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Herpes simplex virus 1 and 2 infections cause high unmet disease burdens worldwide. Mainly HSV-2 causes persistent sexually transmitted disease, fatal neonatal disease and increased transmission of HIV/AIDS. Thus, there is an urgent requirement to develop effective vaccines. We developed nucleic acid vaccines encoding a novel virus entry complex stabilising cell membrane fusion, 'virus-like membranes', VLM. Two dose intramuscular immunisations using DNA expression plasmids in a guinea pig model gave 100% protection against acute disease and significantly reduced virus replication after virus intravaginal challenge. There was also reduced establishment of latency within the dorsal root ganglia and spinal cord, but recurrent disease and recurrent virus shedding remained. To increase cellular immunity and protect against recurrent disease, cDNA encoding an inhibitor of chemokine receptors on T regulatory cells was added and compared to chemokine CCL5 effects. Immunisation including this novel human chemokine gene, newly defined splice variant from an endogenous virus genome, 'virokine immune therapeutic', VIT, protected most guinea pigs from recurrent disease and reduced recurrent virus shedding distinct from a gD protein vaccine similar to that previously evaluated in clinical trials. All DNA vaccines induced significant neutralising antibodies and warrant evaluation for new therapeutic treatments. [ABSTRACT FROM AUTHOR]

Herpes simplex virus type 1 and 2 (HSV-1 and HSV-2 respectively) cause life-long latent infections resulting in recurrent orofacial and genital blisters or sores. Ensued disease can be painful and may lead to significant mental anguish of infected individuals. Currently, there are no FDA-approved vaccines for either prophylactic or therapeutic use, and recent clinical trials of subunit vaccines failed to achieve endpoints goals. Development of a safe live-attenuated herpes simplex vaccine may provide the antigenic breadth to ultimately protect individuals from acquiring HSV disease. We have previously shown that prophylactic use of the non-neurotropic live attenuated HSV-1 vaccine, VC-2, provides potent and durable protection from genital HSV-2 disease in the guinea pig model. Here, we investigated the effects of intradermal administration as well as the deletion of the viral glycoprotein G (gG) on the efficacy of prophylactic vaccination. Vaccination with either VC-2, VC-2 gG null, or gD2 MPL/Alum offered robust protection from acute disease regardless of route of vaccination. However, both the VC-2 gG-null and the ID vaccination route were more effective compared to the parent VC2 administered by the IM route. Specifically, the VC-2 gG-null administered ID, reduced HSV-2 vaginal replication on day 2 and day 4 as well as mean recurrent lesion scores more effectively than VC2 administered IM. Most importantly, only VC-2 gG null IM and VC-2 ID significantly reduced the frequency of recurrent shedding, the most likely source for virus transmission. Similarly, while all vaccinated groups demonstrated a significant reduction in the number of animals testing PCR-positive for HSV-2 in their dorsal root ganglia following challenge only VC2 ID vaccinated animals demonstrated a significant reduction in DRG viral load. All vaccinations induced neutralizing antibodies to HSV-2 MS when compared to unvaccinated guinea pigs. Therefore, further investigation of VC-2 gG null delivered ID is warranted. [ABSTRACT FROM AUTHOR]

Background Congenital cytomegalovirus infection can be life-threatening and often results in significant developmental deficits and/or hearing loss. Thus, there is a critical need for an effective anti-CMV vaccine. Objective To determine the efficacy of replication-defective lymphocytic choriomeningitis virus (rLCMV) vectors expressing the guinea pig CMV (GPCMV) antigens, gB and pp65, in the guinea pig model of congenital CMV infection. Methods Female Hartley strain guinea pigs were divided into three groups: Buffer control group ( n = 9), rLCMV-gB group ( n = 11), and rLCMV-pp65 ( n = 11). The vaccines were administered three times IM at 1.54 × 10 6 FFU per dose at 21-day intervals. At two weeks after vaccination, the female guinea pigs underwent breeding. Pregnant guinea pigs were challenged SQ at ∼45–55 days of gestation with 1 × 10 5 PFU of GPCMV. Viremia in the dams, pup survival, weights of pups at delivery, and viral load in both dam and pup tissues were determined. Results Pup survival was significantly increased in the LCMV-gB vaccine group. There was 23% pup mortality in the gB vaccine group ( p = 0.044) and 26% pup mortality in the pp65 vaccine group ( p = 0.054) compared to 49% control pup mortality. The gB vaccine induced high levels of gB binding and detectable neutralizing antibodies, reduced dam viremia, and significantly reduced viral load in dam tissues compared to control dams ( p < 0.03). Reduced viral load and transmission in pups born to gB-vaccinated dams was observed compared to pups from pp65-vaccinated or control dams. Conclusions The rLCMV-gB vaccine significantly improved pup survival and also increased pup weights and gestation time. The gB vaccine was also more effective at decreasing viral load in dams and pups and limiting congenital transmission. Thus, rLCMV vectors that express CMV antigens may be an effective vaccine strategy for congenital CMV infection. [ABSTRACT FROM AUTHOR]

