Rational Vaccines' RVX1001 Vaccine Candidate Protects Against HSV Ocular Infection in vivo

WOBURN, Mass. and OXFORD, England, Dec. 28, 2021 /PRNewswire/ -- Rational Vaccines, a company focused on revolutionizing the treatment and prevention of herpes simplex viruses (HSV) to eradicate all forms of herpectic disease, today announced preclinical research suggesting that the Company's herpes simplex virus type 1 (HSV-1) vaccine candidate can protect against herpetic keratitis (HK), a leading infectious cause of blindness in developed countries.

The research was conducted by a team of scientists from Louisiana State University (LSU) School of Veterinary Medicine led by Konstantin G. Kousoulas, PhD, professor of virology and biotechnology at LSU School of Veterinary Medicine, and vice president of scientific affairs at Rational Vaccines. The study, "Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδ T Cell Intracorneal Infiltration¹" was published in Frontiers in Immunology and can be accessed at: https://bit.ly/3phI4DV.

Dr. Kousoulas stated, "These data provide in vivo proof of concept for the prophylactic treatment of herpetic keratitis with our HSV-1 vaccine. We look forward to advancing RVx1001 toward the clinic, led by these exciting results, which provide new hope to eradicate one of the leading infectious causes of blindness around the world."

Results showed that RVX1001 administered prophylactically protected mice against lethal ocular HSV-1 challenge and the development of herpetic keratitis. Of note, study data showed that intramuscular vaccination of mice with RVX-1001 resulted in γδ (gamma delta) T cell enhanced accumulation and reduction of infiltration neutrophils that results in substantial reduction of HSV ocular immunopathogenesis. Of particular note, γδ T cells are a distinct group of T cells that straddle the innate and adaptive arms of the immune system and are involved in response to pathogens, and tumors.²

People with compromised immune systems are particularly impacted by herpes. Herpetic keratitis induced by herpes simplex virus type 1 (HSV-1) ocular infection is a leading infectious cause of blindness. It is widely considered to be an immune-mediated condition where uncontrolled inflammatory events continue to damage the cornea during and after the resolution of infection.³ It is estimated that 50-90 percent of the world population is infected with HSV-1. ^4-6

"HSV-1 is a heinous virus that mostly infects the world's children. It is not only one of the leading infectious causes of blindness in the developed world, it is now also responsible for nearly 40 percent of all new genital herpes infections as well," said Rational Vaccines' CEO Agustin Fernandez. "There are several studies showing links of HSV-1 infection with cognitive decline in infected individuals. We are proud of our work in advancing this candidate from Dr. Kousoulas as our HSV-1 prophylactic vaccine, as we work toward one day eradicating the herpes virus"

In addition to Dr. Kousoulas, study co-authors included Rafiq Nabi, PhD, post-doctoral fellow, Therese M. Collantes, PhD, assistant professor, and Vladimir N. Chouljenko, PhD, research assistant professor, Department of Pathological Science, and Andrew C. Lewin, PhD, BVM&S, MRCVS, DACVO, assistant professor, Department of Veterinary Clinical Sciences.

About Herpes Simplex Virus (HSV)
The herpes simplex virus (HSV), commonly referred to as herpes, is categorized into two types: herpes simplex virus type 1 (HSV-1) and herpes simplex virus type 2 (HSV-2). HSV-1 is the primary cause of oral herpes but can also cause genital herpes. HSV-2 is the primary cause of genital herpes. According to a 2020 report by the World Health Organization (WHO), herpes infects billions globally – about a half a billion people worldwide are living with genital herpes, and several billions have oral herpes infection. Both HSV-1 and HSV-2 infections are lifelong.

While most herpes infections are asymptomatic, a significant number of people experience a range of symptoms that vary in frequency and severity. The most common symptoms for both types of herpes are painful blisters or ulcers. In addition, many patients experience debilitating neuralgia, skin splits, fissures, minor abrasions, erythema, fever, chills, and myalgias. Both viruses are most contagious during a symptomatic outbreak, but they can still be transmitted in the absence of symptoms. Beyond physical symptoms, herpes patients often suffer from social stigma and isolation because the infection is often transmitted sexually. Strong evidence has emerged that HSV-1 is a major risk factor for Alzheimer's Disease.

There is no cure for herpes. There are no approved vaccines or immunotherapies or sufficiently reliable diagnostics currently available⁴. Antiviral medications developed in the 1970s can help to reduce the severity and frequency of symptoms but cannot cure the infection.

About Rational Vaccines
Rational Vaccines is revolutionizing the treatment, prevention, and diagnosis of herpes and herpes-related diseases with its rationally engineered, live-attenuated viral immunotherapeutic and prophylactic vaccine candidates. Led by a team of world-renowned scientists, the Company is headquartered in Woburn, MA, with offices in Oxford, UK. For more information, please visit www.rationalvaccines.com.

1. Nabi R, Lewin AC, Collantes TM, Chouljenko VN, Kousoulas KG. Intramuscular Vaccination With the HSV-1(VC2) Live-Attenuated Vaccine Strain Confers Protection Against Viral Ocular Immunopathogenesis Associated With γδ T Cell Intracorneal Infiltration. Front. Immunol. (2021), 15 November 2021, 12:4742. doi: 10.3389/fimmu.2021.789454   
2. Pistoia V, Tumino N, Vacca P, Veneziani I, Moretta A, Locatelli F, Moretta L. Front. Immunol., 07 May 2018 https://doi.org/10.3389/fimmu.2018.00984  
3. Rowe AM, St Leger AJ, Jeon S, Dhaliwal DK, Knickelbein JE, Hendricks RL. Herpes Keratitis. Prog Retin Eye Res (2013) 32:88–101. doi: 10.1016/j.preteyeres.2012.08.002
4. Smith JS, Robinson NJ. Age-Specific Prevalence of Infection With Herpes Simplex Virus Types 2 and 1: A Global Review. J Infect Dis (2002) 186(Suppl 1):S3–28. doi: 10.1086/343739
5. Bradley H, Markowitz LE, Gibson T, McQuillan GM. Seroprevalence of Herpes Simplex Virus Types 1 and 2–United States, 1999-2010. J Infect Dis (2014) 209(3):325–33. doi: 10.1093/infdis/jit458
6. Kasubi MJ, Nilsen A, Marsden HS, Bergstrom T, Langeland N, Haarr L. Prevalence of Antibodies Against Herpes Simplex Virus Types 1 and 2 in Children and Young People in an Urban Region in Tanzania. J Clin Microbiol (2006) 44(8):2801–7. doi: 10.1128/JCM.00180-06

SOURCE Rational Vaccines