Meta-Analysis of the Immunogenicity and Tolerability of Pandemic Influenza A 2009 (H1N1) Vaccines

Abstract

BackgroundAlthough the 2009 (H1N1) influenza pandemic officially ended in August 2010, the virus will probably circulate in future years. Several types of H1N1 vaccines have been tested including various dosages and adjuvants, and meta-analysis is needed to identify the best formulation.MethodsWe searched MEDLINE, EMBASE, and nine clinical trial registries to April 2011, in any language for randomized clinical trials (RCTs) on healthy children, adolescents, adults and the elderly. Primary outcome was the seroconversion rate according to hemagglutinination-inhibition (HI); secondary outcomes were adverse events. For the primary outcome, we used head-to-head meta-analysis and multiple-treatments meta-analysis.ResultsEighteen RCTs could be included in all primary analyses, for a total of 76 arms (16,725 subjects). After 2 doses, all 2009 H1N1 split/subunit inactivated vaccines were highly immunogenic and overcome CPMP seroconversion criteria. After 1 dose only, all split/subunit vaccines induced a satisfactory immunogenicity (> = 70%) in adults and adolescents, while only some formulations showed acceptable results for children and elderly (non-adjuvanted at high-doses and oil-in-water adjuvanted vaccines). Vaccines with oil-in-water adjuvants were more immunogenic than both nonadjuvanted and aluminum-adjuvanted vaccines at equal doses and their immunogenicity at doses < = 6 µg (even with as little as 1.875 µg of hemagglutinin antigen) was not significantly lower than that achieved after higher doses. Finally, the rate of serious vaccine-related adverse events was low for all 2009 H1N1 vaccines (3 cases, resolved in 10 days, out of 22826 vaccinated subjects). However, mild to moderate adverse reactions were more (and very) frequent for oil-in-water adjuvanted vaccines.ConclusionsSeveral one-dose formulations might be valid for future vaccines, but 2 doses may be needed for children, especially if a low-dose non-adjuvanted vaccine is used. Given that 15 RCTs were sponsored by vaccine manufacturers, future trials sponsored by non-industry agencies and comparing vaccines using different types of adjuvants are needed.

Pandemic Influenza A(H1N1) in Cote d'Ivoire: health-care providers’ knowledge of influenza and attitudes towards vaccination

“…It is therefore essential to work towards a reduction in refusals to lower than 10% through further education and awareness campaigns. The main reasons given for refusal were the lack of information about the vaccine, doubts about efficacy, and fear of adverse effects, which are also factors mentioned in other publications [8][9][10][11]. These attitudes can easily be targeted by making available the data on tolerance and efficacy of the vaccine against pH1N1, which should reassure the skeptics and increase the interest for vaccination [2,43].…”

“…In addition, the Ivorian health authorities had not released any specific information about the vaccine against pandemic influenza A (H1N1) to health-care providers; this situation posed a real risk in implementing a successful vaccination campaign [4][5][6][7]. Reports questioning the efficacy and safety of the pandemic vaccine [8][9][10][11][12] led to low vaccination coverage in health-care providers in some countries [13][14][15]. In Sub-Saharan Africa, there was a general lack of data on influenza, including both epidemiological data as well as data on seasonal vaccination against influenza [16][17][18].…”

Non-publication and delayed publication of randomized trials on vaccines: a survey

“…1 In the case of emerging pandemics with modifying or even new infectious agents, such as the pandemic A/H1N1 2009 influenza virus, 2 the availability of information on potential vaccines becomes even more time sensitive. 3 While a time-lag in the dissemination of results may have adverse consequences for the practice of evidence based medicine and on public health for any disease, for epidemic diseases a delay in publication of relevant randomized controlled trials may distort the available evidence that is used for recommendations, allocation of resources, stockpiling of drugs and vaccines, and other public action.…”

Konzepte, Wirksamkeit und Perspektiven pandemischer und nichtpandemischer Influenzaimpfungen

“…In 2 Metaanalysen wurden die Ergebnisse von 18 RCTs (n>18.000 Impflinge) unabhängig voneinander zusammengefasst. Beide Analysen kamen zu vergleichbaren Resultaten [50,51]: In nahezu allen Studien erfüllten alle Spalt-und Untereinheitenimpfstoffe unabhängig von der Antigendosierung und Adjuvantierung in allen Altersgruppen (einschließlich Kinder und Impflinge über dem 65. Lebensjahr) die immunologischen Akzeptanzkriterien.…”

“…Bei Erwachsenen wird als Ursache hierfür das anfangs unerwartet hohe Ausmaß einer vorbestehenden Kreuzimmunität angenommen, das die Impfantwort im Sinne eines Boostereffekts begünstigt haben könnte [52]. Zusätzlich wird eine höhere Immunogenität des HA des Influenzavirus A/H1N1 (2009) diskutiert, die das Impfansprechen bei immunologisch naiven Kindern verbessert haben könnte [25,50]. Die Frage, ob in einem anderen Pandemieszenario eine der beiden Impfstoffstrategien der anderen überlegen gewesen wäre, kann man also auf Basis der Erfahrung aus der Influenzapandemie 2009 nicht beantworten.…”