HSV-2: in pursuit of a vaccine

Abstract

Herpes simplex virus type 2 (HSV-2) is one of the most prevalent sexually transmitted infections worldwide. In addition to recurrent genital ulcers, HSV-2 causes neonatal herpes, and it is associated with a 3-fold increased risk for HIV acquisition. Although many HSV-2 vaccines have been studied in animal models, few have reached clinical trials, and those that have been tested in humans were not consistently effective. Here, we review HSV-2 pathogenesis, with a focus on novel understanding of mucosal immunobiology of HSV-2, and vaccine efforts to date, in an attempt to stimulate thinking about future directions for development of effective prophylactic and therapeutic HSV-2 vaccines.

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

“…As in previous vaccine studies (17,27), HSV-2 was more pathogenic and difficult to contain by immunological measures compared to HSV-1. At 1 LD 50 , the HSV-2 isolate yielded symptomatic infection in all naive and mock-vaccinated animals and killed more than 60% of the animals.…”

“…Among the eight fully protected animals, as judged by the absence of clinical signs postchallenge, only two were, in fact, infected, whereas there was no trace of the virus in the remaining vaccinees. In all, vLAW-gB1/VSV was able to protect from HSV-2 infection and severe disease, as defined by clinical score 2 or higher, 38 and 80% animals, respectively, thus outperforming most previously developed vaccines based on the sole gB (14,27). Protection efficacy was further addressed against a challenge dose 10 times higher than in the above tests and that killed nearly all of the naive and mock-vaccinated controls.…”

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

“…As in previous vaccine studies (17,27), HSV-2 was more pathogenic and difficult to contain by immunological measures compared to HSV-1. At 1 LD 50 , the HSV-2 isolate yielded symptomatic infection in all naive and mock-vaccinated animals and killed more than 60% of the animals.…”

“…Among the eight fully protected animals, as judged by the absence of clinical signs postchallenge, only two were, in fact, infected, whereas there was no trace of the virus in the remaining vaccinees. In all, vLAW-gB1/VSV was able to protect from HSV-2 infection and severe disease, as defined by clinical score 2 or higher, 38 and 80% animals, respectively, thus outperforming most previously developed vaccines based on the sole gB (14,27). Protection efficacy was further addressed against a challenge dose 10 times higher than in the above tests and that killed nearly all of the naive and mock-vaccinated controls.…”

Therapeutic prime/pull vaccination of HSV-2-infected guinea pigs with the ribonucleotide reductase 2 (RR2) protein and CXCL11 chemokine boosts antiviral local tissue-resident and effector memory CD4 + and CD8 + T cells and protects against recurrent genital herpes

“…This study demonstrated the efficacy of immunization in reducing the frequency of recurrences (20). In recent years, several sub-clinical experiments have supported these preclinical findings using protein-based subunit vaccines, often administered with a potent adjuvant (a substance that enhances the immune response) (21). Vaccination with these proteins has been found to reduce the rates of recurrent lesions (visible outbreaks) or recurrent shedding by approximately 50% (22).…”

Functional Characterization of Ocular-Derived Human Alphaherpesvirus Cross-Reactive CD4 T Cells

“…These responses are of potential interest for vaccine development to confer cross-protection but may also be involved in immunopathogenesis. Whereas various aHHV cross-reactive B cell target Ags have been identified (52)(53)(54), T cell immunity directed to multiple aHHV is restricted to HSV-1 and HSV-2 (29,55,56). The current study reports three main findings.…”

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

“…As in previous vaccine studies (17,27), HSV-2 was more pathogenic and difficult to contain by immunological measures compared to HSV-1. At 1 LD 50 , the HSV-2 isolate yielded symptomatic infection in all naive and mock-vaccinated animals and killed more than 60% of the animals.…”

“…Among the eight fully protected animals, as judged by the absence of clinical signs postchallenge, only two were, in fact, infected, whereas there was no trace of the virus in the remaining vaccinees. In all, vLAW-gB1/VSV was able to protect from HSV-2 infection and severe disease, as defined by clinical score 2 or higher, 38 and 80% animals, respectively, thus outperforming most previously developed vaccines based on the sole gB (14,27). Protection efficacy was further addressed against a challenge dose 10 times higher than in the above tests and that killed nearly all of the naive and mock-vaccinated controls.…”

Therapeutic prime/pull vaccination of HSV-2-infected guinea pigs with the ribonucleotide reductase 2 (RR2) protein and CXCL11 chemokine boosts antiviral local tissue-resident and effector memory CD4 + and CD8 + T cells and protects against recurrent genital herpes

“…This study demonstrated the efficacy of immunization in reducing the frequency of recurrences (20). In recent years, several sub-clinical experiments have supported these preclinical findings using protein-based subunit vaccines, often administered with a potent adjuvant (a substance that enhances the immune response) (21). Vaccination with these proteins has been found to reduce the rates of recurrent lesions (visible outbreaks) or recurrent shedding by approximately 50% (22).…”

Functional Characterization of Ocular-Derived Human Alphaherpesvirus Cross-Reactive CD4 T Cells

“…These responses are of potential interest for vaccine development to confer cross-protection but may also be involved in immunopathogenesis. Whereas various aHHV cross-reactive B cell target Ags have been identified (52)(53)(54), T cell immunity directed to multiple aHHV is restricted to HSV-1 and HSV-2 (29,55,56). The current study reports three main findings.…”

A Lentiviral Vector-Based, Herpes Simplex Virus 1 (HSV-1) Glycoprotein B Vaccine Affords Cross-Protection against HSV-1 and HSV-2 Genital Infections

“…As in previous vaccine studies (17,27), HSV-2 was more pathogenic and difficult to contain by immunological measures compared to HSV-1. At 1 LD 50 , the HSV-2 isolate yielded symptomatic infection in all naive and mock-vaccinated animals and killed more than 60% of the animals.…”

“…Among the eight fully protected animals, as judged by the absence of clinical signs postchallenge, only two were, in fact, infected, whereas there was no trace of the virus in the remaining vaccinees. In all, vLAW-gB1/VSV was able to protect from HSV-2 infection and severe disease, as defined by clinical score 2 or higher, 38 and 80% animals, respectively, thus outperforming most previously developed vaccines based on the sole gB (14,27). Protection efficacy was further addressed against a challenge dose 10 times higher than in the above tests and that killed nearly all of the naive and mock-vaccinated controls.…”

Therapeutic prime/pull vaccination of HSV-2-infected guinea pigs with the ribonucleotide reductase 2 (RR2) protein and CXCL11 chemokine boosts antiviral local tissue-resident and effector memory CD4 + and CD8 + T cells and protects against recurrent genital herpes

“…This study demonstrated the efficacy of immunization in reducing the frequency of recurrences (20). In recent years, several sub-clinical experiments have supported these preclinical findings using protein-based subunit vaccines, often administered with a potent adjuvant (a substance that enhances the immune response) (21). Vaccination with these proteins has been found to reduce the rates of recurrent lesions (visible outbreaks) or recurrent shedding by approximately 50% (22).…”

Functional Characterization of Ocular-Derived Human Alphaherpesvirus Cross-Reactive CD4 T Cells

“…These responses are of potential interest for vaccine development to confer cross-protection but may also be involved in immunopathogenesis. Whereas various aHHV cross-reactive B cell target Ags have been identified (52)(53)(54), T cell immunity directed to multiple aHHV is restricted to HSV-1 and HSV-2 (29,55,56). The current study reports three main findings.…”