Safety and immunogenicity of a modified-vaccinia-virus-Ankara-based influenza A H5N1 vaccine: a randomised, double-blind phase 1/2a clinical trial

Kreijtz, Joost H. C. M.; Goeijenbier, Marco; Moesker, Fleur M.; Dries, L. Van den; Goeijenbier, Simone; Gruyter, Heidi L.M. De; Lehmann, Michael H.; Mutsert, Gerrie de; Vijver, David van de; Volz, Asisa; Fouchier, Ron A. M.; Gorp, Eric C. M. Van; Rimmelzwaan, Guus F.; Sutter, Gerd; Osterhaus, Albert D. M. E.

doi:10.1016/s1473-3099(14)70963-6

Cited by 84 publications

(90 citation statements)

References 29 publications

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“…The breadth of the T cell response, as well as the structure of the T cell receptor (TCR), is important for the recognition of structurally similar epitopes, e.g., from viral variants which may prevent viral escape (5)(6)(7)(8). Several clinical trials of T cell inducing vaccines have been conducted not only for HCV and some ongoing approaches have shown promising T cell-inducing capacity (4,9,10). However, different vaccine receivers usually react to the vaccination with diverse T cell response magnitudes.…”

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confidence: 99%

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8⁺T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses

Zhang

Bakshi

Suneetha

et al. 2015

J Virol

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T cell responses play a critical role in controlling or clearing viruses. Therefore, strategies to prevent or treat infections include boosting T cell responses. T cells specific for various pathogens have been reported in unexposed individuals and an influence of such cells on the response toward vaccines is conceivable. However, little is known about their frequency, repertoire, and impact on vaccination. We performed a detailed characterization of CD8 ؉ T cells specific to a hepatitis C virus (HCV) epitope (NS3-1073) in 121 HCV-seronegative individuals. We show that in vitro HCV NS3-1073-specific CD8 ؉ T cell responses were rather abundantly detectable in one-third of HCV-seronegative individuals irrespective of risk factors for HCV exposure. Ex vivo, these NS3-1073-specific CD8 ؉ T cells were found to be both naive and memory cells. Importantly, recognition of various peptides derived from unrelated viruses by NS3-1073-specific CD8؉ T cells showed a considerable degree of T cell cross-reactivity, suggesting that they might in part originate from previous heterologous infections. Finally, we further provide evidence that preexisting NS3-1073-specific CD8 ؉ T cells can impact the T cell response toward peptide vaccination. Healthy, vaccinated individuals who showed an in vitro response toward NS3-1073 already before vaccination displayed a more vigorous and earlier response toward the vaccine. IMPORTANCE Preventive and therapeutic vaccines are being developed for many viral infections and often aim on inducing T cell responses.Despite effective antiviral drugs against HCV, there is still a need for a preventive vaccine. However, the responses to vaccines can be highly variable among different individuals. Preexisting T cells in unexposed individuals could be one reason that helps to explain the variable T cell responses to vaccines. Based on our findings, we suggest that HCV CD8 ؉ T cells are abundant in HCVseronegative individuals but that their repertoire is highly diverse due to the involvement of both naive precursors and crossreactive memory cells of different specificities, which can influence the response to vaccines. The data may emphasize the need to personalize immune-based therapies based on the individual's T cell repertoire that is present before the immune intervention.

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confidence: 99%

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8⁺T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses

Zhang

Bakshi

Suneetha

et al. 2015

J Virol

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“…MVA that drives the expression of NP and M1 protein was also tested in clinical trials and proved to be immunogenic in humans [64][65][66]. The MVA vector also has been used for the expression of HA and the induction of virus-neutralizing antibodies and has been evaluated as a candidate H5N1 vaccine in a phase 1/2 clinical trial [67][68][69][70][71].…”

Section: Vaccine Developmentmentioning

confidence: 99%

Universal influenza vaccines: a realistic option?

Vries

Altenburg

Rimmelzwaan

2016

Clinical Microbiology and Infection

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“…In contrast, although an inactivated H7N9(A/Shanghai/2/13) influenza vaccine mixed with MF59 adjuvant induced seroconversion in 59% of the clinically trialed adults aged 19-64 years old, its potential application might be limited by the absence of long-term antibody responses or clinical outcomes [111]. Apart from live attenuated and inactivated vaccines, viral vector-based influenza vaccines are tested in clinical trials and show immunogenicity in healthy adults [112, 113]. For example, a modified vaccinia virus Ankara (MVA)-HA-based H5N1 vaccine, MVA-H5-sfMR, induced antibody responses in young adults aged 18-28 year old, with a single dose of higher virus titer resulting in stronger responses than did two immunizations with a lower virus dose.…”

Section: Clinically Trialed and Licensed Influenza Vaccinesmentioning

confidence: 99%

Advancements in the development of subunit influenza vaccines

Zhang

Zheng

et al. 2015

Microbes and Infection

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The ongoing threat of influenza epidemics and pandemics has emphasized the importance of developing safe and effective vaccines against infections from divergent influenza viruses. In this review, we first introduce the structure and life cycle of influenza A viruses, describing major influenza A virus-caused pandemics. We then compare different types of influenza vaccines and discuss current advancements in the development of subunit influenza vaccines, particularly those based on nucleoprotein (NP), extracellular domain of matrix protein 2 (M2e) and hemagglutinin (HA) proteins. We also illustrate potential strategies for improving the efficacy of subunit influenza vaccines.

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Safety and immunogenicity of a modified-vaccinia-virus-Ankara-based influenza A H5N1 vaccine: a randomised, double-blind phase 1/2a clinical trial

Cited by 84 publications

References 29 publications

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8⁺T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8⁺T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses

Universal influenza vaccines: a realistic option?

Advancements in the development of subunit influenza vaccines

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Safety and immunogenicity of a modified-vaccinia-virus-Ankara-based influenza A H5N1 vaccine: a randomised, double-blind phase 1/2a clinical trial

Cited by 84 publications

References 29 publications

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8+T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8+T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses

Universal influenza vaccines: a realistic option?

Advancements in the development of subunit influenza vaccines

Contact Info

Product

Resources

About

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8⁺T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses

Frequency, Private Specificity, and Cross-Reactivity of Preexisting Hepatitis C Virus (HCV)-Specific CD8⁺T Cells in HCV-Seronegative Individuals: Implications for Vaccine Responses