Vaccines for Herpes Simplex: Recent Progress Driven by Viral and Adjuvant Immunology

Sandgren, Kerrie J.; Truong, Naomi R.; Smith, Jacinta B.; Bertram, Kirstie M.; Cunningham, Anthony L.

doi:10.1007/978-1-4939-9814-2_2

Cited by 13 publications

(9 citation statements)

References 156 publications

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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%

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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%

“…An exciting new study reports the development of a novel DNA vaccine against HSV-2 [ 146 ]. Their DNA vaccine encoded the following viral proteins: gB, gD, ICP0, ICP4 and UL39.…”

Section: Hsv Vaccination and Immunotherapiesmentioning

confidence: 99%

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

et al. 2020

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“…These results support the rationale for including one or more entry proteins as immunogens but also suggest additional antigens are needed. Attenuated live virus, subunit protein and nucleic acid vaccines for genital herpes are currently in preclinical development or human trials (10)(11)(12)(13)(14). Our candidate mRNA-LNP vaccine encodes three glycoproteins, gC2, gD2, and gE2 that are expressed on the virus envelope and at the surface of infected cells during virus replication (4).…”

Section: Introductionmentioning

confidence: 99%

Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models

Awasthi¹,

Knox²,

Desmond³

et al. 2021

Journal of Clinical Investigation

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Nucleoside-modified mRNA vaccines have gained global attention because of COVID-19. We evaluated a similar vaccine approach for preventing a chronic latent genital infection rather than an acute respiratory infection. We used animal models to compare an HSV-2 trivalent nucleoside-modified mRNA vaccine with the same antigens prepared as proteins with an emphasis on antigen-specific memory B cell responses and immune correlates of protection. In guinea pigs, serum neutralizing antibody titers were higher at one month and declined far less by eight months in mRNA-than protein-immunized animals. Both vaccines protected against death and genital lesions when infected one month after immunization; however, protection was more durable in the mRNA than protein group when infected after eight months, an interval representing >15% of the animal's lifespan. Serum and vaginal neutralizing antibody titers correlated with protection against infection as measured by genital lesions and vaginal virus titers two days post infection. In mice, the mRNA vaccine generated more antigen-specific memory B cells than the protein vaccine at early times post immunization that persisted for up to one year. High neutralizing titers and robust B cell immune memory likely explain the more durable protection by the HSV-2 mRNA vaccine.

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“…An important feature of HSV-1 and HSV-2 shared with other alphaherpes viruses is their ability to infect neurons and establish latency in the trigeminal ganglionic and dorsal root neurons, respectively [81]. Diseases caused by HSV are incurable, difficult to prevent, and clearly require efficient HSV vaccine, which does not exist yet despite more than 60 years of research [81][82][83].…”

Section: Hsvmentioning

confidence: 99%

Fight fire with fire: the need for a vaccine based on intrinsic disorder and structural flexibility

Uversky

2022

Explor Immunol

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The absence of advancement in finding efficient vaccines for several human viruses, such as hepatitis C virus (HCV), human immunodeficiency virus type 1 (HIV-1), and herpes simplex viruses (HSVs) despite 30, 40, and even 60 years of research, respectively, is unnerving. Among objective reasons for such failure are the highly glycosylated nature of proteins used as primary vaccine targets against these viruses and the presence of neotopes and cryptotopes, as well as high mutation rates of the RNA viruses HCV and HIV-1 and the capability to establish latency by HSVs. However, the lack of success in utilization of the structure-based reverse vaccinology for these viruses is likely to be related to the presence of highly flexible and intrinsically disordered regions in human antibodies (Abs) and the major immunogens of HIV-1, HCV, and HSVs, their surface glycoproteins. This clearly calls for moving from the rational structure-based vaccinology to the unstructural vaccinology based on the utilization of tools designed for the analysis of disordered and flexible proteins, while looking at intrinsically disordered viral antigens and their interactions with intrinsically disordered/flexible Abs.

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Vaccines for Herpes Simplex: Recent Progress Driven by Viral and Adjuvant Immunology

Cited by 13 publications

References 156 publications

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Trivalent nucleoside-modified mRNA vaccine yields durable memory B cell protection against genital herpes in preclinical models

Fight fire with fire: the need for a vaccine based on intrinsic disorder and structural flexibility

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