Abstract: Animal models for the evaluation of therapies against human cytomegalovirus (HCMV) are limited due to the species-specific replication of CMV. Models utilizing human fetal tissues implanted into SCID mice have been used but tend to be labor intensive and require human tissues. We therefore developed a model using HCMV-infected human foreskin fibroblasts (HFF) seeded onto a biodegradable gelatin matrix (Gelfoam). Infected HFFs are then implanted subcutaneously into SCID mice. We next evaluated two antivirals in this model. Treatment from days 0 to 5 with ganciclovir (GCV) produced a marginally significant reduction in viral titer while treatment from days 0 to 14 resulted in a more significant reduction in viral titers of 1.47log10 pfu/ml (P <0.0001). Viral titers were similarly reduced in a group receiving GCV treatment from days 7 to 14 post-implantation (1.50log10 pfu/ml, P <0.0001). Cidofovir therapy from days 7 to 14 reduced viral titers by almost 2log10 pfu/ml (from 3.51±0.31log10 pfu/ml in untreated animals to 1.56±0.40log10 pfu/ml in treated animals, P <0.0001). These results indicate that the Gelfoam-HCMV SCID mouse model is suitable for the in vivo evaluation of new antivirals against HCMV and is simpler and more convenient than previous models. [Copyright &y& Elsevier]

Background. Cytomegalovirus (CMV) infection of the fetus is the leading cause of congenital infection. Using the guinea pig model of congenital CMV infection, we sought to determine whether antiviral treatment of a CMV- infected dam could improve the outcome of offspring. Methods. Pregnant Hartley guinea pigs were inoculated with guinea pig CMV (GPCMV) during the late second/early third trimester of gestation. Guinea pigs received either 1 dose of cyclic 1-[((s)-2-hydroxy-2-oxo-1,4,2,-dioxaphosphorinan-5-yl)methyl]cytosine dihydrate (cHPMPC; 35 mg/kg) or placebo 24 h after GPCMV infection. Guinea pigs were monitored until delivery or were killed 10 days after infection, for the evaluation of the effect of cHPMPC on viral replication by polymerase chain reaction analysis in various dam and pup tissues. Results. cHPMPC treatment of infected dams improved pup survival from 28.2% (11/39) to 83.7% (36/43) (P< .001) and extended the duration of pregnancy. cHPMPC treatment did not prevent infection of the placenta or disseminated infection of the dam and pup but significantly decreased the amount of GPCMV in tissues. GPCMV DNA levels in the placenta were reduced from 3.54 to 2.12 log10 genome copies/μg of DNA (P< .0001). Conclusions. Treatment of the GPCMV-infected pregnant dam with 1 dose of cHPMPC improves the outcome of congenital infection and decreases viral replication in a guinea pig model. [ABSTRACT FROM AUTHOR]

Cytomegalovirus (CMV) is the most common cause of congenital infection in the developed world and can lead to a life-threatening disease. We therefore developed an animal model to evaluate candidate anti-CMV drugs and to further define the pathogenesis of CMV infections. Newborn guinea pigs were infected by intraperitoneal administration of 106 pfu of a virulent salivary gland (SG) passaged guinea pig CMV (gpCMV) within 48 h of birth. Inoculation of animals produced 50% overall mortality. A lack of weight gain was also a hallmark of infection. By day 14 after inoculation the weight of gpCMV-infected animals was significantly less than controls (152.9±45 g versus 254.7±38.5 g, P<0.0001). The most consistent isolation and highest titers of virus were found in the liver and spleen early while lung titers were maximal at day 10. A quantitative competitive PCR (qcPCR) assay confirmed the presence of a high CMV viral load in infected organs. Antiviral treatment with cyclic HPMPC (cHPMPC) for 7 days significantly reduced mortality (1/20 versus 14/20, P<0.001) and viral replication but did not improve weight gain. This model should be useful for further evaluations of the pathogenesis of CMV infections and for evaluation of antiviral drugs and vaccines. [Copyright &y& Elsevier]

