Inactivated HSV-2 in MPL/alum adjuvant provides nearly complete protection against genital infection and shedding following long term challenge and rechallenge

Herpes Simplex Virus Type 2 (HSV-2) infection can result in life-long recurrent genital disease, asymptomatic virus shedding, and transmission. No vaccine to date has shown significant protection clinically. Here, we used a mouse model of genital HSV-2 infection to test the efficacy of a vaccine consisting of whole, formalin-inactivated HSV-2 (FI-HSV2) formulated with monophosphoryl lipid A (MPL) and alum adjuvants. Vaccine components were administered alone or as a prime-boost immunization together with DNA vaccines encoding a truncated glycoprotein D2 (gD2t) and two conserved HSV-2 genes necessary for virus replication, UL5 (DNA helicase) and UL30 (DNA polymerase). Our results show: (1) compared with mock immunized controls, mice immunized with FI-HSV2 plus MPL/alum consistently showed protection against disease burden and total viral shedding while the mice immunized with gD2t protein with MPL/alum did not; (2) protection against genital disease and viral replication correlated with the type of boost in a prime-boost immunization with little advantage afforded by a DNA prime; (3) intramuscular (i.m.) immunization with FI-HSV2 in MPL/Alhydrogel adjuvant provided nearly complete protection against vaginal HSV-2 shedding after a lethal intravaginal (i.vag.) short-term challenge and long-term rechallenge; (4) single formulation immunization with DNA vaccines, FI-HSV2, and MPL in an aluminum phosphate (Adju-Phos) adjuvant did not increase protection relative to FI-HSV2/MPL/Adju-Phos alone; and (5) addition of MPL/alum to the FI-HSV2 was required for optimal protection against disease, viral replication, and latent virus load in the dorsal root ganglia (DRG). Most notably, an optimized vaccine formulation of FI-HSV2 MPL/Alhydrogel given i.m. completely protected against detectable vaginal HSV-2 shedding in the majority of animals and HSV-2 latent DNA in the DRG of all animals.     

Cross protective efficacy of the Non-Neurotropic live attenuated herpes simplex virus type 1 vaccine VC-2 is enhanced by intradermal vaccination and deletion of glycoprotein G

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.     

Effects of herpes simplex virus type 2 glycoprotein vaccines and CLDC adjuvant on genital herpes infection in the guinea pig

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.     

A Vaxfectin-adjuvanted HSV-2 plasmid DNA vaccine is effective for prophylactic and therapeutic use in the guinea pig model of genital herpes

Here we describe studies in the guinea pig model of genital herpes to evaluate a novel plasmid DNA (pDNA) vaccine encoding the HSV-2 glycoprotein D and UL46 and UL47 genes encoding tegument proteins VP11/12 and VP 13/14 (gD2/UL46/UL47), formulated with a cationic lipid-based adjuvant Vaxfectin^®. Prophylactic immunization with Vaxfectin^®-gD2/UL46/UL47 significantly reduced viral replication in the genital tract, provided complete protection against both primary and recurrent genital skin disease following intravaginal HSV-2 challenge, and significantly reduced latent HSV-2 DNA in the dorsal root ganglia compared to controls. We also examined the impact of therapeutic immunization of HSV-2 infected animals. Here, Vaxfectin^®-gD2/UL46/UL47 immunization significantly reduced both the frequency of recurrent disease and viral shedding into the genital tract compared to controls. This novel adjuvanted pDNA vaccine has demonstrated both prophylactic and therapeutic efficacy in the guinea pig model of genital herpes and warrants further development.     

