Safety and Immunogenicity of a Prepandemic Influenza A (H5N1) Vaccine in Children

Vajó, Zoltán; Kosa, Lajos; Szilvasy, Istvan; Pauliny, Zsuzsanna; Bartha, Kalman; Visontay, Ildiko; Kis, Agnes; Tarján, I; Rózsa, Noémi; Jankovics, István

doi:10.1097/inf.0b013e3181861dd7

Cited by 25 publications

(19 citation statements)

References 14 publications

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“…Our findings agree with those of a previous trial of the present vaccine, which found it to be immunogenic after a single dose of 6 g in 146 adults (24). We are now extending these studies to children, as a trial with a 6-g dose of the present vaccine in pediatric subjects was recently completed (26). Also, studies of cross-reactive immunity in a subset of the present study population were recently published (9).…”

Section: Discussionsupporting

confidence: 81%

A Single-Dose Influenza A (H5N1) Vaccine Safe and Immunogenic in Adult and Elderly Patients: an Approach to Pandemic Vaccine Development

Vajó

Wood

Kosa³

et al. 2010

J Virol

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With the ongoing pandemic of influenza A (H1N1) virus infection and the threat of high fatality rates for recent human cases of infection with highly pathogenic H5N1 strains, there has been considerable interest in developing pandemic vaccines. Here we report a randomized multicenter dose-finding clinical trial of a whole-virion, inactivated, adjuvanted H5N1 vaccine in adult and elderly volunteers. Four hundred eighty patients were randomly assigned to receive one or two doses of 3.5 g of the vaccine or one dose of 6 or 12 g. The subjects were monitored for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition and microneutralization tests. The subjects developed antibody responses against the influenza A (H5N1) virus. Single doses of >6 g fulfilled EU and U.S. licensing criteria for interpandemic and pandemic influenza vaccines. Except for occasional injection site pain, malaise, and fever, no adverse events were observed. We found that the present vaccine is safe and immunogenic in healthy adult and elderly subjects and requires low doses and, unlike any other H5N1 vaccines, only one injection to trigger immune responses which comply with licensing criteria. A vaccine using the same methods as those described in this report, but based on a wild-type swine-origin 2009 (H1N1) influenza A virus isolate from the United States (supplied by the CDC), has been developed and is currently being tested by our group.With the ongoing pandemic of influenza A (H1N1) virus infection and the threat of high fatality rates for recent human cases of infection with highly pathogenic H5N1 strains, there has been considerable interest in developing pandemic influenza vaccines.With new cases continuing to emerge, as of June 2009, the avian influenza A (H5N1) virus subtype has caused 433 human infections in 15 countries, as confirmed by the World Health Organization (WHO), resulting in severe illness with a high fatality rate (30). Human-to-human spread has been strongly suspected and even evidenced by statistical methods (22,33). With new human infections continuing to develop, this subtype continues to represent a potential source of an influenza pandemic (33).Mass vaccination is the most effective approach to reduce illness and death from pandemic influenza. Therefore, vaccine producers are currently developing and assessing vaccines against H5N1 viruses (2,14,31). The effects of split, subvirion, and whole-virion H5N1 vaccines have been tested, with various immunogenicity results (31). Three whole-virion vaccines have been tested so far, two of which required two-dose regimens (4, 14), while a one-dose regimen with the present vaccine was found to be immunogenic in 146 adult subjects (24).The objective of the present study was to determine the safety and immunogenicity of an inactivated whole-virion vaccine against influenza A/Vietnam/1194/2004, using multiple dosing and administration schedules, for adult and elderly subjects. To date, this is the only influenza pandemic prototy...