In two recent clinical trials, a vaccine containing herpes simplex virus (HSV) type 2 glycoprotein D (gD2) and a novel adjuvant AS04 comprising alum (Al) and 3-deactylated monophosphoryl lipid A (3-dMPL) afforded HSV-seronegative women significant protection against HSV-2 genital disease (vaccine efficacy, 73% in study 1 and 74% in study 2) and limited protection against infection (46% in study 1 and 39% in study 2). In the present report, studies in the guinea pig model investigated the protection afforded by gD2/AS04 against HSV-1 and HSV-2 genital herpes and investigated whether immunization could prevent or reduce recurrent disease in guinea pigs that developed mucosal infection. Immunization with gD2/AS04 conveyed nearly complete protection against primary disease with either virus but did not prevent mucosal infection. Guinea pigs immunized with gD2/AS04 were significantly better protected against recurrent disease than were guinea pigs immunized with a gD2/Al vaccine, which suggests that inclusion of 3-dMPL improved protection against latent infection. [ABSTRACT FROM AUTHOR]

Abstract: The outcome of neonatal herpes simplex (HSV) infection, even after therapy with high dose acyclovir (ACV), is not optimum. We therefore evaluated N-Methanocarbathymidine ((N)-MCT) using the guinea pig model of neonatal herpes. Treatment with ACV (60mg/kg/day) was compared to doses of 1, 5, and 25mg/kg/day of (N)-MCT initiated 1, 2, or 3days postinoculation (dpi). Both ACV and (N)-MCT significantly improved survival, but only (N)-MCT significantly reduced the number of animals with symptoms when begun at 1dpi. When therapy was begun at 2dpi, only (N)-MCT (1, 5, or 25mg/kg/day) significantly increased survival. In fact, (N)-MCT improved survival up to 3dpi, the last time point evaluated. (N)-MCT was highly effective and superior to high dose ACV therapy for the treatment of neonatal herpes in the guinea pig model. [Copyright &y& Elsevier]

Genital herpes is a sexually transmitted disease representing a major global health concern. Currently, there is no approved vaccine and existing antiviral therapies exhibit limited efficacy. Herein, we describe an intranasal (IN) vaccine comprised of HSV-2 surface glycoproteins gD2 and gB2 formulated in a nanoemulsion adjuvant (NE01-gD2/gB2). Using the HSV-2 genital herpes guinea pig model, we demonstrate that IN NE01-gD2/gB2 induces higher levels of neutralizing antibody compared to a monovalent IN NE01-gD2 vaccine, but less than an intramuscular (IM) Alum/MPL-gD2 vaccine. Following intravaginal (IVag) challenge with HSV-2, the group immunized with IN NE01-gD2/gB2 exhibited significantly reduced acute and recurrent disease scores compared to placebo recipients. Significantly, latent virus was only detected in the dorsal root ganglia of 1 of 12 IN NE01-gD2/gB2-vaccinated animals compared to 11 of 12 placebo recipient. In the therapeutic model, IN NE01-gD2/gB2 immunized guinea pigs exhibited a significant reduction in the recurrent lesions scores (64%, p < 0.01), number of animal days with disease (64%, p < 0.01), number of animals with viral shedding (50%, p < 0.04) and reduction in virus positive vaginal swabs (56%, p < 0.04), These data suggests that the treatment may be effective in treating chronic disease and minimizing virus transmission. These results warrant advancing the development of IN NE01-gD2/gB2 as both a prophylactic and therapeutic vaccine against HSV-2. [ABSTRACT FROM AUTHOR]

Cross-neutralizing aptamers targeting both HSV-1 and HSV-2 were developed by selecting against the ectodomains of glycoprotein D (gD) from both viruses in parallel as well as sequentially using the SELEX method. Since gD facilitates viral invasion, sterically blocking the host-receptor interaction prevents infection. Candidate aptamers were screened, and lead aptamers were identified that exhibited exceptional neutralizing activity against both viruses in vitro. The specificity of the aptamers was confirmed by comparing their activity to scrambled versions of themselves. Modifications of the lead compounds were tested to define critical motifs to guide development. Stability of the aptamers was increased using phosphorothioate backbone linkages, and 2' methoxy substitutions of terminal and key internal bases. Aptamers were applied in a guinea pig vaginal HSV-2 infection model and found to reduce both the viral load of infected animals and the severity of the resulting disease. These results suggest that cross-neutralizing aptamers can be developed into on-demand antiviral interventions effective against both HSV-1 and HSV-2. • Cross-neutralizing anti-HSV-1 and 2 DNA aptamer development. • Nuclease-resistant stabilization. • In vivo efficacy in guinea pigs. [ABSTRACT FROM AUTHOR]

Herpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients. Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivation animal models (intravaginal guinea pig HSV-2 infection model and ocular mouse HSV-1 infection model) is presented. Intermittent therapy of infected animals with 4–7 cycles of IM-250 during latency silences subsequent recurrences analyzed up to 6 months. In contrast to common experience, our studies show that the latent reservoir is indeed accessible to antiviral therapy altering the latent viral reservoir such that reactivation frequency can be reduced significantly by prior IM-250 treatment. We provide evidence that antiviral treatment during HSV latency can reduce future reactivation from the latent reservoir, supporting a conceptual shift in the antiviral field, and reframing what is achievable with respect to therapy of latent neuronal HSV infections. • HPI IM-250 has sufficient exposure in the neuronal target tissue of HSV latency. • IM-250 therapy reduces future reactivation from the neuronal latent viral reservoir. • Potential conceptual shift in the treatment of neuronal HSV infections. • May be tested in Alzheimer's disease such as done with Valtrex (NCT04710030). • Phase 1 clinical trial with IM-250 has been approved and is currently ongoing. [ABSTRACT FROM AUTHOR]

Abstract: Genital herpes simplex virus (HSV) infections are common but results from vaccine trials with HSV-2 glycoprotein D (gD) have been disappointing. We therefore compared a similar HSV gD2 vaccine, to a further truncated gD2 vaccine, to a vaccine with gD2 plus gB2 and gH2/gL2 and to a vaccine with only gB2 and gH2/gL2 in a guinea pig model of genital herpes. All vaccines were administered with cationic liposome-DNA complexes (CLDC) as an adjuvant. All vaccines significantly decreased the severity of acute genital disease and vaginal virus replication compared to the placebo group. The majority of animals in all groups developed at least one episode of recurrent disease but the frequency of recurrent disease was significantly reduced by each vaccine compared to placebo. No vaccine was significantly more protective than gD2 alone for any of the parameters described above. No vaccine decreased recurrent virus shedding. When protection against acute infection of dorsal root ganglia and the spinal cord was evaluated all vaccines decreased the per cent of animal with detectable virus and the quantity of virus but again no vaccine was significantly more protective than another. Improvements in HSV-2 vaccines may require inclusion of more T cell targets, more potent adjuvants or live virus vaccines. [Copyright &y& Elsevier]

Abstract: Herpes simplex virus (HSV) infections are common but there is no vaccine available. We evaluated cationic liposome–DNA complexes (CLDC) as an adjuvant for an HSV gD2 vaccine and compared it to an MPL/Alum adjuvant in a guinea pig model of genital herpes. The addition of CLDC to the gD2 vaccine significantly decreased acute and recurrent disease and most importantly the number of days with recurrent virus shedding compared to gD2 alone. Reductions in these outcomes were also detected when gD2+CLDC was compared to gD2+MPL/Alum. When the vaccine and adjuvants were evaluated as therapeutic vaccines, they were ineffective. CLDC enhanced protection compared to MPL/Alum and is the first vaccine to reduce recurrent virus shedding, a key to decreasing the spread of HSV-2. [Copyright &y& Elsevier]

Abstract: A mouse model of recurrent herpes simplex type 2 (HSV-2) would improve our understanding of the immunobiology of recurrent disease and provide a useful model for evaluating antiviral treatments. We developed a model to evaluate recurrent vaginal HSV-2 shedding using high-dose acyclovir (ACV) therapy beginning at 3 days post infection (dpi). Treatment with 150mg/kg of ACV for 10 days increased survival to 80% following vaginal challenge with HSV-2 strain 186 and to 100% after challenge with strain MS. We then evaluated recurrent vaginal HSV-2 shedding in surviving mice. Although infectious virus was not detected in vaginal samples after 21dpi, viral DNA was detectable by PCR in 80% of mice (47/59) on at least 1 day, while no animal was positive for virus on every day. ACV therapy administered from day 21 to 31 significantly reduced recurrent virus shedding during this period from 7.3% (8/109 swabs) to 0.8% (1/126 swabs) (p =0.013). Lastly, ACV-rescued HSV-2-infected mice treated with cyclophosphamide at 35 and 38dpi rapidly succumbed, indicating that this model can be used to study immune control of the persistent infection. Thus, this model provides an inexpensive model for evaluating therapeutic strategies and immune control of persistent HSV. [Copyright &y& Elsevier]

