Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: phase I randomised trial

Stephenson, Iain; Nicholson, Karl G.; Glück, Reinhardt; Mischler, Robert; Newman, Robert W.; Palache, Abraham; Verlander, Neville Q.; Warburton, Fiona; Wood, John M.; Zambon, Maria

doi:10.1016/s0140-6736(03)15014-3

Cited by 139 publications

(111 citation statements)

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“…54,58,[60][61][62][63][64][65][66][67] Lin et al 68 showed that a two-dose regimen of an aluminium hydroxide-adjuvanted whole-virion A/Vietnam/1194/2004 (H5N1) vaccine containing 10 µg of HA met all CHMP regulatory requirements for annual licensing of seasonal influenza vaccine. Ehrlich et al 60 evaluated WV A/Vietnam/1203/2004 (H5N1) vaccine (manufactured by Baxter Healthcare) at doses of 3.75, 7.5, 15 or 30 g of HA with an alum adjuvant, and 7.5 or 15 µg without an adjuvant.…”

Section: Immunogenicity Of Wholevirion Vaccines and Vaccines Adjuvantmentioning

confidence: 99%

“…However, in people aged 32 years or younger, WV vaccine produced a significantly higher probability of seroconversion than with subunit virus for this age group. 58 Nicholson et al 54 evaluated two doses of subunit A/Duck/Singapore/97 (H5N3) vaccine containing 3.75, 7.5 and 15 µg of HA with and without MF59 oil-in-water adjuvant. In this Phase I randomised trial, the GMTs of antibody and SCRs were significantly higher with MF59 adjuvanted vaccine.…”

Section: Immunogenicity Of Wholevirion Vaccines and Vaccines Adjuvantmentioning

confidence: 99%

“…Stephenson et al 58 evaluated two 7.5-, 15-and 30-µg doses of plain, subunit, influenza A/Hong Kong/1073/99 (H9N2) vaccines. The CHMP criterion for a > 2.5-fold increase in HI antibody titres was met after the second dose, but 86% vaccinees failed to attain protective levels of antibody.…”

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confidence: 99%

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A randomised, partially observer blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart

Nicholson

Abrams²,

Batham³

et al. 2010

Health Technol Assess

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A randomised, partially observer-blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart KG Participants: Three hundred and forty-seven subjects were identified and randomised to AS03 A -adjuvanted split-virion H1N1 vaccine or whole-virion (WV) vaccine in age groups [≥ 18-44 years (n = 140), ≥ 45-64 years (n = 136) and ≥ 65 years (n = 71)]. Interventions: Vaccine was administered by intramuscular injection into the deltoid muscle of the non-dominant arm. One hundred and seventy-five randomised subjects were allocated AS03 A -adjuvanted split H1N1 vaccine; one hundred and sixty-nine subjects had a second dose of the same vaccine 21 days later. One hundred and seventy-two subjects were allocated WV vaccine; one hundred and seventy-one subjects had a second dose of the same vaccine 21 days later. Serum samples for antibody measurements were collected on days 0 (before the first vaccination), 7, 14, 21 (before the second vaccination), 28, 35, 42 and 180. Subjects were observed for local and systemic reactions for 30 minutes after each injection, and for the next 7 days they recorded, in self-completed diaries, the severity of solicited local (pain, bruising, erythema and swelling) and systemic symptoms (chills, malaise, muscle aches, nausea and headache), oral temperature and use of analgesic medications. Main outcome measures: Vaccine immunogenicity using the CHMP and the FDA licensing criteria. Antibody titres were measured using haemagglutination inhibition (HI) and microneutralisation (MN) assays at baseline and 7, 14 and 21 days after each vaccination and at day 180. The three immunogenicity criteria end points were the seroprotection rate, the seroconversion rate and the mean-fold titre elevation. Results: Both vaccine doses were given in 340 subjects (98%). Data from 680 (99%) of 687 issued diary cards were returned. Sera were obtained from 340 (98.0%), 333 (96.0%), 341 (98.3%), 331 (95.4%), Abstract 196 329 (94.8%) and 332 (95.7%) subjects on days 7, 14, 21, 28, 35 and 42, respectively. Three hundred and fortysix and 345 subjects were included in the safety and immunogenicity analyses, respectively. Prevaccination antibody was detected by HI (titre ≥ 1 : 8) and MN (titre ≥ 1 : 10) in 14% and 31% of subjects, respectively. Among the 298 (85.9%) subjects without baseline antibody on HI assay, a titre of ≥ 1 : 40 (seroprotection) was achieved after a single dose of AS03 A -adjuvanted vaccine and WV vaccine by day 21 in 93.0% and 65.5%, respectively, of subjects between 18 and 44 years, 76.4% and 36.1% of subjects between 45 and 64 years, and 53.1% and 30.0% of subjects ≥ 65 years. Among all 347 subjects, a titre of ≥ 1 : 40 was achieved after a single dose of AS03 A -adjuvanted vaccine and WV vaccine by day 21 in 94.0% and 71.4%, respectively, of subjects between 18 and 44 years, 77.3% and 38.8% of subjects between 45 and 64 years, and 51.4% and 32.4% of subjects ≥ 65 years. The age-adjusted odds ratio (OR) for ...

