Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans

Treanor, John J.; Wilkinson, Bethanie; Masseoud, Feda; Hu-Primmer, Jean; Battaglia, R; O'Brien, Diane; Wolff, Mark; Rabinovich, Gina; Blackwelder, William; Katz, Jacqueline M.

doi:10.1016/s0264-410x(00)00395-9

Cited by 310 publications

(211 citation statements)

References 17 publications

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“…Antisera generated by immunization with the VN1203 vaccine, prepared using the clade 1 strain Vietnam/1203/2002, not only neutralized a number of H5N1 clade 1 strains ranging from 1997 to 2004 isolates (differing in HA antigenicity [23][24][25]) but also neutralized the first clade 2 strain to emerge (Indonesia/05/2005) [15]. The baculovirus-derived recombinant HA antigen was less effective in inducing neutralizing antibodies against the clade 1 strains, and it did not induce neutralizing responses to the clade 2 strain, in agreement with reports that very high antigen doses of rHA were required to induce seroconversion in humans [16].…”

Section: Discussionsupporting

confidence: 83%

“…Moreover, substantial cross-neutralization was also seen with a H5N3 strain (A/Duck/Singapore-Q/F119-3/97) but, as expected, no activity was measured against a control H7N1 strain. Despite being administered in the guinea pigs at a higher concentration, the recombinant antigen induced lower neutralizing antibody titers to the homologous strain (VN1203) and was ineffective against the clade 2 IN5/05 strain, consistent with reports that very high antigen doses of rHA vaccine were required to induce seroconversion in human trials [16]. These data indicate that the candidate whole virus vaccine has the potential to be effective against a broad range of H5N1 viruses as antisera generated by immunization with the VN1203 vaccine not only neutralized a number of human pathogenic H5N1 clade 1 strains ranging from 1997 to 2004 but also the clade 2 Indonesia strain.…”

Section: Immunogenicity and Cross-neutralization In Guinea Pigssupporting

confidence: 87%

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Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Kistner

Howard

Spruth

et al. 2007

Vaccine

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The rapid spread and the transmission to humans of avian influenza virus (H5N1) has induced worldwide fears of a new pandemic and raised concerns over the ability of standard influenza vaccine production methods to rapidly supply sufficient amounts of an effective vaccine. We report here on a robust and flexible strategy which uses wild-type virus grown in a continuous cell culture (Vero) system to produce an inactivated whole virus vaccine. Candidate vaccines based on clade 1 and clade 2 influenza H5N1 strains were developed and demonstrated to be highly immunogenic in animal models. The vaccines induce cross-neutralising antibodies, highly cross-reactive T-cell responses and are protective in a mouse challenge model not only against the homologous virus but against other H5N1 strains, including those from another clade. These data indicate that cell culture-grown, whole virus vaccines, based on the wild-type virus, allow the rapid high yield production of a candidate pandemic vaccine.

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Section: Discussionsupporting

confidence: 83%

Section: Immunogenicity and Cross-neutralization In Guinea Pigssupporting

confidence: 87%

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Kistner

Howard

Spruth

et al. 2007

Vaccine

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“…A rapidly developing pandemic would shorten the timeframe to identify the viral strain and prepare an antigenically matched vaccine, while the need to vaccinate an entirely naïve population would exacerbate vaccine production and supply issues. In addition, H5 vaccine candidates, either H5 recombinant protein or a conventional surface antigen vaccine prepared from apathogenic H5N3 virus, have shown suboptimal immunogenicity in human trials (4,5). …”

mentioning

confidence: 99%

DNA Vaccine Expressing Conserved Influenza Virus Proteins Protective Against H5N1 Challenge Infection in Mice

Epstein

Tumpey

Misplon

et al. 2002

Emerg. Infect. Dis.

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Influenza vaccination practice, which is based on neutralizing antibodies, requires being able to predict which viral strains will be circulating. If an unexpected strain, as in the 1997 H5N1 Hong Kong outbreak, or even a pandemic emerges, appropriate vaccines may take too long to prepare. Therefore, strategies based on conserved influenza antigens should be explored. We studied DNA vaccination in mice with plasmids expressing conserved nucleoprotein (NP) and matrix (M) from an H1N1 virus. After vaccination, mice were challenged with A/H5N1 viruses of low, intermediate, and high lethality. A/NP+A/M DNA vaccination reduced replication of A/Hong Kong/486/97 (HK/486), a nonlethal H5N1 strain, and protected against lethal challenge with more virulent A/Hong Kong/156/97 (HK/156). After HK/156 exposure, mice survived rechallenge with A/Hong Kong/483/97 (HK/483), although the DNA vaccination alone protected poorly against this highly virulent strain. In the absence of antigenically matched hemagglutinin-based vaccines, DNA vaccination with conserved influenza genes may provide a useful first line of defense against a rapidly spreading pandemic virus.

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“…Trials using non‐adjuvanted egg‐grown subvirion H5N1 vaccine or recombinant H5 HA both demonstrated that very high antigen doses (90 μg HA) given twice were required to elicit a reasonable immune response 19 , 20 . For the egg‐grown vaccine such high doses are clearly unacceptable in view of the difficulty of satisfying a pandemic demand.…”

Section: Pandemic Vaccinesmentioning

confidence: 99%

Vaccines for an influenza pandemic: scientific and political challenges

Haaheim

2007

Influenza Resp Viruses

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So far, most published results from clinical trials using various avian influenza virus vaccine formulations have been disappointing. Should the pandemic strike, we still do not have the ability to provide an efficacious pandemic vaccine in time and in sufficient quantities for the world. The H5N1 enzootic could potentially give rise to a pandemic at any time. Transcontinental air traffic could seed the pandemic virus to most corners of the globe within a few weeks/months. We still have a unique window of opportunity to stimulate and support academia and the pharmaceutical industry to accelerate the urgently needed vaccine research. The political inertia is surprising, particularly as politicians, if and when a pandemic eventuates, will be asked why, despite repeated warnings, they did not take appropriate action in time. It is a governmental obligation – and not that of the WHO or the pharmaceutical industry – to protect their nationals. Moreover, when the poorer nations of this world realize that equitable quantities of the scarce supplies of vaccines, drugs and medical essentials will not come their way, the post‐pandemic international scene will be one of even more deep distrust for many years. This scenario is not acceptable.

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Safety and immunogenicity of a recombinant hemagglutinin vaccine for H5 influenza in humans

Cited by 310 publications

References 17 publications

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

Cell culture (Vero) derived whole virus (H5N1) vaccine based on wild-type virus strain induces cross-protective immune responses

DNA Vaccine Expressing Conserved Influenza Virus Proteins Protective Against H5N1 Challenge Infection in Mice

Vaccines for an influenza pandemic: scientific and political challenges

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