Human cytomegalovirus (HCMV) is the most common cause of congenital viral infection in the developed world, and can lead to significant morbidity. Animal models of HCMV infection are required for study of pathogenesis, because of the strict species-specificity of cytomegalovirus (CMV). Among the small animal CMV models, the guinea pig CMV (GPCMV) has unique advantages, in particular its propensity to cross the placenta, causing disease in utero. In order to develop quantitative endpoints for vaccine and antiviral therapeutic studies in the GPCMV model, a quantitative-competitive PCR (qcPCR) assay was developed, based on the GPCMV homolog of the HCMV UL83 gene, GP83. Optimal amplification of GPCMV DNA was observed using primers spanning a 248 base pair (bp) region of this gene. A 91 bp deletion of this cloned fragment was generated for use as an internal standard (IS) for PCR amplification. Standard curves based upon the fluorescent intensity of full-length external target to IS were compared with signal intensity of DNA extracted from blood and organs of experimentally infected guinea pigs in order to quantify viral load. Viral load in newborn guinea pigs infected transplacentally was determined and compared with that of pups infected with GPCMV as neonates. Viral loads were highest in pups infected as neonates. The most consistent isolation and highest quantities of viral DNA were observed in liver and spleen, although viral genome could be readily identified in brain, lung, and salivary gland. Viral load determination should be useful for monitoring outcomes following vaccine studies, as well as responses to experimental antiviral agents. [Copyright &y& Elsevier]

Presents a study which used the guinea pig (gp) model of congenital cytomegalovirus (CMV) infection to evaluate a gpCMV glycoprotein vaccine. Materials and methods; Results; Discussion.

Infection with Herpes Simplex Viruses (HSVs) represents a significant health burden worldwide with HSV-1 and HSV-2 causing genital disease and HSV-2 contributing to human immunodeficiency virus acquisition. Despite great need, there is currently no licensed vaccine against HSV. In this report, we evaluated the protective efficacy of a vaccine containing highly purified, inactivated HSV-2 particles (with and without additional recombinant glycoprotein D) formulated with a monophosphoryl lipid A/Alhydrogel adjuvant in a guinea pig HSV genital model. The key results from 3 independent studies were: (1) vaccination consistently provided significant 3–3.5 Log10 reductions in vaginal HSV-2 titers on day 2 postchallenge; (2) following homologous or heterologous challenge with two U.S. isolates, all vaccine groups showed complete protection against lesion formation, significant 3 Log10 reductions in day 2 virus shedding, enhanced virus clearance, significant reductions in HSV-2 DNA within ganglia, and no detectable shedding (<2 PFU) or latent viral DNA in some immunized animals; (3) following challenge with a third heterologous strain, vaccination provided complete protection against primary and recurrent lesions, significant reductions in primary virus shedding, a 50% reduction in recurrent shedding days, and undetectable latent virus in the ganglia and spinal cords of most animals; and (4) adding glycoprotein D provided no enhanced protection relative to that elicited by the inactivated HSV-2 particles alone. Together, these data provide strong support for further development of this exceedingly protective and highly feasible vaccine candidate for human trials. [ABSTRACT FROM AUTHOR]

Background: Although herpes simplex viruses (HSV) are a major target for vaccine development no vaccine is currently licensed. Methods: A live attenuated HSV virus vaccine, VC2 was compared to a subunit HSV vaccine, glycoprotein D (gD2) administered with the adjuvant, MPL/Alum using the guinea pig model of genital herpes. Three doses of intramuscular (IM) vaccine were provided followed by intravaginal challenge with HSV-2 at either 3 weeks or six months after the last vaccination. Results: Both VC2 and gD2 vaccines reduced acute genital disease. VC2 was somewhat more effective in reducing acute vaginal replication, the amount of virus in neural tissue, subsequent recurrent disease and recurrent virus shedding following challenge at 3 weeks post vaccination. Both vaccines continued to provide protection at 6 months after vaccination but the differences between the vaccines became more pronounced in favor of the live attenuated vaccine, VC2. Significant differences in acute disease, acute vaginal virus replication, recurrent disease and recurrent virus shedding (P<0.05 for each) was observed comparing the vaccines. Re-examination of protection for this study using criteria similar to those used in recent clinical trials (inclusion of recurrent disease) showed that efficacy may not be as high in this model as previously thought prompting a need to assess the best predictive outcomes for protection in humans. Conclusion: While both the live attenuated vaccine, VC2, and the gD2 subunit vaccine provided protection, the duration of protection appeared to be greater for VC2. Using the same evaluation criteria as used in human trials provided unique insights into the utility of the guinea pig model. [ABSTRACT FROM AUTHOR]

