Antigenically Distinct MF59-Adjuvanted Vaccine to Boost Immunity to H5N1

Stephenson, Iain; Nicholson, Karl G.; Höschler, Katja; Zambon, Maria; Hancock, Kathy; DeVos, Joshua; Katz, Jacqueline M.; Praus, Michaela; Banzhoff, Angelika

doi:10.1056/nejmc0805274

Cited by 95 publications

(55 citation statements)

References 5 publications

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“…Preliminary findings indicated that cross-reactive hemagglutination-inhibition (HI) responses were induced following the booster vaccination (14). Here, we describe safety and immunogenicity data and show that earlier priming induced a pool of memory B cells that rapidly expanded after a single booster dose, resulting in neutralizing antibodies to antigenically diverse wild-type H5N1 viruses.…”

mentioning

confidence: 83%

Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine

Galli

Hancock

Höschler³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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However, at day 21 after boosting, MF59-adjuvanted primed subjects displayed a higher frequency of H5N1-specific memory B cells than plain-primed or unprimed subjects. The immune memory was rapidly mobilized by a single vaccine administration and resulted in high titers of neutralizing antibodies to antigenically diverse clade 0, 1, and 2 H5N1 viruses already at day 7. In general, postvaccination antibody titers were significantly higher in primed subjects than in unprimed subjects. Subjects primed with MF59-adjuvanted vaccine responded significantly better than those primed with plain vaccine, most notably in early induction and duration of cross-reacting antibody responses. After 6 months, high titers of cross-reactive antibody remained detectable among MF59-primed subjects. We conclude that distant priming with clade 0-like H5N3 induces a pool of cross-reactive memory B cells that can be boosted rapidly years afterward by a mismatched MF59-adjuvanted vaccine to generate high titers of crossreactive neutralizing antibodies rapidly. These results suggest that pre-pandemic vaccination strategies should be considered.

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mentioning

confidence: 83%

Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine

Galli

Hancock

Höschler³

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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233

174

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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%

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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“… 54 The MF59‐adjuvanted H5N1 vaccine rapidly induced (within 7 days after one dose) cross‐reactive antibody responses against diverse influenza H5N1 viruses, including clades 1, 2·1, 2·2 and 2·3. Cross‐reactive immune responses were substantially higher among subjects who initially received the MF59‐adjuvanted H5N3 vaccine, compared with the non‐adjuvanted vaccine.…”

Section: Confronting Pandemic Influenzamentioning

confidence: 99%

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Banzhoff

Pellegrini

Giudice

et al. 2008

Influenza Resp Viruses

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Influenza is a major cause of worldwide morbidity and mortality through frequent seasonal epidemics and infrequent pandemics. Morbidity and mortality rates from seasonal influenza are highest in the most frail, such as the elderly, those with underlying chronic conditions and very young children. Antigenic mismatch between strains recommended for vaccine formulation and circulating viruses can further reduce vaccine efficacy in these populations. Seasonal influenza vaccines with enhanced, cross‐reactive immunogenicity are needed to address these problems and can confer a better immune protection, particularly in seasons were antigenic mismatch occurs. A related issue for vaccine development is the growing threat of pandemic influenza caused by H5N1 avian strains. Vaccines against strains with pandemic potential offer the best approach for reducing the potential impact of a pandemic. However, current non‐adjuvanted pre‐pandemic vaccines offer suboptimal immunogenicity against H5N1. For both seasonal and pre‐pandemic vaccines, the addition of adjuvants may be the best approach for providing enhanced cross‐reactive immunogenicity. MF59®, the first oil‐in‐water emulsion licensed as an adjuvant for human use, can enhance vaccine immune responses through multiple mechanisms. A trivalent MF59‐adjuvanted seasonal influenza vaccine (Fluad®) has shown to induce significantly higher immune responses to influenza vaccination in the elderly, compared with non‐adjuvanted vaccines, and to provide cross‐reactive immunity against divergent influenza strains. Similar results have been generated with a MF59‐adjuvanted H5N1 pre‐pandemic vaccine, which showed higher and broader immunogenicity compared with non‐adjuvanted pre‐pandemic vaccines.

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Antigenically Distinct MF59-Adjuvanted Vaccine to Boost Immunity to H5N1

Cited by 95 publications

References 5 publications

Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine

Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine

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

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

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Antigenically Distinct MF59-Adjuvanted Vaccine to Boost Immunity to H5N1

Cited by 95 publications

References 5 publications

Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine

Fast rise of broadly cross-reactive antibodies after boosting long-lived human memory B cells primed by an MF59 adjuvanted prepandemic vaccine

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

MF59®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis

Contact Info

Product

Resources

About

MF59^®‐adjuvanted vaccines for seasonal and pandemic influenza prophylaxis