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Results for “Herpes Simplex Virus Vaccines”

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At least 19 recordsLinked to original sources
PubMed2005

Glycoprotein D adjuvant herpes simplex virus vaccine.

Herpes simplex virus (HSV) Type-1 and -2 are common infections that can cause primary and recurrent herpes labialis and genitalis, as well as gingivostomatitis, keratoconjunctivitis, encephalitis, disseminated infections in immunocompromised persons and neonatal infections. Despite several decades of HSV vaccine development, no effective vaccine has been developed until recently. The following review of the genital HSV-2 glycoprotein D (gD2t, t is for truncated) subunit vaccine formulated with a new adjuvant (AS04) containing alum and 3-O deacylated monophosphoryl lipid A (MPL) provides a background in which to evaluate the vaccine as well as a brief review of other approaches to herpes vaccines. The gD2t-AS04 vaccine has been demonstrated to be safe in several large clinical trials. In two trials, the vaccine reduced genital herpes disease by 73 and 74%, but only in females with no previous HSV infection. A large ongoing trial in HSV seronegative females will provide additional data on protection from HSV disease and infection.

Adjuvants, Immunologic↗
PubMed2004

Clinical trials of prophylactic and therapeutic herpes simplex virus vaccines.

Herpes simplex virus type 2 (HSV-2) is a suitable target for a vaccine, despite available antiviral therapies, because the virus causes lifelong infection and significant medical and psychosocial morbidity. A vaccine has the potential to reduce HSV acquisition, disease severity and the number of cases of neonatal herpes. It could also reduce transmission of HIV, which is epidemiologically linked to HSV. Prophylactic vaccines for HSV-2 must give broad and durable immunity across all mucosal surfaces to be effective. This is a significant challenge, as the major determinants of effective immunity have not yet been identified. Even if full protection cannot be achieved, vaccines would still be useful if they could increase the threshold of infection, or prevent clinical disease. However, it is possible that a vaccine could reduce symptomatic disease, but not eliminate asymptomatic shedding, which could inadvertently increase transmission from individuals who believe they are not infectious. Investigated prophylactic vaccines for HSV-2, including subunit vaccines encoding HSV glycoproteins packaged with adjuvants, have shown some benefits. The Chiron gD2gB2-MF59 vaccine gave transient protection of less than 6 months. The GlaxoSmithKline gD2-alum MPL vaccine conferred a 73-74% reduction in acquisition of symptomatic HSV-2 disease and a 38-42% reduction in the acquisition of HSV-2 infection in HSV-seronegative women, but gave no protection in men or HSV-1 seropositive women. Therapeutic vaccines aim to prevent HSV recurrences or minimise disease severity and duration, thereby reducing transmission. Research indicates that to be effective, therapeutic vaccines need to stimulate strong cell-mediated immune responses. Vaccines have induced HSV-specific antibody responses alone but have failed to protect recipients from recurrences. Further research is needed to define determinants of immunity to HSV-2, including identifying HSV-2 antigens, in order to design more effective vaccines.

Clinical Trials as Topic↗
PubMed1999

Herpes simplex virus vaccines.

Herpes simplex virus (HSV) infections are common and produce not only a primary infection, but also latent and recurrent infections. Therefore, the goals of a HSV vaccine are different from other vaccines. In this review, the goals of both prophylactic and therapeutic HSV vaccines are discussed and related to the immunobiology of acute and recurrent HSV infections. Next, the vaccine strategies that have been and are being evaluated for control of HSV disease are described. Current approaches take advantage of many of the modern methodologies for vaccine development. Thus, as we await final evaluations of subunit HSV glycoprotein vaccines, early phase I trails are evaluating newer vaccine approaches including DNA-based vaccines and replication-impaired viruses. The definitive HSV vaccine may await increased knowledge of the optimal viral antigen(s) and routes to induce genital tract immunity.

Animals↗
PubMedDate not supplied

Multicentre clinical trial with herpes simplex virus vaccine in recurrent herpes infection.

The aim of this work was to confirm our preliminary clinical and immunological evaluation of the protective effects of a herpes simplex virus (HSV) vaccine derived from killed virus in the treatment of relapsing facial or genital herpes simplex infection. A total of 142 patients were treated with the HSV vaccine and a control group of 50 were treated with intermittent oral acyclovir (ACV). The vaccine reduced annual active disease days in vaccinees to 11.59 (+/- 15.3) after treatment (65.11 +/- 31.64 before treatment) compared to 30.4 +/- 17.49 days after treatment of the control group patients (71.86 +/- 32.5 before treatment).