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Section: Discussionsupporting

confidence: 81%

A Single-Dose Influenza A (H5N1) Vaccine Safe and Immunogenic in Adult and Elderly Patients: an Approach to Pandemic Vaccine Development

Vajó

Wood

Kosa³

et al. 2010

J Virol

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“…The reduced-dose vaccine (Fluval K, an inactivated, wholevirion, trivalent vaccine with 6 g of HA/strain/0.5 ml content and aluminum phosphate gel adjuvant; lot no. FL-K-004) was produced by Omninvest Ltd. (Budapest, Hungary) as described previously (8,(14)(15)(16)(17)(18)(19). With the exception of the antigen amount, the vaccine was prepared by the same method as for the licensed seasonal influenza vaccine Fluval AB (19) and the licensed prepandemic vaccine Fluval H5N1 and the licensed pandemic H1N1 vaccine Fluval P (8,(14)(15)(16)(17)(18).…”

Section: Methodsmentioning

confidence: 99%

“…Typical trivalent seasonal influenza vaccines are unadjuvanted split-virion or subunit vaccines and contain 15 g of hemagglutinin (HA) per virus strain. We recently tested aluminum phosphate-adjuvanted whole-virion, monovalent prepandemic H5N1 and pandemic H1N1 influenza vaccines with only 6 g of HA and found them to be safe and immunogenic in pediatric, adult, and elderly subjects (8,(14)(15)(16)(17)(18). We also found that doses of 3.5 g did not trigger sufficient immune responses, while doses of 12 g were not substantially more immunogenic than 6-g doses when using monovalent vaccines (15).…”

mentioning

confidence: 99%

A Reduced-Dose Seasonal Trivalent Influenza Vaccine Is Safe and Immunogenic in Adult and Elderly Patients in a Randomized Controlled Trial

Vajó

Tamás

Jankovics³

2012

Clin. Vaccine Immunol.

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cWith the recent pandemic of influenza A (H1N1) and vaccine shortages, there has been considerable interest in developing influenza vaccines with reduced doses, allowing for increased production capacity. Here we report a prospective, randomized, double-blind, single-center clinical trial of a reduced-dose whole-virion inactivated, adjuvanted influenza vaccine in adult and elderly volunteers. A total of 234 subjects, including 120 adults (18 to 60 years of age) and 114 elderly subjects (>60 years of age) were enrolled to receive either 6 g or the conventional 15-g dose of seasonal trivalent influenza vaccines. The subjects were followed for safety analysis, and serum samples were obtained to assess immunogenicity by hemagglutination inhibition testing. The subjects developed antibody responses against the seasonal influenza A virus H1N1 and H3N2 strains, as well as the seasonal influenza B virus included in the vaccines. Single doses of 6 g fulfilled licensing criteria for seasonal influenza vaccines. No significant differences in rates of seroconversion or seroprotection or in geometric mean titers were found between the two dosage levels. All adverse events were rare, mild, and transient. We found that the present reduced-dose vaccine is safe and immunogenic in healthy adult and elderly subjects and triggers immune responses that comply with licensing criteria.

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“…While the discrepency between a single dose or two doses for inducing a sufficient immune response in infants and children is yet to be elucidated, the recommendation has been for two doses in children. 86 Clinical trails in the elderly (>60 years) 80,85,87,88 and the very elderly (>75 years) 88 demonstrated that, as for young adults, a single dose of as little as 7.5 µg was safe and effective. The finding that an unadjuvanted single dose induces a sufficient level of immune response may be due to the presence of pre-existing cross-reactive antibodies 89 to H1N1 2009 that increase in prevalence with age [at baseline 29% of young adults (18-64 years), 44% for 65-74 year old and 63% at >75 years 88 ].…”

confidence: 99%

Pre-pandemic and pandemic influenza vaccines

Rockman¹,

Brown²

2010

Human Vaccines

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Safety and Immunogenicity of a Prepandemic Influenza A (H5N1) Vaccine in Children

Abstract: We confirmed our earlier findings of the present vaccine in adults showing encouraging safety and immunogenicity properties in children. Studies with the present vaccine in elderly subjects are underway.

Cited by 25 publications

References 14 publications

A Single-Dose Influenza A (H5N1) Vaccine Safe and Immunogenic in Adult and Elderly Patients: an Approach to Pandemic Vaccine Development

A Single-Dose Influenza A (H5N1) Vaccine Safe and Immunogenic in Adult and Elderly Patients: an Approach to Pandemic Vaccine Development

A Reduced-Dose Seasonal Trivalent Influenza Vaccine Is Safe and Immunogenic in Adult and Elderly Patients in a Randomized Controlled Trial

Pre-pandemic and pandemic influenza vaccines

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