Rational Vaccines believes live-attenuated virus vaccine development is the right approach

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Rational Vaccines, a vaccine biotech firm based in Cambridge, Mass., points to the proven science of live-attenuated viruses in vaccine development as key to the company’s commitment to the development platform.

A live-attenuated virus is a weakened (attenuated) virus that is able to multiply within the host to a limited extent and engineered to be unable to cause any disease.

“The live-attenuated vaccine approach has led to some of the most successful and cost-effective disease interventions in worldwide medical history,” said RVx CEO Agustin Fernandez.

Rational attenuation of live viruses can produce very safe vaccines with practically no chance to cause disease. The smallpox, polio, measles, rubella, chicken pox, and rotavirus vaccines are all live-attenuated. Mass immunizations of the live-attenuated smallpox vaccine led to that disease being eradicated around the world in 1980. In 1961, the FDA approved a live-attenuated polio vaccine, ultimately leading to a 99% global reduction in polio by 2000 – the same year that measles was declared eradicated until vaccination gaps led to outbreaks beginning in 2017.

The first live-attenuated rubella (German measles) vaccine was introduced in 1961, with the U.S. declaring the country free of that disease by 2004. More recently, the live-attenuated chicken pox vaccine accounted for dramatically reduced death rates and hospitalizations associated with that disease compared to before the vaccine’s approved use in 1995. In 2006, the first attenuated live viral vaccines for rotaviruses were introduced, drastically reducing associated illnesses and hospitalizations in the U.S. and infant and child morbidity and mortality worldwide.

Using live viruses to combat serious diseases such as polio led to safety concerns; in fact, the first successfully demonstrated live-attenuated oral polio vaccine (1950) was never approved for use in the U.S. A decade later, the U.S. approved Dr. Albert Sabin’s weakened, safe variant oral polio vaccine, which became instrumental in eradicating the disease. For decades Sabin’s live version largely replaced the only other approved option in the U.S., which was Jonas Salk’s inactivated, injected polio vaccine that was approved in 1955, proving that live viral vaccines can be used safely and cost-effectively. Both vaccine variants are still used worldwide today.

In the past, scientists did not have the advanced molecular tools available today that allow for the rational attenuation of viruses. In addition, advances in whole genome sequencing have allowed for detailed genetic identification and manipulation of pathogens, thus enabling the rational design of safe and effective live-attenuated mutants.

Concerns about the use of live-attenuated vaccines to compromised or underdeveloped immune systems led to the development of subunit vaccines. Subunit vaccines typically composed of one or more proteins of the targeted pathogen could be easily produced. The hope was that when mixed with adjuvants that are prone to elicit strong immune responses against the pathogen, subunit vaccines could then produce adequate immune responses.

“Despite their benefits and safety, however, subunit vaccines frequently have limitations, especially against more complex pathogens and specifically latent viruses that remain in a ‘silent’ state within infected hosts. For example, mutant viruses may escape anti-protein targeted immune responses, and may not induce long-term memory immune responses that protect against infection over a long period of time. Also, the possibility exists that weak antibody responses may enhance susceptibility to infection instead of preventing it, as is the case with Dengue viral infections,” said, Dr. Konstantin Kousoulas, RvX Chief Scientific Consultant for Basic Sciences.

Rational vaccine development is the design and engineering of a vaccine that retains as many characteristics of the viral pathogen as possible, while ensuring maximum attenuation and safety. In addition, this designed vaccine approach aims to elicit robust innate immune responses leading to strong and long-lasting (memory) humoral and cellular responses, which protect against the targeted pathogen.

“We fully support the research recommendation of the World Health Organization in making vaccine development decisions based on the specific benefits of each vaccine type,” said Fernandez. “Our company views the live-attenuated virus and rational design approach as a pathway to our success.”

About Rational Vaccines

Rational Vaccines develops rationally engineered, live attenuated viral immunotherapeutic and prophylactic vaccine candidates, particularly focused on combating all diseases resulting from herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) infections. Led by our team of world-renowned scientists and closely following all regulatory guidelines, the company currently has seven vaccine candidates in the pipeline. We are confident our team and technology will revolutionize the treatment, prevention, and diagnosis of herpes and herpes-related diseases so we can bring hope and healing to a world ravaged by this deadly disease. Based in Cambridge, MA, Rational Vx is also joining the battle against COVID-19 with a serological assay currently in development, and a future COVID-19 vaccine planned. For more information go to https://rationalvaccines.com or email information@rationalvaccines.com.

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SOURCE Rational Vaccines

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