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Section: Immunogenicity Of Wholevirion Vaccines and Vaccines Adjuvantmentioning

confidence: 99%

Section: Immunogenicity Of Wholevirion Vaccines and Vaccines Adjuvantmentioning

confidence: 99%

See 1 more Smart Citation

A randomised, partially observer blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart

Nicholson

Abrams²,

Batham³

et al. 2010

Health Technol Assess

View full text Add to dashboard Cite

show abstract

“…Recently, the urgency for developing pandemic influenza vaccines has been highlighted by a number of avian subtypes crossing the species barrier into man [13,14]. Vaccine containing avian influenza subtypes (H5 and H9) has proven to be poorly immunogenic in man [15][16][17], and this has led to the re-evaluation of the use of whole influenza virus vaccine.…”

Section: Introductionmentioning

confidence: 99%

Two Doses of Parenterally Administered Split Influenza Virus Vaccine Elicited High Serum IgG Concentrations which Effectively Limited Viral Shedding upon Challenge in Mice

2005

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We have previously found that whole influenza virus vaccine induced a more rapid and stronger humoral response, particularly after the first dose of vaccine, than split virus vaccine in mice. In this study, we have evaluated the protective efficacy of whole and split influenza virus vaccines in mice using a nonlethal upper respiratory tract challenge model. We have also investigated the immunological correlates associated with no or very little viral shedding after viral challenge. Vaccination resulted in reduced viral shedding and shortened the duration of infection by at least 2 days. After one dose of vaccine, whole virus vaccine generally resulted in less viral shedding than split virus vaccine. In contrast, two doses of split virus vaccine, particularly the highest vaccine strengths of 15 and 30 mg HA, most effectively limited viral replication and these mice had high concentrations of prechallenge influenza-specific serum IgG. The vaccine formulation influenced the IgG2a/IgG1 ratio, and this IgG subclass profile was maintained upon challenge to some extent, although it did not influence the level of viral shedding. The concentration of postvaccination serum IgG showed an inverse relationship with the level of viral shedding after viral challenge. Therefore, serum IgG is an important factor in limiting viral replication in the upper respiratory tract upon challenge of an antigenically similar virus.

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“…Although virus transmission from person to person is as yet minimal, 2 human viral infections have the potential of developing into the source of the next influenza pandemic, therefore the development of effective vaccines against the influenza A (H5N1) virus is a matter of considerable urgency. Previous work suggests that, in naïve humans, whole‐virion vaccine formulations are more immunogenic than subunit formulations and the use of adjuvants improves immunogenicity 3 , 4 , 5 , 6 , 7 , 8 , 9 …”

Section: Introductionmentioning

confidence: 99%

Characterization of a whole, inactivated influenza (H5N1) vaccine

Tada

2008

Influenza Resp Viruses

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Objectives Effective vaccines against the highly pathogenic influenza A/H5N1 virus are being developed worldwide. In Japan, two adjuvanted, inactivated, whole‐virion influenza vaccines were recently developed and licensed as mock‐up, pre‐pandemic vaccine formulations by the Ministry of Health and Labor Welfare of Japan. During the vaccine design and development process, various obstacles were overcome and, in this report, we introduce the non clinical production, immunogenicity data in human and development process that was associated with egg‐derived adjuvanted, inactivated, whole‐virion influenza A (H5N1) vaccine. Design Pilot lots of H5N1 vaccine were produced using the avirulent H5N1 reference strain A/Vietnam/1194/2004 (H5N1) NIBRG‐14 and administered following adsorption with aluminum hydroxide as an adjuvant. Quality control and formulation stability tests were performed before clinical trials were initiated (phase I‐III). The research foundation for microbial diseases of Osaka University (BIKEN) carried out vaccine production, quality control, stability testing and the phase I clinical trial in addition to overseeing the licensing of this vaccine. Mitsubishi Chemical Safety Institute Ltd. carried out the non clinical pharmacological toxicity and safety studies and the Japanese medical association carried out the phase II/III trials. Phase I‐III trials took place in 2006. Results The production processes were well controlled by established tests and validations. Vaccine quality was confirmed by quality control, stability and pre‐clinical tests, and the vaccine was approved as a mock‐up, pre‐pandemic vaccine by the Ministry of Health and Labor Welfare of Japan. Conclusions Numerous safety and efficacy procedures were carried out prior to the approval of the described vaccine formulation. Some of these procedures were of particular importance e.g., vaccine development, validation, and quality control tests that included strict monitoring of the hemagglutinin (HA) content of the vaccine formulations. Improving vaccine productivity, shortening the production period and improving antigen yield of the avirulent vaccine strains were also considered important vaccine development criteria.

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Safety and antigenicity of whole virus and subunit influenza A/Hong Kong/1073/99 (H9N2) vaccine in healthy adults: phase I randomised trial

Cited by 139 publications

References 14 publications

A randomised, partially observer blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart

A randomised, partially observer blind, multicentre, head-to-head comparison of a two-dose regimen of Baxter and GlaxoSmithKline H1N1 pandemic vaccines, administered 21 days apart

Two Doses of Parenterally Administered Split Influenza Virus Vaccine Elicited High Serum IgG Concentrations which Effectively Limited Viral Shedding upon Challenge in Mice

Characterization of a whole, inactivated influenza (H5N1) vaccine

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