Effect of route of vaccination with vaccinia virus expressing HSV-2 glycoprotein D on protection from genital HSV-2 infection

To evaluate the effects of the route of vaccination on protection against genital HSV infection guinea pigs were vaccinated twice with vaccinia recombinants expressing HSV-2 glycoprotein D or controls by intradermal, intranasal or intravaginal inoculation. Following HSV-2 intravaginal challenge, immunization by all 3 routes reduced vaginal HSV shedding and acute genital disease. The intravaginal vaccination, however, most effectively reduced primary and recurrent HSV disease. Vaccinia and HSV antibody titers were similar in all vaccinia gD immunized groups while the lymphoproliferative response was highest in the intradermal group. In a smaller follow-up experiment we demonstrated that intrarectal immunization with vaccinia gD could also induce antibody and T cell responses.     

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.     

Effect of immunization with herpes simplex virus type-1 (HSV-1) glycoprotein D (gD) plus the immune enhancer GPI-0100 on infection with HSV-1 or HSV-2

These studies were performed to determine the effects of GPI-0100, a semi synthetic Quillaja Saponin analog, formulated with herpes simplex virus type-1 (HSV-1) glycoprotein D (gD) on immunity to HSV. SKH-1 hairless mice, used as a model of herpes labialis, inoculated with HSV-1 results in facial lesions, virus replication and mortality. Mortality rates, lesion scores and viral titers were significantly reduced in SKH-1 mice immunized with gD/GPI-0100 prior to cutaneous inoculation with HSV-1 and the protective effects were greater than those using the standard alum adjuvant. Genital HSV-2 infections in guinea pigs were also utilized to determine if gD combined with GPI-0100 was protective against infection, disease severity and viral shedding. Guinea pigs immunized with HSV-1 gD with or without GPI-0100 had significantly reduced area under the curve lesion scores, but infection rates and virus shedding was not altered. When Tween 40 was added to gD and GPI-0100, mean peak lesion scores were also significantly reduced. The results obtained in a genital HSV-2 infection of guinea pigs did not indicate enhanced protection or reduced virus shedding following immunization with GPI-0100 and gD. There was, however, a significant improvement in clinical herpetic genital disease with the combination of gD plus the immune enhancer GPI-0100.     

Poly I:C adjuvanted inactivated swine influenza vaccine induces heterologous protective immunity in pigs

Swine influenza is widely prevalent in swine herds in North America and Europe causing enormous economic losses and a public health threat. Pigs can be infected by both avian and mammalian influenza viruses and are sources of generation of reassortant influenza viruses capable of causing pandemics in humans. Current commercial vaccines provide satisfactory immunity against homologous viruses; however, protection against heterologous viruses is not adequate. In this study, we evaluated the protective efficacy of an intranasal Poly I:C adjuvanted UV inactivated bivalent swine influenza vaccine consisting of Swine/OH/24366/07 H1N1 and Swine/CO/99 H3N2, referred as PAV, in maternal antibody positive pigs against an antigenic variant and a heterologous swine influenza virus challenge. Groups of three-week-old commercial-grade pigs were immunized intranasally with PAV or a commercial vaccine (CV) twice at 2 weeks intervals. Three weeks after the second immunization, pigs were challenged with the antigenic variant Swine/MN/08 H1N1 (MN08) and the heterologous Swine/NC/10 H1N2 (NC10) influenza virus. Antibodies in serum and respiratory tract, lung lesions, virus shedding in nasal secretions and virus load in lungs were assessed. Intranasal administration of PAV induced challenge viruses specific-hemagglutination inhibition- and IgG antibodies in the serum and IgA and IgG antibodies in the respiratory tract. Importantly, intranasal administration of PAV provided protection against the antigenic variant MN08 and the heterologous NC10 swine influenza viruses as evidenced by significant reductions in lung virus load, gross lung lesions and significantly reduced shedding of challenge viruses in nasal secretions. These results indicate that Poly I:C or its homologues may be effective as vaccine adjuvants capable of generating cross-protective immunity against antigenic variants/heterologous swine influenza viruses in pigs.     

Native herpes simplex virus glycoprotein D vaccine: immunogenicity and protection in animal models.

