants received a second dose. No serious adverse events occurred during the trial. The most common adverse events after vaccination were headache and musculoskeletal pain. The vaccine was restricted in replication: 24% and 17% had virus detectable by culture or rRT‐PCR after the first and second dose, respectively. Antibody responses to the vaccine were also restricted: 24% of participants developed an antibody response as measured by either hemagglutination‐inhibition assay (10%), or ELISA for H2 HA‐specific serum IgG (24%) or IgA (16%) after either one or two doses. None of the participants had a neutralizing antibody response. Vaccine‐specific IgG‐secreting cells as measured by enzyme‐linked immunospot increased from a mean of 0·5 to 2·0/106 peripheral blood mononuclear cells (PBMCs); vaccine‐specific IgA‐secreting cells increased from 0·1 to 0·5/106 PBMCs. Conclusions The live attenuated H2N2 1960 AA ca vaccine demonstrated a safety profile consistent with seasonal trivalent LAIV but was restricted in replication and minimally immunogenic in healthy seronegative adults.

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Section: Discussioncontrasting

confidence: 44%

“…The virus was evaluated in 13 human subjects who had low to moderate levels of pre-existing antibody to A ⁄ AA ⁄ 6 ⁄ 60 influenza. 11 A dose of 3AE0 · 10 5 TCID 50 of the virus was immunogenic in seven of eight individuals with low levels of pre-existing antibody.…”

Section: Introductionmentioning

confidence: 92%

An open‐label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults

Talaat

Karron

Liang

et al. 2012

Influenza Resp Viruses

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“…The selection of mutant viruses that replicate efficiently at suboptimal temperatures has yielded viruses that are attenuated for animals and humans (2,4,8,(10)(11)(12)(13)(14) and, for this reason, the use of cold-adapted (ca) mutants of influenza A virus as vaccine strains for humans has been proposed (8). Initially, ca mutants of influenza A viruses were produced by successive passage at progressively lower temperature or by plaque selection after abrupt shift of incubation temperature from 33 to 250C (10,13).…”

mentioning

confidence: 99%

“…Initially, ca mutants of influenza A viruses were produced by successive passage at progressively lower temperature or by plaque selection after abrupt shift of incubation temperature from 33 to 250C (10,13). Alternative techniques for producing a vaccine strain after the emergence of a new epidemic or pandemic strain were sought for two reasons: (i) the time needed to produce a ca mutant virus of a new variant is at least 3 months, which is too long an interval in the face of an influenza virus epidemic (13); and (ii) ca mutants generated by this technique are heterogeneous with respect to in vitro properties (23) and to the level of attenuation for humans (2,4,8,13,25). Therefore, this approach could not be relied upon to rapidly produce a suitably attenuated vaccine strain of a new variant.…”

mentioning

confidence: 99%

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

et al. 1979

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Influenza A/Scotland/74 (H3N2) and A/Victoria/75 (H3N2) cold-adapted (ca) recombinant viruses, prepared by mating the A/Ann Arbor/6/60 (H2N2) ca donor virus and influenza A wild-type virus, were evaluated in adult seronegative volunteers (serum hemagglutination-inhibiting antibody titer, 51:8) for level of attenuation, antigenicity, and genetic stability of the temperature-sensitive and ca phenotypes. At 107.0 to 107-5 50% tissue culture infective doses the A/Scotland/74 and A/Victoria/75 ca recombinant viruses were clearly attenuated and antigenic. However, one of eight vaccinees infected with 107-5 50% tissue culture infective doses of the A/Scotland/74 ca recombinant had a febrile reaction (390C). At a 10-fold higher dose (108.5 50% tissue culture infective doses), 4 of 12 A/Scotland/74 vaccinees had a febrile and/or systemic reaction. Febrile reactions were not observed in volunteers who received the A/Victoria/75 ca recombinant virus, whereas 3 of the 12 vaccinees had mild upper respiratory tract symptoms, in one instance associated with mild systemic manifestations. Significantly, the serum hemagglutinationand neuraminidase-inhibiting antibody responses were comparable to those induced by wild-type virus. Both ca recombinant viruses were shed in low titer for a short period of time. Each isolate retained the temperature-sensitive phenotype. However, there was evidence of genetic instability of the ca marker in that 7 of 24 isolates exhibited some loss of the ca property, and one isolate completely lost the capacity to produce plaques at 25CC.

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“…2). Other markers examined are the ability to replicate well only in the turbinates (but poorly in the lungs), to have low reactogenicity, and not to revert in ts or ca phenotypes [14,28]. When ferret inoculum is in the range of 107-°-108-° EIDso the viruses were, with rare exception, restricted to growth in turbinates, and genetically stable ( Table 7).…”

Section: Biological Properties Of Recombinant Ca Virusesmentioning

confidence: 99%

Development of cold-adapted recombinant live, attenuated influenza A vaccines in the U.S.A. and U.S.S.R.

et al. 1982

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Low-Temperature-Adapted Influenza A2/AA/6/60 Virus Vaccine in Man

Cited by 18 publications

References 1 publication

An open‐label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults

An open‐label phase I trial of a live attenuated H2N2 influenza virus vaccine in healthy adults

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

Development of cold-adapted recombinant live, attenuated influenza A vaccines in the U.S.A. and U.S.S.R.

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