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Your search keyword '"Phyllis Renehan"' showing total 2 results
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2 results on '"Phyllis Renehan"'

1. DNA priming for seasonal influenza vaccine: a phase 1b double-blind randomized clinical trial.

Author

Julie E Ledgerwood, Abbie R Bellamy, Robert Belshe, David I Bernstein, Srilatha Edupuganti, Shital M Patel, Phyllis Renehan, Thad Zajdowicz, Richard Schwartz, Richard Koup, Robert T Bailer, Galina V Yamshchikov, Mary E Enama, Uzma Sarwar, Brenda Larkin, Barney S Graham, and VRC 701 study team

Subjects
Medicine, Science
Abstract

The efficacy of current influenza vaccines is limited in vulnerable populations. DNA vaccines can be produced rapidly, and may offer a potential strategy to improve vaccine immunogenicity, indicated by studies with H5 influenza DNA vaccine prime followed by inactivated vaccine boost.Four sites enrolled healthy adults, randomized to receive 2011/12 seasonal influenza DNA vaccine prime (n=65) or phosphate buffered saline (PBS) (n=66) administered intramuscularly with Biojector. All subjects received the 2012/13 seasonal inactivated influenza vaccine, trivalent (IIV3) 36 weeks after the priming injection. Vaccine safety and tolerability was the primary objective and measurement of antibody response by hemagglutination inhibition (HAI) was the secondary objective.The DNA vaccine prime-IIV3 boost regimen was safe and well tolerated. Significant differences in HAI responses between the DNA vaccine prime and the PBS prime groups were not detected in this study.While DNA priming significantly improved the response to a conventional monovalent H5 vaccine in a previous study, it was not effective in adults using seasonal influenza strains, possibly due to pre-existing immunity to the prime, unmatched prime and boost antigens, or the lengthy 36 week boost interval. Careful optimization of the DNA prime-IIV3 boost regimen as related to antigen matching, interval between vaccinations, and pre-existing immune responses to influenza is likely to be needed in further evaluations of this vaccine strategy. In particular, testing this concept in younger age groups with less prior exposure to seasonal influenza strains may be informative.ClinicalTrials.gov NCT01498718.

Published
2015
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2. Safety and tolerability of chikungunya virus-like particle vaccine in healthy adults: a phase 1 dose-escalation trial

Author

Lee-Jah, Chang, Kimberly A, Dowd, Floreliz H, Mendoza, Jamie G, Saunders, Sandra, Sitar, Sarah H, Plummer, Galina, Yamshchikov, Uzma N, Sarwar, Zonghui, Hu, Mary E, Enama, Robert T, Bailer, Richard A, Koup, Richard M, Schwartz, Wataru, Akahata, Gary J, Nabel, John R, Mascola, Theodore C, Pierson, Barney S, Graham, Julie E, Ledgerwood, and Phyllis, Renehan

Subjects
Adult, Male, medicine.medical_specialty, Allergy, Adolescent, Enzyme-Linked Immunosorbent Assay, medicine.disease_cause, Internal medicine, Commentaries, medicine, Immune Tolerance, Humans, Chikungunya, Adverse effect, biology, business.industry, Immunogenicity, Vaccination, Viral Vaccines, General Medicine, Middle Aged, medicine.disease, Antibodies, Neutralizing, Clinical trial, Tolerability, Immunology, biology.protein, Female, Antibody, business, Chikungunya virus
Abstract

Chikungunya virus--a mosquito-borne alphavirus--is endemic in Africa and south and southeast Asia and has recently emerged in the Caribbean. No drugs or vaccines are available for treatment or prevention. We aimed to assess the safety, tolerability, and immunogenicity of a new candidate vaccine.VRC 311 was a phase 1, dose-escalation, open-label clinical trial of a virus-like particle (VLP) chikungunya virus vaccine, VRC-CHKVLP059-00-VP, in healthy adults aged 18-50 years who were enrolled at the National Institutes of Health Clinical Center (Bethesda, MD, USA). Participants were assigned to sequential dose level groups to receive vaccinations at 10 μg, 20 μg, or 40 μg on weeks 0, 4, and 20, with follow-up for 44 weeks after enrolment. The primary endpoints were safety and tolerability of the vaccine. Secondary endpoints were chikungunya virus-specific immune responses assessed by ELISA and neutralising antibody assays. This trial is registered with ClinicalTrials.gov, NCT01489358.25 participants were enrolled from Dec 12, 2011, to March 22, 2012, into the three dosage groups: 10 μg (n=5), 20 μg (n=10), and 40 μg (n=10). The protocol was completed by all five participants at the 10 μg dose, all ten participants at the 20 μg dose, and eight of ten participants at the 40 μg dose; non-completions were for personal circumstances unrelated to adverse events. 73 vaccinations were administered. All injections were well tolerated, with no serious adverse events reported. Neutralising antibodies were detected in all dose groups after the second vaccination (geometric mean titres of the half maximum inhibitory concentration: 2688 in the 10 μg group, 1775 in the 20 μg group, and 7246 in the 40 μg group), and a significant boost occurred after the third vaccination in all dose groups (10 μg group p=0·0197, 20 μg group p0·0001, and 40 μg group p0·0001). 4 weeks after the third vaccination, the geometric mean titres of the half maximum inhibitory concentration were 8745 for the 10 μg group, 4525 for the 20 μg group, and 5390 for the 40 μg group.The chikungunya VLP vaccine was immunogenic, safe, and well tolerated. This study represents an important step in vaccine development to combat this rapidly emerging pathogen. Further studies should be done in a larger number of participants and in more diverse populations.Intramural Research Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, and National Institutes of Health.

Published
2014

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