Acyclovir↗
PubMed2005

Implications for herpes simplex virus vaccine strategies based on antibodies produced to herpes simplex virus type 1 glycoprotein gC immune evasion domains.

Herpes simplex virus type I (HSV-1) glycoprotein gC (gC-1) is an immune evasion molecule that inhibits complement activation by binding C3b. Three assays were used to assess whether IgG antibodies produced by HSV-1 infection in humans block the interaction between C3b and gC-1. In two assays human IgG had no effect, while in one assay IgG partially inhibited C3b binding, which occurred at IgG concentrations approaching the upper limits of those found in human serum. Mice infected with HSV-1 produced antibodies that partially blocked C3b binding at lower IgG concentrations than human IgG. Importantly, gC-1 immunization in mice produced higher titers of gC-1 antibodies than infection. We previously reported that gC-1 immunization in mice totally blocks C3b binding and reduces disease severity. Therefore, gC-1 immunization in humans may also induce blocking antibodies that modify disease, despite the rather limited ability of infection to produce these antibodies.

Animals↗
PubMed1988

Hypothetical vaccination of the Dutch population with a herpes simplex virus vaccine: estimation of the profitability using a demographic projection model.

The apparently increasing evidence of herpes simplex virus infections of the genital tract has focused attention on preventing the infection by vaccination. Herpes genitalis is not, however, the most quantitatively important clinical manifestation of herpes simplex virus infections. Because 41% of the hospitalized patients are younger than 20 years, vaccination of birth cohorts would be more favourable. In this paper the financial benefits of a hypothetical herpes simplex virus vaccination were calculated with the use of a population projection model. For the Netherlands, if the price of the hypothetical herpes simplex virus vaccine equals the cost price of the mumps component of the combined mumps-measles-rubella vaccine, the herpes vaccine would be profitable within 8 years.

Adolescent↗
PubMed1980

Restriction of latent herpes virus infection in rabbits immunized with subviral herpes simplex virus vaccine.

The ability of an experimental herpes simplex virus type 1 (HSV) vaccine to influence the establishment of latent infection was examined. The virion-free vaccine was prepared from HSV 1-infected LEP cells by extraction with Nonidet P 40. Albino rabbits were immunized with three doses of the subviral vaccine (strain KOS) and challenged with 10(5) PFU of HSV 1 (Kupka strain) into the right scarified cornea. Non-immune controls and rabbits immunized with formalin-inactivated virion vaccine (strain KOS) were infected in a similar way. At intervals from 53 to 164 days p. i., the animals were killed and fragments of both trigeminal ganglia were kept separately in culture for 10 days. In 18 out of 22 immunized animals (81.8%), latency was established in the homolateral Gasserian ganglion. The proportion of HSV-yielding fragments, was considerably higher in ganglia from non-immune animals (42.6%) as compared to those from ganglia of rabbits immunized with the subviral vaccine (5.4%) or with the whole virion vaccine (14.6%). The immunity resulting from previous vaccination restricted about 5 times the number of ganglion cells, which become virus carriers.

Animals↗
PubMed1986

The quest for a herpes simplex virus vaccine: background and recent developments.

Herpes simplex virus infections in humans range from localized skin infections of the oral, ocular and genital regions, to severe and often fatal disseminated infections of immunocompromised hosts. Following primary infection, the virus often becomes established in a latent form in the neurons of sensory ganglia and can reactivate to excrete virus asymptomatically or produce recrudescent lesions. This review describes some of the mechanisms involved in the immune response against HSV infections and examines the different strategies adopted to develop a vaccine against this seemingly intractable disease.

Animals↗
PubMedDate not supplied

Introduction: objectives of herpes simplex virus vaccines seen from a historical perspective.

Herpes simplex virus (HSV) types 1 and 2 cause a variety of severe manifestations in humans. A major characteristic of HSVs is their ability to establish latent infection in sensory ganglia, where these viruses are shielded from the immune system and are impervious to the action of antiviral drugs known to date. Ideally, HSV-induced clinical syndromes should be prevented by vaccination, but two major problems arise. First, although many antiviral vaccines have successfully prevented disease, none have prevented infection. Once the virus infects cells at the portal of entry of the infection, it can establish latent infection in sensory neurons that innervate the cell. Second, while HSV disease primarily affects adults greater than 18 years of age, mass immunization in the United States is effectively carried out in the interval between nursery school and high school, and yet the vaccines must confer protection for a long time after vaccination. The central issues involved in the development of an anti-HSV vaccine include what type of vaccine should be developed, what we should expect from an HSV vaccine, and how we should monitor the effectiveness of the vaccine.