Mice, guinea pigs, and rhesus monkeys were immunized with immunoaffinity-purified native glycoprotein D (gD) derived from herpes simplex virus type 1 (HSV1). The native glycoprotein has evoked significant in vivo responses even at low doses. Thus, mice immunized with doses as low as 1 microgram were significantly protected from the morbidity and mortality of lethal HSV2 challenge and from establishment of latent HSV2 infection. Protection was dose-related and correlated with prechallenge serum neutralizing antibody titres to HSV. Similarly, immunized guinea-pigs demonstrated significant reductions in the frequency, severity and duration of genital lesions induced by HSV2 vaginal challenge. In long term immunogenicity studies, immunized rhesus monkeys exhibited significant serum neutralizing antibody responses to both HSV1 and HSV2. In vitro stimulation of monkey peripheral blood leucocytes with purified gD resulted in a significant cellular proliferative response. The results obtained in these animal models with a gD subunit vaccine provide an appropriate foundation for the initiation of human studies.     

The HSV-1 live attenuated VC2 vaccine provides protection against HSV-2 genital infection in the guinea pig model of genital herpes

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.

Status of vaccine research and development of vaccines for herpes simplex virus

Herpes simplex virus type-1 (HSV-1) and -2 (HSV-2) are highly prevalent global pathogens which commonly cause recurrent oral and genital ulcerations. Less common but more serious complications include meningitis, encephalitis, neonatal infection, and keratitis. HSV-2 infection is a significant driver of the HIV epidemic, increasing the risk of HIV acquisition 3 fold. As current control strategies for genital HSV-2 infection, including antiviral therapy and condom use, are only partially effective, vaccines will be required to reduce infection. Both preventive and therapeutic vaccines for HSV-2 are being pursued and are in various stages of development. We will provide an overview of efforts to develop HSV-2 vaccines, including a discussion of the clinical need for an HSV vaccine, and status of research and development with an emphasis on recent insights from trials of vaccine candidates in clinical testing. In addition, we will touch upon aspects of HSV vaccine development relevant to low and middle income countries.     

Immunologic evaluation of 10 different adjuvants for use in vaccines for chickens against highly pathogenic avian influenza virus

Avian influenza viruses (AIV) are a threat to poultry production worldwide. Vaccination is utilized as a component of control programs for both high pathogenicity (HP) and low pathogenicity (LP) AIV. Over 95% of all AIV vaccine used in poultry are inactivated, adjuvanted products. To identify the best formulations for chickens, vaccines were prepared with beta-propiolactone (BPL) inactivated A/British Columbia/314514-1/2004 H7N3 LP AIV using ten commercially available or experimental adjuvants. Each vaccine formulation was evaluated for immunogenicity in chickens. Challenge studies with an antigenically homologous strain of HPAIV were conducted to compare protection against mortality and measure reductions in virus levels in oral swabs. The four best adjuvants from the studies with BPL inactivated antigen were selected and tested identically, but with vaccines prepared from formalin inactivated virus. Mineral and vegetable oil based adjuvants generally induced the highest antibody titers with 100% seroconversion by 3 weeks post vaccination. Chitosan induced positive antibody titers in 100% of the chickens, but the titers were significantly lower than those of most of the oil based adjuvants. Antibody levels from calcium phosphate and alginate adjuvanted groups were similar to those of non-adjuvanted virus. All groups that received adjuvanted vaccines induced similar levels of protection against mortality (0–20%) except the groups vaccinated with calcium phosphate adjuvanted vaccines, where mortality was similar (70%) to groups that received non-adjuvanted inactivated virus or no vaccine (60–100% mortality). Virus shedding in oral swabs was variable among the treatment groups. Formalin inactivated vaccine induced similar antibody titers and protection against challenge compared to BPL inactivated vaccine groups. These studies support the use of oil adjuvanted vaccines for use in the poultry industry for control for AIV.     

