2008
DOI: 10.1371/journal.ppat.1000138
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Superior Immunogenicity of Inactivated Whole Virus H5N1 Influenza Vaccine is Primarily Controlled by Toll-like Receptor Signalling

Abstract: In the case of an influenza pandemic, the current global influenza vaccine production capacity will be unable to meet the demand for billions of vaccine doses. The ongoing threat of an H5N1 pandemic therefore urges the development of highly immunogenic, dose-sparing vaccine formulations. In unprimed individuals, inactivated whole virus (WIV) vaccines are more immunogenic and induce protective antibody responses at a lower antigen dose than other formulations like split virus (SV) or subunit (SU) vaccines. The … Show more

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Cited by 221 publications
(205 citation statements)
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“…This is in accordance with our previous findings that removal of RNA in the VLPs leads to a shift from the IgG2a to the IgG1 isotype [33,34,37]. Importantly, in the publication of Geeraedts et al [36], hemagglutination inhibition (HI) titers follow a similar pattern as total IgG titers in spite of a shift in isotype suggesting that the protective potential of the immune response in this case is dependent of the magnitude of the immune response rather than the isotypes induced. This corresponds to the fact that M2 antibody operates through ADCC while HI antibodies are truly neutralizing.…”
Section: Inducing Protective M2e Antibodies By Vaccination: Tlr-signasupporting
confidence: 92%
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“…This is in accordance with our previous findings that removal of RNA in the VLPs leads to a shift from the IgG2a to the IgG1 isotype [33,34,37]. Importantly, in the publication of Geeraedts et al [36], hemagglutination inhibition (HI) titers follow a similar pattern as total IgG titers in spite of a shift in isotype suggesting that the protective potential of the immune response in this case is dependent of the magnitude of the immune response rather than the isotypes induced. This corresponds to the fact that M2 antibody operates through ADCC while HI antibodies are truly neutralizing.…”
Section: Inducing Protective M2e Antibodies By Vaccination: Tlr-signasupporting
confidence: 92%
“…Taken together, these results show that TLR7 -/-mice can be protected by an antibody of the right isotype, suggesting that the failure of the vaccine to protect TLR7 -/-mice is not due to an intrinsic higher susceptibility of the mice, but rather due to the induction of IgG1 instead of IgG2a. Likewise, the importance of TLR signaling in mediating protection from influenza infection has also been reported for classical HA-based vaccines [35,36]. In fact, Geeraedts et al [36] in an elegant study could show that the improved protection observed for whole inactivated viruses (WIVs) compared with subunit or split virus could be attributed to the RNA contained in the WIV vaccine.…”
mentioning
confidence: 88%
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“…Nevertheless, recent studies have shown that TLR's role in regulating the adaptive responses can be harnessed to boost immunogenicity of influenza vaccines (e.g., TLR9 or TLR7 ligands as adjuvants). This may be particularly useful in the elderly and the immunologically naïve vaccinees 4, 33, 34, 35, 36, 37, 38, 39, 40. Our data in natural influenza provide additional support to this new vaccination approach.…”
Section: Discussionmentioning
confidence: 65%
“…Ein Ganzvirusimpfstoff weist im Vergleich zu Spalt-und Untereinheitenimpfstoffen, die auf einem hochreinen Antigengehalt basieren, eine höhere Immunogenität auf, was auf das Vorhandensein interner Virusproteine, zellulärer Lipide der Virushülle und die im Viruspartikel enthaltenen Einzelstrang-RNA zurück-geführt wird [26]. Von Letzterer wurde gezeigt, dass sie als "pathogen-associated molecular pattern" (PAMP) durch den Toll like receptor 7 (TLR7) erkannt wird, was zu einer verstärkten Aktivierung des angeborenen Immunsystems führt [27]. Eine Zugabe von Adjuvans wird bei den meisten verfügbaren TIV-Impfstoffen nicht vorgenommen; dies könnte zwar das Erreichen der oben genannten Ziele (Boosterung und Verbreiterung der vorbestehenden Immunität) positiv beeinflussen, müsste aber mit einer schlechteren lokalen Verträglichkeit erkauft werden [28].…”
Section: Introductionunclassified