Herpes Simplex↗
PubMed1983

Comparison of effects of adjuvants on efficacy of virion envelope herpes simplex virus vaccine against labial infection of BALB/c mice.

A subunit virion envelope vaccine of herpes simplex virus type 1 was evaluated for its ability to protect labially infected mice from development of the primary herpetic lesion, encephalitic death, and latent virus infection in the trigeminal ganglion. Several adjuvants, including aluminum hydroxide and polyriboinosinic acid-polyribocytidylic acid complexed with poly-L-lysine and carboxymethyl cellulose were investigated for their ability to enhance protection of the subunit vaccine and were compared in effectiveness with complete Freund adjuvant. The subunit vaccine was demonstrated to be immunogenic, as shown by development of antibody detectable by an enzyme-linked immunosorbent assay. The humoral immune response was correlated with protection from herpetic encephalitis and, at a lower degree, with prevention of the appearance of primary herpetic lesions and acceleration of lesion resolution. The efficacy of the vaccine was most apparent in protecting mice from encephalitic death. To reduce or prevent the development of latent infection was most difficult, but was achieved with some vaccine regimens. Repeated administrations of vaccine with adjuvant were required for this protection. The most effective adjuvant was complete Freund adjuvant, but several synthetic adjuvants were effective, particularly aluminum hydroxide and the polyriboinosinic-polyribocytidylic acid-poly-L-lysine-carboxymethyl cellulose immunoadjuvant.

Adjuvants, Immunologic↗
PubMed2006

[Herpes simplex virus vaccines: perspectives].

PURPOSE: Despite effective antiviral therapy, infection with herpes simplex virus (HSV) is a critical public health issue, particularly genital herpes by its social and psychological burden and its contribution to the neonatal herpes and possibly to the HIV/AIDS pandemic. CURRENT KNOWLEDGE: Many prophylactic and therapeutic vaccination approaches have been explored but no effective vaccine is presently available. In fact, as members of the Herpesviridae family, both HSV-1 and 2 types have genes involved in immune evasion. FUTURE PROSPECTS: Further research is needed to define determinants of immunity in order to design more effective vaccines.

Clinical Trials, Phase III as Topic↗
PubMed1976

Immunology of herpes simplex virus infection: relevance to herpes simplex virus vaccines and cervical cancer.

The immunology of herpes simplex infections has been reviewed, particularly in relation to potential herpes simplex virus (HSV) vaccines, and to the association between HSV and cervical cancer. Relevant data from humans, experimental animals, and in vitro systems implicate both specific immune mechanisms and nonspecific factors in the course of HSV infections. There appear to be complex interactions between the various populations of mononuclear cells, marcrophages, and lymphokines or other humoral factors. It is not yet possible, however, to pinpoint the crucial factors determining the different manifestations of the viral infection (primary infection, endogenous recurrence, or exogenous reinfection) in the various human hosts, although genetic factors may be important. While numerous animal models of HSV infection are available for the evaluation of HSV vaccines, models of HSV-induced cervical cancer require further exploration.

Age Factors↗
PubMed1999

The affinity adsorptive recovery of an infectious herpes simplex virus vaccine.

The chromatographic purification of a recombinant Herpes Simplex Virus (type 2) from salt- and heparin-released harvests of infected complementing Vero (CR2) cells is addressed. Functionalized matrices and process operating conditions are identified that provide adequate virus titres in eluates that are significantly reduced in CR2 cell protein and DNA and possess a low level of HSV-2 protein. Virus from diluted salt-released harvests (0.14 M NaCl) was not appreciably adsorbed onto either heparin-Sepharose or Cellufine-heparin matrices but was virtually completely adsorbed onto Cellufine-sulfate and heparin-HP matrices. Virus was recovered by either a linear salt gradient elution (0.14-2 M NaCl) or by a single-step elution with 1.5 M NaCl in phosphate buffer. Recoveries of infectious virus with step elution were 21% and 89%, respectively, for these matrices. Virus from undiluted salt-released harvest (0.8 M NaCl) was substantially adsorbed onto Cellufine-sulfate gel (44% adsorption) and completely adsorbed onto heparin-HP matrices. This virus was recovered with high yield by either gradient or step elution with phosphate-buffered saline. Finally, heparin-harvested virus was fed directly to these matrices and quantitatively adsorbed. The virus could be completely recovered from the heparin-HP matrix with 1.5 M NaCl buffer to provide a purified preparation containing only 0.05 pg protein/pfu and 1.2 x 10(-4) pg DNA/pfu.

