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A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans.
Clin Vaccine Immunol. 2015 Jul; 22(7):828-35.CV

Abstract

Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n = 16) or FLU-v (500 μg) and the adjuvant (n = 16), both in saline. Twenty-one days later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average ± the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold ± 0.2-fold and 1.6-fold ± 0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold ± 3.9-fold versus 1.3-fold ± 0.1-fold higher than the negative-control value [average ± SEM] for FLU-v versus the placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads. (This study has been registered at ClinicalTrials.gov under registration no. NCT01226758 and at hra.nhs.uk under EudraCT no. 2009-014716-35.).

Authors+Show Affiliations

SEEK, Central Point, London, United Kingdom.SEEK, Central Point, London, United Kingdom.SEEK, Central Point, London, United Kingdom.SEEK, Central Point, London, United Kingdom.Retroscreen Virology Ltd., Queen Mary BioEnterprises, Innovation Centre, London, United Kingdom.Retroscreen Virology Ltd., Queen Mary BioEnterprises, Innovation Centre, London, United Kingdom.Retroscreen Virology Ltd., Queen Mary BioEnterprises, Innovation Centre, London, United Kingdom.Clinical Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.Retroscreen Virology Ltd., Queen Mary BioEnterprises, Innovation Centre, London, United Kingdom.Retroscreen Virology Ltd., Queen Mary BioEnterprises, Innovation Centre, London, United Kingdom Blizzard Institute, Queen Mary College, University of London, London, United Kingdom.SEEK, Central Point, London, United Kingdom wilson.wanderley@seekacure.com.

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25994549

Citation

Pleguezuelos, Olga, et al. "A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates With Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans." Clinical and Vaccine Immunology : CVI, vol. 22, no. 7, 2015, pp. 828-35.
Pleguezuelos O, Robinson S, Fernández A, et al. A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans. Clin Vaccine Immunol. 2015;22(7):828-35.
Pleguezuelos, O., Robinson, S., Fernández, A., Stoloff, G. A., Mann, A., Gilbert, A., Balaratnam, G., Wilkinson, T., Lambkin-Williams, R., Oxford, J., & Caparrós-Wanderley, W. (2015). A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans. Clinical and Vaccine Immunology : CVI, 22(7), 828-35. https://doi.org/10.1128/CVI.00098-15
Pleguezuelos O, et al. A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates With Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans. Clin Vaccine Immunol. 2015;22(7):828-35. PubMed PMID: 25994549.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A Synthetic Influenza Virus Vaccine Induces a Cellular Immune Response That Correlates with Reduction in Symptomatology and Virus Shedding in a Randomized Phase Ib Live-Virus Challenge in Humans. AU - Pleguezuelos,Olga, AU - Robinson,Stuart, AU - Fernández,Ana, AU - Stoloff,Gregory A, AU - Mann,Alex, AU - Gilbert,Anthony, AU - Balaratnam,Ganesh, AU - Wilkinson,Tom, AU - Lambkin-Williams,Rob, AU - Oxford,John, AU - Caparrós-Wanderley,Wilson, Y1 - 2015/05/20/ PY - 2015/02/23/received PY - 2015/05/13/accepted PY - 2015/5/22/entrez PY - 2015/5/23/pubmed PY - 2016/3/16/medline SP - 828 EP - 35 JF - Clinical and vaccine immunology : CVI JO - Clin Vaccine Immunol VL - 22 IS - 7 N2 - Current influenza vaccines elicit primarily antibody-based immunity. They require yearly revaccination and cannot be manufactured until the identification of the circulating viral strain(s). These issues remain to be addressed. Here we report a phase Ib trial of a vaccine candidate (FLU-v) eliciting cellular immunity. Thirty-two males seronegative for the challenge virus by hemagglutination inhibition assay participated in this single-center, randomized, double-blind study. Volunteers received one dose of either the adjuvant alone (placebo, n = 16) or FLU-v (500 μg) and the adjuvant (n = 16), both in saline. Twenty-one days later, FLU-v (n = 15) and placebo (n = 13) volunteers were challenged with influenza virus A/Wisconsin/67/2005 (H3N2) and monitored for 7 days. Safety, tolerability, and cellular responses were assessed pre- and postvaccination. Virus shedding and clinical signs were assessed postchallenge. FLU-v was safe and well tolerated. No difference in the prevaccination FLU-v-specific gamma interferon (IFN-γ) response was seen between groups (average ± the standard error of the mean [SEM] for the placebo and FLU-v, respectively, 1.4-fold ± 0.2-fold and 1.6-fold ± 0.5-fold higher than the negative-control value). Nineteen days postvaccination, the FLU-v group, but not the placebo group, developed FLU-v-specific IFN-γ responses (8.2-fold ± 3.9-fold versus 1.3-fold ± 0.1-fold higher than the negative-control value [average ± SEM] for FLU-v versus the placebo [P = 0.0005]). FLU-v-specific cellular responses also correlated with reductions in both viral titers (P = 0.01) and symptom scores (P = 0.02) postchallenge. Increased cellular immunity specific to FLU-v correlates with reductions in both symptom scores and virus loads. (This study has been registered at ClinicalTrials.gov under registration no. NCT01226758 and at hra.nhs.uk under EudraCT no. 2009-014716-35.). SN - 1556-679X UR - https://www.unboundmedicine.com/medline/citation/25994549/A_Synthetic_Influenza_Virus_Vaccine_Induces_a_Cellular_Immune_Response_That_Correlates_with_Reduction_in_Symptomatology_and_Virus_Shedding_in_a_Randomized_Phase_Ib_Live_Virus_Challenge_in_Humans_ DB - PRIME DP - Unbound Medicine ER -