Preliminary Assessment of the Efficacy of a T-Cell–Based Influenza Vaccine, MVA-NP+M1, in Humans

Lillie, Patrick; Berthoud, Tamara; Powell, Timothy J.; Lambe, Teresa; Mullarkey, Caitlin E.; Spencer, Alexandra J.; Hamill, Matthew M; Peng, Yanchun; Blais, Marie Eve; Duncan, Christopher; Sheehy, Suzanne; Havelock, Tom; Faust, Saul N.; Williams, R; Gilbert, Anthony; Oxford, John; Dong, Tao; Hill, Adrian V. S.; Gilbert, Sarah C.

doi:10.1093/cid/cis327

Cited by 229 publications

(225 citation statements)

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“…First, we recognize that it is difficult to separate the roles of ADCC and T cells in controlling H1N1pdm replication, although recent experiments with humans suggest a limited role for T cell immunity (53). Future experiments using passive antibody transfer, adoptive T cell transfer, and antibody- mediated depletion of lymphocyte subsets will help to delineate the distinct roles of these cells in mediating cross-protection.…”

Section: Discussionmentioning

confidence: 99%

Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques

Jegaskanda

Weinfurter

Friedrich

et al. 2013

J Virol

171

169

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Furthermore, we found that influenza virus-specific ADCC was present in bronchoalveolar lavage fluid and was able to activate lung NK cells. We concluded that infection with a seasonal influenza virus can induce antibodies that mediate ADCC capable of recognizing divergent influenza virus strains. Cross-reactive ADCC may provide a mechanism for reducing the severity of divergent influenza virus infections.

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Section: Discussionmentioning

confidence: 99%

Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques

Jegaskanda

Weinfurter

Friedrich

et al. 2013

J Virol

171

169

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“…Several candidate universal influenza vaccines are in various stages of development (29,34,(53)(54)(55)(56). Those that aim at the induction of cross-protective T cell responses especially hold promise, as it has been shown in numerous animal models that the induction of virus-specific T cell responses affords protection against challenge infection (12,57).…”

Section: Discussionmentioning

confidence: 99%

Infection of the Upper Respiratory Tract with Seasonal Influenza A(H3N2) Virus Induces Protective Immunity in Ferrets against Infection with A(H1N1)pdm09 Virus after Intranasal, but Not Intratracheal, Inoculation

Bodewes

Kreijtz

Amerongen

et al. 2013

J Virol

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“…IIa vaccination and influenza challenge study, MVA-NP+M1 additionally demonstrated clinical efficacy in healthy adult volunteers [10]. A coadministration regimen could have the advantage of simultaneously inducing cell-mediated and humoral immunity.…”

Section: Indicated That Preexisting Cd4mentioning

confidence: 96%

Improved adjuvanting of seasonal influenza vaccines: Preclinical studies of MVA‐NP+M1 coadministration with inactivated influenza vaccine

et al. 2013

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Licensed seasonal influenza vaccines induce antibody (Ab) responses against influenza hemagglutinin (HA) that are limited in their ability to protect against different strains of influenza. Cytotoxic T lymphocytes recognizing the conserved internal nucleoprotein (NP) and matrix protein (M1) are capable of mediating a cross-subtype immune response against influenza. Modified vaccinia Ankara (MVA) virus encoding NP and M1(MVA-NP+M1) is designed to boost preexisting T-cell responses in adults in order to elicit a cross-protective immune response. We examined the coadministration of HA protein formulations and candidate MVA-NP+M1 influenza vaccines in murine, avian, and swine models. Ab responses postimmunization were measured by ELISA and pseudotype neutralization assays. Here, we demonstrate that MVA-NP+M1 can act as an adjuvant enhancing Ab responses to HA while simultaneously inducing potent T-cell responses to conserved internal Ags. We show that this regimen leads to the induction of cytophilic Ab isotypes that are capable of inhibiting hemagglutination and in the context of H5 exhibit cross-clade neutralization. The simultaneous induction of T cells and Ab responses has the potential to improve seasonal vaccine performance and could be employed in pandemic situations. Keywords: Adjuvants r Influenza vaccines r T cells r VaccinationAdditional supporting information may be found in the online version of this article at the publisher's web-site IntroductionFor the past 60 years, vaccination has and continues to be the main method to combat both seasonal and pandemic influenza. While Correspondence: Caitlin E. Mullarkey e-mail: caitlin.mullarkey@ndm.ox.ac.uk the strains included in seasonal influenza vaccines are updated regularly, in over half a century there have been few changes in the overall vaccination strategy. It is well established that licensed influenza vaccines work by eliciting neutralizing antibodies against the surface hemagglutinin (HA) protein, yet these antibodies confer little or no protection against distinct subtypes [1]. Subsequently, the efficacy of existing vaccines is highly dependent on correctly matching vaccine strains with circulating influenza C 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2013. 43: 1940-1952 Clinical immunology 1941 strains [2]. Protection rates vary year to year and are estimated in healthy adults to be between 60 and 90% when the strains are correctly matched [3]. However, a recent meta-analysis assessing the efficacy and effectiveness of seasonal influenza vaccines suggests that protection rates may be overestimated [4]. Moreover, protection rates in the elderly are even lower despite the fact that this demographic accounts for 90% of influenza-related mortality and is a key target in vaccination campaigns [4]. There is a vital need to develop more effective influenza vaccines and to reevaluate influenza vaccination strategies especially with regard to pandemic preparedness. "Universal flu vaccines" that elicit cross-protect...

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Preliminary Assessment of the Efficacy of a T-Cell–Based Influenza Vaccine, MVA-NP+M1, in Humans

Abstract: A single vaccination with MVA-NP+M1 boosts T-cell responses to conserved influenza antigens in humans. Protection against influenza disease and virus shedding was demonstrated in an influenza virus challenge study.

Cited by 229 publications

References 14 publications

Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques

Antibody-Dependent Cellular Cytotoxicity Is Associated with Control of Pandemic H1N1 Influenza Virus Infection of Macaques

Infection of the Upper Respiratory Tract with Seasonal Influenza A(H3N2) Virus Induces Protective Immunity in Ferrets against Infection with A(H1N1)pdm09 Virus after Intranasal, but Not Intratracheal, Inoculation

Improved adjuvanting of seasonal influenza vaccines: Preclinical studies of MVA‐NP+M1 coadministration with inactivated influenza vaccine

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