A Randomized, Double-Blinded, Placebo-Controlled, Phase 1 Study of a Replication-Defective Herpes Simplex Virus (HSV) Type 2 Vaccine, HSV529, in Adults With or Without HSV Infection

Q2 · MEDICINE

Article

Author: Dropulic, Lesia K ; Smith, Malisa T ; Oestreich, Makinna C ; Hunsberger, Sally ; Phogat, Sanjay ; Pietz, Harlan L ; Wang, Kening ; Lumbard, Keith ; Turk, Siu Ping ; Koelle, David M ; Hornung, Ronald L ; Laing, Kerry J ; Hosken, Nancy A ; Chen, Aiying ; Cohen, Jeffrey I ; Garabedian, Doreen ; Chang, Lee-Jah ; Seshadri, Chetan

AbstractBackgroundHerpes simplex virus 2 (HSV2) causes genital herpes in >400 million persons worldwide.MethodsWe conducted a randomized, double-blinded, placebo-controlled trial of a replication-defective HSV2 vaccine, HSV529. Twenty adults were enrolled in each of 3 serogroups of individuals: those negative for both HSV1 and HSV2 (HSV1−/HSV2−), those positive or negative for HSV1 and positive for HSV2 (HSV1±/HSV2+), and those positive for HSV1 and negative for HSV2 (HSV1+/HSV2−). Sixty participants received vaccine or placebo at 0, 1, and 6 months. The primary end point was the frequency of solicited local and systemic reactions to vaccination.ResultsEighty-nine percent of vaccinees experienced mild-to-moderate solicited injection site reactions, compared with 47% of placebo recipients (95% confidence interval [CI], 12.9%–67.6%; P = .006). Sixty-four percent of vaccinees experienced systemic reactions, compared with 53% of placebo recipients (95% CI, −17.9% to 40.2%; P = .44). Seventy-eight percent of HSV1−/HSV2− vaccine recipients had a ≥4-fold increase in neutralizing antibody titer after 3 doses of vaccine, whereas none of the participants in the other serogroups had such responses. HSV2-specific CD4+ T-cell responses were detected in 36%, 46%, and 27% of HSV1−/HSV2−, HSV1±/HSV2+, and HSV1+/HSV2− participants, respectively, 1 month after the third dose of vaccine, and CD8+ T-cell responses were detected in 14%, 8%, and 18% of participants, respectively.ConclusionsHSV529 vaccine was safe and elicited neutralizing antibody and modest CD4+ T-cell responses in HSV-seronegative vaccinees.Clinical Trials RegistrationNCT01915212.

01 Feb 2009·VaccineQ3 · MEDICINE

Population-level effect of potential HSV2 prophylactic vaccines on HIV incidence in sub-Saharan Africa

Q3 · MEDICINE

Article

Author: Roel Bakker ; Richard G. White ; Anne Buvé ; Richard J. Hayes ; Kate K. Orroth ; Esther E. Freeman ; Judith R. Glynn ; Helen A. Weiss

Herpes simplex virus type-2 (HSV2) infection increases HIV transmission. We explore the impact of a potential prophylactic HSV2 vaccination on HIV incidence in Africa using STDSIM an individual-based model. A campaign that achieved 70% coverage over 5 years with a vaccine that reduced susceptibility to HSV2 acquisition and HSV2 reactivation by 75% for 10 years, reduced HIV incidence by 30-40% after 20 years (range 4-66%). Over 20 years, in most scenarios fewer than 100 vaccinations were required to avert one HIV infection. HSV2 vaccines could have a substantial impact on HIV incidence. Intensified efforts are needed to develop an effective HSV2 vaccine.

eLife

Sex and prior exposure jointly shape innate immune responses to a live herpesvirus vaccine

Article

Author: Han, Kyu Lee ; Biancotto, Angelique ; Rachmaninoff, Nicholas ; Kotliarov, Yuri ; Apps, Richard ; Chen, Jinguo ; Cohen, Jeffrey I ; Candia, Julian ; Wang, Kening ; Cheung, Foo ; Tsang, John S ; Jordan, Tristan ; Pietz, Harlan ; Dropulic, Lesia ; Langweiler, Marc

Background:Both sex and prior exposure to pathogens are known to influence responses to immune challenges, but their combined effects are not well established in humans, particularly in early innate responses critical for shaping subsequent outcomes.Methods:We employed systems immunology approaches to study responses to a replication-defective, herpes simplex virus (HSV) 2 vaccine in men and women either naive or previously exposed to HSV.Results:Blood transcriptomic and cell population profiling showed substantial changes on day 1 after vaccination, but the responses depended on sex and whether the vaccinee was naive or previously exposed to HSV. The magnitude of early transcriptional responses was greatest in HSV naive women where type I interferon (IFN) signatures were prominent and associated negatively with vaccine-induced neutralizing antibody titers, suggesting that a strong early antiviral response reduced the uptake of this replication-defective virus vaccine. While HSV seronegative vaccine recipients had upregulation of gene sets in type I IFN (IFN-α/β) responses, HSV2 seropositive vaccine recipients tended to have responses focused more on type II IFN (IFN-γ) genes.Conclusions:These results together show that prior exposure and sex interact to shape early innate responses that then impact subsequent adaptive immune phenotypes.Funding:Intramural Research Program of the NIH, the National Institute of Allergy and Infectious Diseases, and other institutes supporting the Trans-NIH Center for Human Immunology, Autoimmunity, and Inflammation. The vaccine trial was supported through a clinical trial agreement between the National Institute of Allergy and Infectious Diseases and Sanofi Pasteur. Clinical trial number: NCT01915212.

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Indication	Highest Phase	Country/Location	Organization	Date
Herpes Simplex	Preclinical	IT	Vaxxit SRL	16 Mar 2022

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