Adjuvanted or whole-virion vaccine for 2009 influenza A (H1N1)

[tetano]

The Lancet Infectious Diseases, Volume 11, Issue 7, Pages 497 - 498, July 2011

doi:10.1016/S1473-3099(11)70156-6Cite or Link Using DOI
Adjuvanted or whole-virion vaccine for 2009 influenza A (H1N1) ? Authors' reply
Katja Hoschler a, Maria Zambon a, Karl G Nicholson bEmail Address
We recognise that the sensitivity of the haemagglutination-inhibition assay is crucial to manufacturers. We were careful to avoid issues of assay technical performance that might produce specious differences in the serum analysis in our study.1 The laboratory was masked to vaccine allocation and analysed all serum samples with identical protocols. Samples from each patient were assayed together, and masked serological data were released to an independent statistician holding the randomisation codes. We included the International Serum Standard for H1N1 2009 (09/194) in all human H1N1 vaccine studies and obtained consistent antibody titres, which were well within two SD of mean attributed values on each occasion the standard was assayed and provides another measure of consistency and quality assurance. We routinely use virus propagated in embryonated chicken eggs for serological analyses, and analysed both vaccines with the same virus preparation. We did not record that use of cell-culture-derived H1N1 antigen resulted in higher titres when measuring responses against a cell-culture-derived vaccine in a previous study.2
The immunogenicity of the whole-virion vaccine was consistently lower than that of the adjuvanted vaccine, as measured by both haemagglutination-inhibition and microneutralisation assays.3 Recipients of the adjuvanted vaccine met more Committee for Medicinal Products for Human Use (CHMP) criteria more rapidly than did recipients of the whole-virion vaccine. Our antibody findings accord with those of another direct comparison of the same vaccines in children,4 which were also analysed masked in our laboratory. The results are supported by a study in ferrets,5 in which the serology was undertaken in other laboratories. In ferrets, whole-virion vaccine was less immunogenic than was adjuvanted vaccine by haemagglutination inhibition, and the serology correlated with protection against virus challenge.5 We maintain that data and conclusions about relative immunogenicity from the direct comparative studies are robust, and that there is no evidence that the laboratory methodology brings about these analytical outcomes.

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[tetano]

Re: Adjuvanted or whole-virion vaccine for 2009 influenza A (H1N1)

The Lancet Infectious Diseases, Volume 11, Issue 7, Pages 496 - 497, July 2011

doi:10.1016/S1473-3099(11)70155-4Cite or Link Using DOI
Adjuvanted or whole-virion vaccine for 2009 influenza A (H1N1)
P Noel Barrett aEmail Address, Hartmut J Ehrlich b
In a study of the comparative safety and immunogenicity of two 2009 pandemic influenza A (H1N1) vaccines, Karl Nicholson and colleagues1 reported that an adjuvanted vaccine induced a more robust immune response than did a non-adjuvanted, whole-virion vaccine. However, much of the reported data differ from results of our studies with the non-adjuvanted vaccine; we recorded substantially higher levels of seroprotection in all age groups, even at a lower 3?75 μg dose (table). This discrepancy might be explained by low sensitivity of the haemagglutination-inhibition assay used by Nicholson and colleagues; who reported only 13% seropositivity at baseline in all participants. Another UK-based study, undertaken by Miller and colleagues,2 reported baseline seropositivity of 36?6% in patients in a similar age group (≥15 years). This discrepancy is also pronounced in elderly people (>65 years), with baseline seroprotection rates of 5?6% and 23?3% reported by Nicholson and colleagues and Miller and colleagues, respectively. The low baseline seroprotection rates, especially in elderly individuals, contrast with those recorded by several other seroepidemiological and vaccine studies,3, 4 which are similar to our data (table). These reports suggest that the haemagglutination-inhibition assay used by Nicholson and colleagues might underestimate the level of seroprotection induced by the whole-virion vaccine.

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