Genital herpes simplex virus-2 (HSV-2) infections are a major public health problem affecting >40 million people in the United States and >500 million globally. HSV-2 infection causes recurring, genital sores that are painful and result in considerable psychological distress. Transmission can occur during sexual contact and from mother to child during birth with fatal consequences. There is no effective vaccine to prevent HSV-2. NanoBio Corporation is developing a novel, intranasal nanoemulsion (NE) vaccine that elicits serum neutralizing activity, a Th1 response, and Th17 cells for mucosal immunity, thereby offering protection systemically and at the site of HSV-2 entry through the mucosal surface. The proprietary oil-in-water NE has been shown to incorporate, deliver and adjuvant multiple different antigen types when administered by the intranasal route, thus enabling broad protection against both respiratory and sexually transmitted diseases. The NE adjuvant was formulated with protective gB2 and gD2 antigens for evaluation in the HSV-2 guinea pig challenge model. Data generated from two studies in this model demonstrated that: i. Intranasal immunization conferred favorable protection following HSV-2 challenge compared to intramuscular administration; ii. Robust protection was conferred even though intranasal immunization elicited lower serum antibody levels, indicating that additional mucosal immunity determinants are involved; iii. Incorporation of two glycoproteins, gB2 and gD2, into the NE vaccine was superior to gD2 antigen alone, a finding not observed with previous intramuscular vaccine candidates; and, iv. Intranasal immunization of the NE gB2/gD2 vaccine showed superior efficacy in the guinea pig model for prevention of infection, shedding, chronic recurrence, and viral latency, as compared to a conventional intramuscular gD2 vaccine formulated in alum and monophosphoryl lipid A (MPL). These data support the development of an intranasal NE gB2/gD2 vaccine to achieve protection against HSV- 2. In this Direct Phase II SBIR program, NanoBio will develop the research cell banks and the viral stock for production of gB2 and gD2 antigens, and develop upstream and downstream processes for antigen production, purification and scale-up to produce 10,000 vaccine doses (1 gram purified antigen). NanoBio simultaneously will develop the analytical methods required for final drug product release. A pre-IND meeting will be conducted with the FDA. After completion of this SBIR project, funding will be sought out to perform cGMP-compliant production of the vaccine, and an IND will be filed with the FDA to enable phase I/II clinical trials to assess safety, immunogenicity and preliminary efficacy of the NE vaccine to prevent HSV-2 infection in humans. A prophylactic NE gB2/gD2 genital herpes vaccine that induces both mucosal and systemic immunity will have great medical benefit in preventing HSV-2 infection in the United States and throughout the world.
Public Health Relevance Statement: Project Narrative Genital herpes is a sexually transmitted disease most commonly caused by herpes simplex virus-2 (HSV-2). The disease is widespread in both developed and underdeveloped countries and is a global health priority. Infections are life-long such that chronic recurrences facilitate the spread of the disease amongst sexual partners and from mother to child during birth with potentially fatal implications. Genital herpes also predisposes to an increased risk of HIV infection. Currently, there is no approved vaccine for HSV-2. Therefore, the proposed studies will develop a novel nanoemulsion-based bivalent intranasal vaccine using a combination of gB2 and gD2 antigens to prevent HSV-2 viral infection, recurrence and latency. Development of a safe, easy-to-administer and highly effective nanoemulsion-based mucosal vaccine would have great medical value for prevention of HSV-2 infection in the United States and worldwide.
Project Terms: Acute; Adjuvant; Affect; aluminum sulfate; analytical method; Antibodies; antigen processing; Antigens; Baculoviruses; base; Beds; Biological Sciences; Birth; Caliber; Cavia; cell bank; cell growth; Cell Line; Cells; Child; Chronic; Clinical; Clinical Trials; Collaborations; Country; Cyclic GMP; Data; design; Development; Disease; Dose; drug testing; Ensure; Enzyme-Linked Immunosorbent Assay; Evaluation; experimental study; Formulation; Funding; Future; gene cloning; gene synthesis; Genes; genital herpes; Genital system; global health; Glycoproteins; Goals; Harvest; Health Priorities; Height; High Pressure Liquid Chromatography; HIV Infections; Hour; Housing; Human; Human Herpesvirus 2; Immunity; Immunization; Immunodiffusion; immunogenicity; in vivo; Infection; Infection prevention; Insecta; Intramuscular; Life; Lipid A; manufacturing process; Medical; meetings; Methods; Modeling; Mothers; Mucosal Immunity; mucosal vaccine; nanoemulsion; novel; Oils; operation; Pain; paragon; Pharmaceutical Preparations; Phase; Phase I Clinical Trials; Plant Resins; Plasmids; pre-clinical; preclinical study; Preparation; prevent; Prevention; Process; Production; programs; prophylactic; protein expression; Proteins; psychological distress; Public Health; Qualifying; Recurrence; Research; respiratory; response; Risk; Route; Safety; scale up; Seeds; Serum; Sexual Partners; Sexually Transmitted Diseases; Side; Site; Small Business Innovation Research Grant; Sterility; Surface; Testing; Time; transmission process; United States; Universities; Vaccine Antigen; vaccine candidate; Vaccine Production; Vaccines; Viral; Virus Diseases; Virus Latency; Water; Western Blotting