Therapeutic HSV-2 vaccine decreases recurrent virus shedding and recurrent genital herpes disease

BackgroundGenital herpes simplex virus (HSV) type 2 is a common persistent infection that frequently reactivates to cause recurrent lesions and recurrent viral shedding which is incompletely controlled by antiviral therapy. GEN-003 is a candidate therapeutic vaccine containing 2 HSV-2 proteins, gD2 and ICP4, and Matrix-M2 adjuvant (M2).MethodsHSV-2 seropositive persons with genital herpes were randomized into three dose cohorts of Gen-003 (60 µg antigen/50 µg M2, 60 µg/75 µg M2 or Placebo). Three intramuscular doses 21 days apart of GEN-003 or placebo were administered. Participants obtained genital area swabs twice-daily for HSV-2 detection and monitored genital lesions for 12 months. The rates of virus shedding and lesion rates before vaccination were compared to 3 defined periods after vaccination; Days 43–71, Month 6 and Month 12.ResultsGEN-003 at a dose of 60 µg each antigen/50 µg M2 reduced HSV shedding immediately after dosing with a rate ratio of 0.58, compared to 0.75 for the GEN-003 60 µg/75 µg M2 and 1.06 for placebo. Lesion rates, recurrence rates, and duration of recurrences were also reduced. Reactogenicity was higher with the 75 µg M2 dose than the 50 µg M2 dose, specifically for pain, tenderness, malaise and fatigue. Antibody and cellular immune responses were stimulated by both doses and persisted to 12 months.ConclusionsGEN-003 vaccine manufactured with a scalable process gave results similar to those observed in prior clinical trials. GEN-003 had an acceptable safety profile and stimulated both humoral and cellular immune responses. The 60 µg antigen/50 µg M2 provided the maximal effect on virologic and clinical measures and warrants further development. (Funded by Genocea; ClinicalTrials.gov number NCT02515175).     

Comparison of immune responses after intra-typic heterologous and homologous vaccination against foot-and-mouth disease virus infection in pigs

This study compares the immune responses and protection induced by intra-typic heterologous vaccination with that induced by homologous vaccination against challenge with foot-and-mouth disease virus (FMDV). Humoral and cell-mediated immune responses and protection against challenge with FMDV O Taiwan were examined in a non-vaccinated group, a group vaccinated with O Taiwan FMD vaccine and a group vaccinated with O Manisa FMD vaccine. Five pigs from each group were challenged with FMDV type O Taiwan 14 days after vaccination and five other pigs were contact-exposed to the inoculated pigs. Both homologous and heterologous vaccination protected against challenge with FMDV O Taiwan at 2 weeks after vaccination. In the heterologous vaccinated group, cross-neutralizing antibody titres against O Taiwan could be detected although the ratio 'r(1)' was 0.4, which was significantly smaller than the critical r-value. Cell-mediated immune responses were detected after both homologous and heterologous vaccination. Virus-induced in vitro lymphocyte (cross-) proliferation and production of both a Th1-type (IFN-gamma) and a Th2-type (IL-10) cytokine response were demonstrated in cultures of peripheral blood mononuclear cells (PBMC). The findings show that heterologous (emergency) vaccination can prevent clinical disease and shedding of virus. The induction of the cell-mediated immune responses after (heterologous) vaccination needs more research but data on these responses might provide additional tools for both vaccine choice and vaccine development.     

Reinfections and site-specific immunity in herpes simplex virus infections

Studies with human volunteers and patients suffering from recurrent herpes simplex virus (HSV) infections have shown that reinfections with autologous or heterologous strains, occurring at sites distant from those of the recurrences, are possible in a variable proportion of the subjects. Experiments in animals have shown that mice surviving a primary HSV infection in the lumbo-sacral area, can become latently infected in trigeminal ganglia upon reinfection of the orofacial site. Similar results were obtained after vaccination of mice with a thymidine-kinase negative, non-pathogenic HSV-1 mutant. It was also demonstrated that initial HSV-1 eye infection in rabbits prevents superinfection of trigeminal ganglia by other strains.     

