Frequent Recurrences of Genital Herpes Are Associated with Enhanced Systemic HSV-Specific T Cell Response

Holub, Michal; Stráníková, Alžběta; Chalupa, Pavel; Arientová, Simona; Roubalová, K; Beran, Ondřej

doi:10.1155/2020/5640960

Cited by 1 publication

(1 citation statement)

References 24 publications

(27 reference statements)

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“…These approaches will likely demonstrate varied efficacy in clinical trials; although, they have demonstrated high efficacy in preclinical animal models. It is important to note that there were reports that an exacerbated CD8+T cell response through repeated reactivation may increase the rate of reactivation [ 87 ]. Therefore, an effective vaccine approach is required to protect without exacerbating the reactivation of the latent virus, suggesting that both inflammatory and immune-regulatory pathways and cellular milieus must be considered.…”

Section: Clinical Trials Of Herpes Simplex Vaccinesmentioning

confidence: 99%

Rational Design of Live-Attenuated Vaccines against Herpes Simplex Viruses

Stanfield

Kousoulas

Fernández³

et al. 2021

Viruses

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Diseases caused by human herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) affect millions of people worldwide and range from fatal encephalitis in neonates and herpes keratitis to orofacial and genital herpes, among other manifestations. The viruses can be shed efficiently by asymptomatic carriers, causing increased rates of infection. Viral transmission occurs through direct contact of mucosal surfaces followed by initial replication of the incoming virus in skin tissues. Subsequently, the viruses infect sensory neurons in the trigeminal and lumbosacral dorsal root ganglia, where they are primarily maintained in a transcriptionally repressed state termed “latency”, which persists for the lifetime of the host. HSV DNA has also been detected in other sympathetic ganglia. Periodically, latent viruses can reactivate, causing ulcerative and often painful lesions primarily at the site of primary infection and proximal sites. In the United States, recurrent genital herpes alone accounts for more than a billion dollars in direct medical costs per year, while there are much higher costs associated with the socio-economic aspects of diseased patients, such as loss of productivity due to mental anguish. Currently, there are no effective FDA-approved vaccines for either prophylactic or therapeutic treatment of human herpes simplex infections, while several recent clinical trials have failed to achieve their endpoint goals. Historically, live-attenuated vaccines have successfully combated viral diseases, including polio, influenza, measles, and smallpox. Vaccines aimed to protect against the devastation of smallpox led to the most significant achievement in medical history: the eradication of human disease by vaccination. Recently, novel approaches toward developing safe and effective live-attenuated vaccines have demonstrated high efficacy in various preclinical models of herpetic disease. This next generation of live-attenuated vaccines has been tailored to minimize vaccine-associated side effects and promote effective and long-lasting immune responses. The ultimate goal is to prevent or reduce primary infections (prophylactic vaccines) or reduce the frequency and severity of disease associated with reactivation events (therapeutic vaccines). These vaccines’ “rational” design is based on our current understanding of the immunopathogenesis of herpesviral infections that guide the development of vaccines that generate robust and protective immune responses. This review covers recent advances in the development of herpes simplex vaccines and the current state of ongoing clinical trials in pursuit of an effective vaccine against herpes simplex virus infections and associated diseases.

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Section: Clinical Trials Of Herpes Simplex Vaccinesmentioning

confidence: 99%