Adsorption↗
PubMed1982

Application of molecular genetics to the design of live herpes simplex virus vaccines.

In principle, several avenues for attenuation of herpes simplex viruses (HSV) are now available. These include intermixing of HSV-1 and HSV-2 genes by recombination, altering the regulation of gene expression and the deletion of viral genes not required for replication of the virus in permissive cells in culture. Results of analyses of HSV-1 x HSV-2 recombinants and of mutants containing a deletion in a gene expressed early in infection showed a loss of virulence when infected by intracerebral route into adult Balb/c mice. In addition, immunization of the mice by intracerebral route with relatively low doses of virus protected the mice from challenge with high doses (3000 LD50) of virulent virus. The application of genetic engineering to the construction of live vaccines is discussed.

Chromosome Deletion↗
PubMedDate not supplied

Evaluation of herpes simplex virus vaccines in animals: the guinea pig vaginal model.

The guinea pig model of genital herpes has proved useful for the evaluation of experimental herpes simplex virus vaccines. The model shares many of the features of genital herpes in humans, including a natural route of inoculation that results in self-limiting primary vulvovaginitis. Latent infection is established in sensory ganglia, and animals experience both spontaneous and ultraviolet radiation-induced recurrence of infection. Many humoral, cellular, and cytokine responses to herpes simplex virus type 2 infection in the guinea pig have been characterized. Both inactivated subunit immunogens and live, attenuated virus have been shown to afford some protection against primary disease, although they generally do not prevent acute viral replication or the establishment of latency. Because latently infected guinea pigs experience recurrent infections, this model has been used to explore immunotherapeutic approaches to the control of recurrent disease. With the development of more defined immunologic reagents, this model should prove useful for exploring the immune responses that are important in the control of primary, latent, and recurrent herpes simplex virus type 2 infections.

Animals↗
PubMed2005

Pediatrics and herpes simplex virus vaccines.

This review explores the development of prophylactic genital herpes vaccines and their potential impact on perinatal and oral-facial disease. Vaccine strategies have included the use of whole killed virus, viral subunits, attenuated live virus, viral vectors, and bare DNA. To date, the recombinant subunit vaccine, truncated HSV-2 gD and alum/MPL, has been the most efficacious. The vaccine is 73 to 74 percent effective in preventing genital disease in herpes simplex virus seronegative women but is not effective in men or seropositive women. Models predict a significant impact on genital herpes if it limits viral shedding. Reductions in perinatal and oral-facial disease are likely to occur as well. Once an efficacious herpes vaccine is available, its effectiveness will depend ultimately on vaccine acceptance by professional organizations, healthcare professionals, and parents. Further research is required to improve on and fully understand the implications of prophylactic herpes simplex vaccines.

Child↗
PubMed2005

A randomized controlled trial of a replication defective (gH deletion) herpes simplex virus vaccine for the treatment of recurrent genital herpes among immunocompetent subjects.

BACKGROUND: A replication incompetent herpes virus lacking the glycoprotein H gene has been developed as a potential therapeutic vaccine for genital herpes. GOAL: To determine vaccine efficacy on reducing HSV reactivation and clinical disease among immunocompetent persons with recurrent genital HSV-2 infection. STUDY DESIGN: Randomized multicenter placebo-controlled trial. Healthy volunteers who had six or more recurrences of genital herpes per year were randomized to receive injections of vaccine at 0 and 8 or 0, 4, and 8 or 0, 2, 4, and 8 weeks or placebo and were followed for subsequent recurrences for 1 year. RESULTS: The median times to first recurrence of genital herpes (40 days versus 30 days versus 37 days versus 42 days, respectively), mean number of recurrences (3 versus 3 versus 2.4 versus 1.9, respectively), and time to lesion healing of the first recurrence (8 days versus 7.8 days versus 7.4 days versus 7.5 days, respectively), were similar for all treatment groups. Asymptomatic viral shedding was detected by PCR in 61/74 (82%) persons performing daily sample collection following completion of the vaccination series. No differences were noted in the proportion of days with shedding between treatment groups (11.9% versus 17.2% versus 13.1% versus 16.4%, respectively). CONCLUSION: This replication incompetent HSV-2 vaccine lacking the glycoprotein H gene was safe but had no clinical or virologic benefit in the amelioration of genital HSV-2 disease among immunocompetent men and women.

Adolescent↗