Immune responses to a HSV-2 polynucleotide immunotherapy COR-1 in HSV-2 positive subjects: A randomized double blinded phase I/IIa trial


Autoři: Janin Chandra aff001;  Wai-Ping Woo aff001;  Julie L. Dutton aff001;  Yan Xu aff001;  Bo Li aff001;  Sally Kinrade aff003;  Julian Druce aff004;  Neil Finlayson aff001;  Paul Griffin aff006;  Kerry J. Laing aff010;  David M. Koelle aff010;  Ian H. Frazer aff001
Působiště autorů: Admedus Vaccines Pty Ltd (formerly Coridon Pty Ltd), Translational Research Institute, Woolloongabba, Queensland, Australia aff001;  University of Queensland, Diamantina Institute, Translational Research Institute, Woolloongabba, Queensland, Australia aff002;  Medicines Development Limited, Southbank, Victoria, Australia aff003;  Victorian Infectious Diseases Reference Laboratory, Melbourne, Victoria, Australia aff004;  Doherty Institute, Melbourne, Victoria, Australia aff005;  Q-Pharm Pty Ltd, Brisbane, Queensland, Australia aff006;  Department of Medicine and Infectious Diseases, Mater Hospital and Mater Medical Research Institute, Brisbane, Queensland, Australia aff007;  The University of Queensland, Brisbane, Queensland, Australia aff008;  QIMR Berghofer, Clinical Tropical Medicine Lab, Brisbane, Queensland, Australia aff009;  Department of Medicine, University of Washington, Seattle, Washington, United States of America aff010;  Department of Laboratory Medicine, University of Washington, Seattle, Washington, United States of America aff011;  Vaccine and Infectious Diseases Division, Fred Hutchinson Cancer Research Institute, Seattle, Washington, United States of America aff012;  Department of Global Health, University of Washington, Seattle, Washington, United states of America aff013;  Benaroya Research Institute, Seattle, Washington, United States of America aff014
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226320

Souhrn

Background

Genital herpes simplex infection affects more than 500 million people worldwide. We have previously shown that COR-1, a therapeutic HSV-2 polynucleotide vaccine candidate, is safe and well tolerated in healthy subjects.

Objective

Here, we present a single center double-blind placebo-controlled, randomized phase I/IIa trial of COR-1 in HSV-2 positive subjects in which we assessed safety and tolerability as primary endpoints, and immunogenicity and therapeutic efficacy as exploratory endpoints.

Methods

Forty-four HSV-2+ subjects confirmed by positive serology or pathology, and positive qPCR during baseline shedding, with a recurrent genital HSV-2 history of at least 12 months including three to nine reported lesions in 12 months prior to screening, aged 18 to 50 years females and males with given written informed consent, were randomized into two groups. Three immunizations at 4-week intervals and one booster immunization at 6 months, each of 1 mg COR-1 DNA or placebo, were administered intradermally as two injections of 500 μg each to either one forearm or both forearms.

Results

No serious adverse events, life-threatening events or deaths occurred throughout the study. As expected, HSV-2 infected subjects displayed gD2-specific antibody titers prior to immunization. COR-1 was associated with a reduction in viral shedding after booster administration compared with baseline.

Conclusions

This study confirms the previously demonstrated safety of COR-1 in humans and indicates a potential for use of COR-1 as a therapy to reduce viral shedding in HSV-2 infected subjects.

Klíčová slova:

Antibodies – Antigens – Enzyme-linked immunoassays – Immune response – T cells – Vaccines – Viral release


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2019 Číslo 12