RSV Pediatric Vaccine Candidate Shows Promise in Early Clinical Trial

November 5, 2015

Scientists from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and colleagues at the Johns Hopkins Bloomberg School of Public Health and MedImmune, LLC, have developed a vaccine candidate to protect infants and young children against respiratory syncytial virus (RSV) that appears to elicit a stronger protective immune response than the previous lead vaccine candidate. RSV is the most common cause of lower respiratory tract infections—including pneumonia and bronchiolitis—among young children worldwide, according to the Centers for Disease Control and Prevention. Each year in the United States, RSV leads to an average of about 55,000 hospitalizations among children younger than 5 years, with most hospitalizations occurring among infants younger than 6 months. There is currently no approved vaccine to prevent RSV infection.

Previously the investigators at NIAID showed that deleting the M2-2 gene from RSV attenuates, or weakens, the virus so that it replicates inefficiently and does not cause disease but still produces high levels of viral antigens, which potentially could enhance the body’s immune response when given as a vaccine. To test this theory, investigators at Johns Hopkins conducted a Phase 1 clinical trial of a live intranasal vaccine candidate, called RSV MEDI ΔM2-2, made from this weakened version of RSV. The vaccine candidate was administered to a group of adults followed by a group of children, all of whom had previously had an RSV infection (RSV-seropositive). After determining the vaccine was safe in these populations, the scientists then gave the vaccine to 20 young children who had never had an RSV infection (RSV-seronegative). Ten RSV-seronegative children were also randomly selected to receive a placebo vaccine.

When compared with results from the previous leading live-attenuated RSV vaccine candidate, the RSV MEDI ΔM2-2 produced less virus and induced significantly higher levels of neutralizing antibodies in the RSV-seronegative children. The investigators monitored the children during the subsequent fall and winter, when RSV infection is most common, and found substantial increases in antibody levels among five of the 20 vaccinees without reporting any illnesses, suggesting that the vaccine provided protective immunity to RSV. Additional studies are ongoing, and the experimental vaccine may advance to an expanded Phase 1 trial.

ARTICLE: R Karron et al. A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children. Science Translational Medicine DOI: 10.1126/scitranslmed.aac8463 (2015)

WHO: Peter Collins, Ph.D., chief, and Ursula Buchholz, Ph.D., associate scientist, both of the RNA Viruses Section in the NIAID Laboratory of Infectious Diseases, are available to comment on this research.

Content last reviewed on November 5, 2015