A mucosal vaccination approach for herpes simplex virus type 2

An estimated 1 out of every 5 Americans is infected with herpes simplex virus type 2 (HSV-2). Efforts in developing a potent vaccine for HSV-2 have shown limited success. Here we describe a heterologous vaccination strategy for HSV-2 based on an intramuscular DNA prime followed by a liposome-encapsulated antigen boost delivered intranasally. Both portions of the vaccine express the immunogenic HSV-2 glycoprotein D. In female Balb/c mice, this heterologous immunisation regimen stimulated high titers of serum neutralising antibodies, a DNA priming dose dependent T helper type response, enhanced mucosal immune responses and potent protective immunity at the portal of entry for the virus: the vaginal cavity. A clear synergistic effect on immune responses and protection from infection was seen using this heterologous immunisation approach. Suboptimal DNA prime (0.5 μg) followed by the liposome boost resulted in an 80% survival rate when mice were infected 2 weeks after immunisation. A higher dose of DNA priming (5 μg) followed by the liposome boost resulted in sterilising immunity in 80% of mice. The vaccine induced durable protection in mice, demonstrated by a 60% survival rate when lethal infections were performed 20 weeks after the immunisation primed with 0.5 μg of DNA vaccine.     

Intranasal nanoemulsion-adjuvanted HSV-2 subunit vaccine is effective as a prophylactic and therapeutic vaccine using the guinea pig model of genital herpes

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.     

A truncated glycoprotein G vaccine formulated with Advax-CpG adjuvant provides protection of mice against genital herpes simplex virus 2 infection

Herpes simplex virus type 2 (HSV-2) is a common sexually transmitted disease that affects approximately 500 million individuals globally. There is currently no approved vaccine to prevent HSV-2 infection. EXCT4 is a truncated form of the mature glycoprotein G-2 (mgG-2) that unlike full mature form is secreted by expressing cells enabling it to be rapidly scaled up for production. The current study examined whether EXCT4 immunity in mice could be further enhanced through use of adjuvants. EXCT4 formulated with Advax-CpG adjuvant induced a strong Th1-type immune response characterized by interferon gamma (IFN-γ) and protected animals against a lethal genital challenge with HSV-2. This response was associated with reduced viral load in vaginal washes, spinal cord, and dorsal root ganglia. Together the results provide proof of concept that EXCT4 formulated with Advax-CpG adjuvant is a promising HSV-2 vaccine candidate warranting further investigation.     

Live attenuated rabies virus co-infected with street rabies virus protects animals against rabies

While current rabies post-exposure prophylaxis (PEP) is highly effective, it is costly and the vaccination regimen is complicated, requiring both inactivated vaccines and immunoglobulins. A one-dose rabies vaccine for human PEP remains a long-term goal. Here, we describe development of a highly attenuated rabies virus ERAg3m, with a mutation in the glycoprotein (G) gene and a switch of the G gene with the matrix protein gene in the viral genome. After a one-dose intramuscular vaccination, the ERAg3m virus protected 100% of mice and hamsters from lethal challenge. In co-infections, using a lethal dose of street rabies virus mixed with ERAg3m, 100% of hamsters and 90% of mice survived and were protected against subsequent infection. A mock co-infection, using inactivated commercial human rabies vaccine and a lethal dose of street rabies virus, protected 100% and 40% of hamsters and mice, respectively. In co-infections, when vaccine was administrated in the left leg and challenge virus in the right leg, the ERAg3m virus protected 40% of mice, while the inactivated vaccine showed no protection. Therefore, live attenuated rabies virus when given pre-exposure or co-infected with street rabies virus, is capable of preventing rabies in two different animal models. Overall, this highly attenuated live rabies virus offered better protection than the inactivated vaccine.     

The adjuvant CLDC increases protection of a herpes simplex type 2 glycoprotein D vaccine in guinea pigs

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.