Abstract Background Although development of an HSV vaccine is a priority there is currently no vaccine available. The recent failure of subunit vaccines suggest that presentation of more antigens via a live attenuated vaccine may be required for protection. We therefore evaluated VC2, a live attenuated HSV vaccine, engineered to be unable to enter into neuronal axons. Methods VC2 pathogenesis was first evaluated in guinea pigs following intravaginal inoculation. VC2 was then evaluated as a prophylactic and therapeutic vaccine and compared protection to a gD2 vaccine adjuvanted with MPL/Alum in the guinea pig model of genital HSV-2. The guinea pig model allows evaluation of acute and recurrent disease, as well as vaginal shedding acutely and during episodes of recurrent activation. Results VC2 was significantly attenuated in guinea pigs compared to the wild type strain, 17syn+. It replicated poorly at the inoculation site, did not produce any genital disease and rarely infected the neural tissue. After prophylactic vaccination, the VC2 vaccine decreased the clinical severity of acute and recurrent HSV-2 disease and shedding and decreased the quantity of virus in the DRGs. When compared to gD2+MPL/Alum, VC2 was somewhat more effective especially as it relates to neural tissue infection. VC2 was not effective as a therapeutic vaccine. Conclusion The live attenuated prophylactic HSV vaccine, VC2, was effective in the guinea pig model of genital HSV-2. Its decreased ability to infect neural tissues provides advantages over other live attenuated vaccines. [ABSTRACT FROM AUTHOR]

Immunotherapeutic herpes simplex virus 2 (HSV-2) vaccine efficacy depends upon the promotion of antigen-specific immune responses that inhibit reactivation or reactivated virus, thus controlling both recurrent lesions and viral shedding. In the present study, a candidate subunit vaccine, GEN-003/MM-2, was evaluated for its ability to induce a broad-spectrum immune response in mice and therapeutic efficacy in HSV-2-infected guinea pigs. GEN-003 is comprised of HSV-2 glycoprotein D2 (gD2ΔTMR340-363) and a truncated form of infected cell polypeptide 4 (ICP4383-766), formulated with Matrix M-2 (MM-2) adjuvant (GEN-003/MM-2). In addition to eliciting humoral immune responses, CD4+ and CD8+ T cells characterized by the secretion of multiple cyto-kines and cytolytic antigen-specific T cell responses that were able to be recalled at least 44 days after the last immunization were induced in immunized mice. Furthermore, vaccination with either GEN-003 or GEN-003/MM-2 led to significant reductions in both the prevalence and severity of lesions in HSV-2-infected guinea pigs compared to those of phosphate-buffered saline (PBS) control-vaccinated animals. While vaccination with MM-2 adjuvant alone decreased recurrent disease symptoms compared to the PBS control group, the difference was not statistically significant. Importantly, the frequency of recurrent viral shedding was considerably reduced in GEN-003/MM-2-vaccinated animals but not in GEN-003- or MM-2-vaccinated animals. These findings suggest a possible role for immunotherapeutic GEN-003/MM-2 vaccination as a viable alternative to chronic antiviral drugs in the treatment and control of genital herpes disease. [ABSTRACT FROM AUTHOR]

Glycoprotein B (gB) has emerged as a subunit-vaccine candidate for congenital cytomegalovirus (CMV) infection, a major public health problem. The present study evaluated a cloned, recombinant gB vaccine in the guinea pig cytomegalovirus (GPCMV) model of congenital infection. Guinea pigs were immunized with gB, which was coadministered with either Freund's adjuvant or alum. All gB-immunized dams had enzyme-linked immunosorbent-assay and neutralizing-antibody responses, with significantly higher titers in the gB/Freund's group. Pregnant dams were challenged with GPCMV subcutaneously during the 3rd trimester. Maternal DNAemia on day 10 after infection trended lower in gB-immunized dams than in control animals, with significant reductions in the gB/Freund's group. Vaccination resulted in a highly significant reduction in pup mortality. For the gB-vaccine groups, pup mortality was significantly lower, and reduced rates of GPCMV transmission were noted, for dams immunized with gB and Freund's adjuvant, compared with dams immunized with gB and alum. These are the first data indicating that a recombinant gB vaccine protects against congenital CMV infection and disease. [ABSTRACT FROM AUTHOR]