Characteristics of herpes simplex virus infection and pathogenesis suggest a strategy for vaccine development

Xu, Xingli; Zhang, Ying; Li, Qihan

doi:10.1002/rmv.2054

Cited by 45 publications

(44 citation statements)

References 141 publications

(136 reference statements)

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“…There are several recent reviews that addressed the advancement of HSV vaccine design and discussed numerous emerging HSV candidate vaccines [ 144 , 145 , 146 ]. In this section we provide an update to this discussion by highlighting the new published findings in the search for novel prophylactic and therapeutic HSV vaccines not captured in prior reviews.…”

Section: Hsv Vaccination and Immunotherapiesmentioning

confidence: 99%

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

et al. 2020

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Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

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Section: Hsv Vaccination and Immunotherapiesmentioning

confidence: 99%

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

et al. 2020

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“…Skin symptoms include vesicular lesions on an erythematous base. Lesions drive to the focal damage of the epithelial layer and a widespread infiltrate of inflammatory cells elaborates in the surrounding rim and the underlying dermal layer [15,18]. It has been estimated that 10-30% of new infections are symptomatic.…”

Section: Epidemiology and Pathogenesis Of Hsv Infectionmentioning

confidence: 99%

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development

Treml

Gazdová

Šmejkal

et al. 2020

Viruses

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Recently, the problem of viral infection, particularly the infection with herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), has dramatically increased and caused a significant challenge to public health due to the rising problem of drug resistance. The antiherpetic drug resistance crisis has been attributed to the overuse of these medications, as well as the lack of new drug development by the pharmaceutical industry due to reduced economic inducements and challenging regulatory requirements. Therefore, the development of novel antiviral drugs against HSV infections would be a step forward in improving global combat against these infections. The incorporation of biologically active natural products into anti-HSV drug development at the clinical level has gained limited attention to date. Thus, the search for new drugs from natural products that could enter clinical practice with lessened resistance, less undesirable effects, and various mechanisms of action is greatly needed to break the barriers to novel antiherpetic drug development, which, in turn, will pave the road towards the efficient and safe treatment of HSV infections. In this review, we aim to provide an up-to-date overview of the recent advances in natural antiherpetic agents. Additionally, this paper covers a large scale of phenolic compounds, alkaloids, terpenoids, polysaccharides, peptides, and other miscellaneous compounds derived from various sources of natural origin (plants, marine organisms, microbial sources, lichen species, insects, and mushrooms) with promising activities against HSV infections; these are in vitro and in vivo studies. This work also highlights bioactive natural products that could be used as templates for the further development of anti-HSV drugs at both animal and clinical levels, along with the potential mechanisms by which these compounds induce anti-HSV properties. Future insights into the development of these molecules as safe and effective natural anti-HSV drugs are also debated.

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“…Pattern recognition receptor and/or adapter function is inhibited by viral proteins UL37, ICP0, UL36USP, US3, and ICP34.5; interferon-regulatory factors (IRF) are interfered with by US3, US11, ICP34.5, VP24, ICP27, and ICP0; and NF-kB functionality is inhibited by UL36USP, US3, and ICP0. Furthermore, JAK/STAT signaling is blunted by the action of viral proteins VR3, UL13, UL41, and ICP27 [21] (see also References [22,23]).…”

Section: A Priori Concerns Regarding Possible Obstacles To the Succesmentioning

confidence: 99%

Herpes Simplex Viruses Whose Replication Can Be Deliberately Controlled as Candidate Vaccines

Voellmy¹,

Bloom

Vilaboa

2020

Vaccines

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Over the last few years, we have been evaluating a novel paradigm for immunization using viruses or virus-based vectors. Safety is provided not by attenuation or inactivation of vaccine viruses, but by the introduction into the viral genomes of genetic mechanisms that allow for stringent, deliberate spatial and temporal control of virus replication. The resulting replication-competent controlled viruses (RCCVs) can be activated to undergo one or, if desired, several rounds of efficient replication at the inoculation site, but are nonreplicating in the absence of activation. Extrapolating from observations that attenuated replicating viruses are better immunogens than replication-defective or inactivated viruses, it was hypothesized that RCCVs that replicate with wild-type-like efficiency when activated will be even better immunogens. The vigorous replication of the RCCVs should also render heterologous antigens expressed from them highly immunogenic. RCCVs for administration to skin sites or mucosal membranes were constructed using a virulent wild-type HSV-1 strain as the backbone. The recombinants are activated by a localized heat treatment to the inoculation site in the presence of a small-molecule regulator (SMR). Derivatives expressing influenza virus antigens were also prepared. Immunization/challenge experiments in mouse models revealed that the activated RCCVs induced far better protective immune responses against themselves as well as against the heterologous antigens they express than unactivated RCCVs or a replication-defective HSV-1 strain. Neutralizing antibody and proliferation responses mirrored these findings. We believe that the data obtained so far warrant further research to explore the possibility of developing effective RCCV-based vaccines directed to herpetic diseases and/or diseases caused by other pathogens.

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Characteristics of herpes simplex virus infection and pathogenesis suggest a strategy for vaccine development

Cited by 45 publications

References 141 publications

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Natural Products-Derived Chemicals: Breaking Barriers to Novel Anti-HSV Drug Development

Herpes Simplex Viruses Whose Replication Can Be Deliberately Controlled as Candidate Vaccines

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