scholarly journals Assessment of Two Novel Live-Attenuated Vaccine Candidates for Herpes Simplex Virus 2 (HSV-2) in Guinea Pigs

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 258
Author(s):  
Jonathan D. Joyce ◽  
Anant K. Patel ◽  
Brandie Murphy ◽  
Daniel J.J. Carr ◽  
Edward Gershburg ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Guinea Pigs ◽  
Dorsal Root ◽  
Vaccine Candidate ◽  
Sympathetic Ganglia ◽  
Vaccine Candidates ◽  
Vaginal Secretions ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

Treatment to ameliorate the symptoms of infection with herpes simplex virus 2 (HSV-2) and to suppress reactivation has been available for decades. However, a safe and effective preventative or therapeutic vaccine has eluded development. Two novel live-attenuated HSV-2 vaccine candidates (RVx201 and RVx202) have been tested preclinically for safety. Hartley guinea pigs were inoculated vaginally (n = 3) or intradermally (n = 16) with either vaccine candidate (2 × 107 PFU) and observed for disease for 28 days. All animals survived to study end without developing HSV-2-associated disease. Neither vaccine candidate established latency in dorsal root or sacral sympathetic ganglia, as determined by viral DNA quantification, LAT expression, or explant reactivation. Infectious virus was shed in vaginal secretions for three days following vaginal inoculation with RVx202, but not RVx201, although active or latent HSV-2 was not detected at study end. In contrast, guinea pigs inoculated with wild-type HSV-2 MS (2 × 105 PFU) vaginally (n = 5) or intradermally (n = 16) developed acute disease, neurological signs, shed virus in vaginal secretions, experienced periodic recurrences throughout the study period, and had latent HSV-2 in their dorsal root and sacral sympathetic ganglia at study end. Both vaccine candidates generated neutralizing antibody. Taken together, these findings suggest that these novel vaccine candidates are safe in guinea pigs and should be tested for efficacy as preventative and/or therapeutic anti-HSV-2 vaccines.

scholarly journals Comparative Efficacy and Immunogenicity of Replication-Defective, Recombinant Glycoprotein, and DNA Vaccines for Herpes Simplex Virus 2 Infections in Mice and Guinea Pigs

2005 ◽  
Vol 79 (1) ◽  
pp. 410-418 ◽  
Author(s):  
Yo Hoshino ◽  
Sarat K. Dalai ◽  
Kening Wang ◽  
Lesley Pesnicak ◽  
Tsz Y. Lau ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Guinea Pigs ◽  
Lipid A ◽  
Neutralizing Antibody ◽  
Wild Type Virus ◽  
Monophosphoryl Lipid A ◽  
Plasmid Vaccine ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2

ABSTRACT Many candidate vaccines are effective in animal models of genital herpes simplex virus type 2 (HSV-2) infection. Among them, clinical trials showed moderate protection from genital disease with recombinant HSV-2 glycoprotein D (gD2) in alum-monophosphoryl lipid A adjuvant only in HSV women seronegative for both HSV-1 and HSV-2, encouraging development of additional vaccine options. Therefore, we undertook direct comparative studies of the prophylactic and therapeutic efficacies and immunogenicities of three different classes of candidate vaccines given in four regimens to two species of animals: recombinant gD2, a plasmid expressing gD2, and dl5-29, a replication-defective strain of HSV-2 with the essential genes UL5 and UL29 deleted. Both dl5-29 and gD2 were highly effective in attenuating acute and recurrent disease and reducing latent viral load, and both were superior to the plasmid vaccine alone or the plasmid vaccine followed by one dose of dl5-29. dl5-29 was also effective in treating established infections. Moreover, latent dl5-29 virus could not be detected by PCR in sacral ganglia from guinea pigs vaccinated intravaginally. Finally, dl5-29 was superior to gD2 in inducing higher neutralizing antibody titers and the more rapid accumulation of HSV-2-specific CD8+ T cells in trigeminal ganglia after challenge with wild-type virus. Given its efficacy, its defectiveness for latency, and its ability to induce rapid, virus-specific CD8+-T-cell responses, the dl5-29 vaccine may be a good candidate for early-phase human trials.

scholarly journals Herpes Simplex Virus 2 in Autonomic Ganglia: Evidence for Spontaneous Reactivation

2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Julianna R. Pieknik ◽  
Andrea S. Bertke ◽  
Philip R. Krause
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Sympathetic Ganglia ◽  
Viral Reactivation ◽  
Infection Model ◽  
Autonomic Ganglia ◽  
Late Gene Expression ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2 ◽  
Spontaneous Reactivation

ABSTRACTHerpes simplex virus 2 (HSV-2) can be transmitted in the presence or absence of lesions, allowing efficient spread among the general population. Recurrent HSV genital lesions are thought to arise from reactivated latent virus in sensory cell bodies of the dorsal root ganglia (DRG). However, HSV-2 has also been found latent in autonomic ganglia. Spontaneous reactivation or a low level of chronic infection could theoretically also occur in these peripheral nervous tissues, contributing to the presence of infectious virus in the periphery and to viral transmission. Use of a recently described, optimized virus with a monomeric mNeonGreen protein fused to viral capsid protein 26 (VP26) permitted detection of reactivating virus in explanted ganglia and cryosections of DRG and the sacral sympathetic ganglia (SSG) from latently infected guinea pigs. Immediate early, early, and late gene expression were quantified by droplet digital reverse transcription-PCR (ddRT-PCR), providing further evidence of viral reactivation not only in the expected DRG but also in the sympathetic SSG. These findings indicate that viral reactivation from autonomic ganglia is a feature of latent viral infection and that these reactivations likely contribute to viral pathogenesis.IMPORTANCEHSV-2 is a ubiquitous important human pathogen that causes recurrent infections for the life of its host. We hypothesized that the autonomic ganglia have important roles in viral reactivation, and this study sought to determine whether this is correct in the clinically relevant guinea pig vaginal infection model. Our findings indicate that sympathetic ganglia are sources of reactivating virus, helping explain how the virus causes lifelong recurrent disease.

scholarly journals Live Attenuated Herpes Simplex Virus 2 Glycoprotein E Deletion Mutant as a Vaccine Candidate Defective in Neuronal Spread

2012 ◽  
Vol 86 (8) ◽  
pp. 4586-4598 ◽  
Author(s):  
Sita Awasthi ◽  
Elizabeth E. Zumbrun ◽  
Huaxin Si ◽  
Fushan Wang ◽  
Carolyn E. Shaw ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Deletion Mutant ◽  
Vaccine Candidate ◽  
Glycoprotein E ◽  
Simplex Virus ◽  
Herpes Simplex Virus 2
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