A matter of models

LONDON—A scientific collaboration between Envigo and the Department of Infectious Disease at the University of Gothenburg, Sweden, has unveiled study findings into rat models and their susceptibility to intravaginal herpes simplex virus-2 (HSV-2) infection. A synopsis of the study and its conclusions are outlined in a poster entitled “Novel rat models to study primary genital herpes simplex virus-2 infection.”

Sheryl Wildt, Envigo’s global manager of genetic quality and breeding, commented, “There is an urgent need for a vaccine against herpes simplex virus type-2 (HSV-2), not only because HSV-2 is a common sexually transmitted virus, but also because HSV-2 infection facilitates transmission of HIV. Limitations to HSV-2 genital mouse models and guinea pig models led us to investigate whether our Envigo rat stocks or strains were susceptible to HSV-2 infection and, if so, to determine if attenuated HSV-1 could serve as a protection against symptomatic HSV-2 infections in susceptible animals. To our knowledge, there are no previous studies describing rats as a genital model of HSV-2 infection.”

There are some limitations to using any mouse model for HSV-2 research, Wildt notes. “In mice, the genital mucosa is susceptible to HSV-2 infection only in diestrous phase. Synchronization of the mucosa therefore requires progesterone treatment before infection or challenge. Moreover, the mouse model cannot be used to study latency and spontaneous reactivation and genital shedding. Compared to mice, the rats represent a better model for replication of different stages of infection.”

The Envigo study demonstrated that several Envigo rat models are susceptible to genital HSV-2 infection, with the outcome varying between different stocks or strains. The F344/NHsd strain proved to be the most susceptible and may be suitable as an alternative or complementary animal model for efficacy studies for prophylactic vaccine candidates. The Hsd:Sprague Dawley SD stock, being the least susceptible, can be used to study protective immune mechanisms involved in the primary asymptomatic HSV-2 infection. This model also has the potential to recapitulate the human genital HSV-2 infection.

Furthermore, Envigo investigated if prior HSV-1 infection is protective against HSV-2 infection, and found that all HSV-2 infected rats previously infected with attenuated HSV-1 survived and developed no genital or systemic symptoms.

An attenuated virus is created by reducing the virulence of the virus, but still keeping it viable. Attenuation takes an infectious agent and alters it so that it becomes harmless or less virulent, but still retains properties that allow the immune system to mount a defense.

When asked if an attenuated HSV-1 virus might have potential as a vaccine against HSV-2 infection, Wildt responds cautiously. “Whether a prior genital HSV-1 infection can prevent or reduce clinical symptoms of a subsequent HSV-2 infection in humans is unclear, as there are no published studies yet available on this issue. By further studying the rat models identified in this research that are resistant, we can better understand the underlying mechanism which could lead to an improved vaccine candidate.”

Consequently, the described Envigo rat models provide a new approach to investigate the protective effects of antiviral microbiocides and vaccine candidates as well as to study asymptomatic primary genital HSV-2 infection.

Envigo provides essential research services, models and products for biopharmaceutical, crop protection and chemical companies as well as universities, governments and other research organizations. The company’s business is founded on a dedication to customer service and the expertise and experience of 3,800 people, and boasts more than 50 locations worldwide.