Clinical study results pave the way for a promising new approach to rotavirus vaccines

July 9, 2015 by PATH

Injected, non-replicating vaccines hold potential for expanded impact in developing countries

Data published this week in Vaccine reveal a promising immune response among adults who received a novel non-replicating rotavirus vaccine candidate. Rotavirus accounts for more than one-third of all childhood diarrhea deaths worldwide, and PATH is evaluating the potential of non-replicating rotavirus vaccines, or NRRVs, as valuable additions to the global vaccine portfolio.

Live, orally administered rotavirus vaccines have made a major public health impact since they were first licensed nearly a decade ago. However, as with other oral vaccines, their efficacy is lower in developing countries in comparison to high- and middle-income nations, highlighting the need to consider new approaches. Reduced efficacy may be due to elevated maternal antibodies, potential interference from other oral vaccines, malnutrition, and co-infections in a child's gut, among other issues. Inactivated vaccines like NRRVs, which are injected rather than orally administered, may circumvent some of these factors.

The Phase 1 clinical study, conducted at the Center for Immunization Research at the Johns Hopkins School of Public Health, evaluated the safety, reactogenicity, and tolerability of the P2-VP8 rotavirus vaccine candidate among healthy US adults not previously immunized against rotavirus. The study found the vaccine to be safe and to evoke a strong immune response. Study participants developed high levels of antibodies after immunization and also produced neutralizing antibodies against strains not included in the vaccine.

"Non-replicating rotavirus vaccines offer an exciting approach to preventing the most common cause of severe and deadly childhood diarrhea," said Dr. Stan Cryz, director of PATH's NRRV project. "These data are very promising, and further studies will help us investigate their potential to protect children worldwide." 

Rotavirus is the most common cause of severe childhood diarrhea and is particularly lethal in developing countries of Africa and Asia, where urgent medical care can be scarce or out of reach. The World Health Organization (WHO) recommends rotavirus vaccines be included in all national immunization programs, particularly in countries where diarrheal disease is a major health problem. Vaccination against rotavirus is the best way to prevent it, and rotavirus vaccines are an important part of a portfolio of interventions to prevent and treat all of diarrhea's causes. This portfolio should include rotavirus vaccines, as well as oral rehydration therapy, zinc, breastfeeding, improvements in water, sanitation, and hygiene, as well as proper nutrition.

PATH's NRRV project is working with partners to advance clinical development of promising candidates, including the P2-VP8 candidate, which was developed at the US National Institute of Allergy and Infectious Diseases. Building from these positive results among adults, PATH and the Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, based at the Chris Hani Baragwanath Academic Hospital in South Africa, are evaluating safety and immunogenicity of the P2-VP8 vaccine in toddlers and infants. Additionally, PATH is developing a trivalent formulation to potentially provide broader protection against the most prevalent rotavirus strains in Africa and Asia.

About Vaccine

Vaccine is the pre-eminent journal for those interested in vaccines and vaccination. It is the official journal of The Edward Jenner Society, The International Society for Vaccines and The Japanese Society for Vaccinology and is published by Elsevier.

Article reference

"Safety and immunogenicity of a parenterally administered rotavirus VP8 subunit vaccine in healthy adults," by Alan D. Fix, MD, Clayton Harro, MD, Monica McNeal, MS, Len Dally, MD, Jorge Flores, MD, George Robertson, PhD, John W. Boslego, PhD, and Stanley Cryz, PhD. DOI: It appears in Vaccine, Volume 33, Issue 31 (2015), published by Elsevier.

Copies are available to credentialed journalists upon request; please contact Elsevier's Newsroom at or +31 20 4853564.