This article is more than 5 years old. Information may no longer be current.
RSV vaccine development theory includes three approaches to treatment
Click Here to Manage Email Alerts
NEW YORK — Revolutionary developments toward respiratory syncytial virus prevention and vaccination plans, such as inhibiting RNA, targeting the RSV-F protein and blocking polymerase, are currently undergoing clinical testing, according to a presentation at the 2016 Infectious Diseases in Children Symposium.
These three approaches to treatment and prevention for RSV were hypothesized from laboratory analysis with replicating RSV cells by injecting the virus into healthy nasal cells, Octavio Ramilo, MD, the Henry G. Cramblett Chair in Infectious Diseases at The Ohio State University College of Medicine and pediatric expert at Nationwide Children’s Hospital, said.
“There are 53 RSV vaccines in the works,” she said. “Analyzing the two RSV proteins G and F are very important to monitor viral attachment to cells. The RSV-G protein allows the virus to attach to the respiratory cells, and the F-protein makes the fusion possible, the sycasia, that we see when we look at the virus cultures. The F-protein is very well-conserved, and as such makes a very good target for therapies, for antivirus, for antibodies and for vaccines.
“Subsequently, blocking the polymerase disallows fusion from occurring, and inhibits communication from the virus to healthy cells.”
The first approach to vaccine development for RSV is a very small interfering injection of RNA that interferes with the mechanism of the virus. Anti-RSV neutralizing monoclonal antibodies with combined palivizumab and motavizumab therapies interfere with RNA to block the mechanism of RSV to cell antibodies. Anti-RSV nanobody ALX-0171 binds the RSV-F antigenic site and in a phase 1/2a study in infants, ALX-0171 improved time to undetectable virus in culture compared with palivizumab.
In addition, a second RSV-F protein inhibitor, MEDI8897 (AstraZeneca), demonstrated potency that was 150 times greater compared with palivizumab in a separate study, Ramilo said.
Further, antiviral fusion inhibitor GS-5806 and nucleotide ALS-008176 have yielded effective viral load reductions in healthy adult volunteers with an approach that disconnects polymerase communication.
A vaccine for RSV would be an important step toward decreasing infant mortality and comorbidities worldwide. RSV infects and kills more children in their first 28 to 364 days of life on the global level than any other pathogen save malaria.
“In terms of the global RSV disease burden, when many different countries were analyzed for child death rates in the first year of life, malaria is number one, and RSV is number two,” Ramilo said. “RSV not only causes a lot of colds, bronchiolitis, hospitalizations, it is the number one cause of hospitalizations in the U.S., but under global analysis causes significant mortality.”
Phase 2 trials are also being performed via maternal immunization and infants postpartum to test the safety and efficacy in antibody microneutralization of an RSV-F nanoparticle vaccine. The new vaccine may be administered perinatally, rather than to the infant postpartum, and the effects of the immunization would spread to the offspring through the placenta and later through breastfeeding. – by Kate Sherrer
Reference:
Ramilo O. “Respiratory syncytial virus: on the verge of both prevention and treatment”. Presented at: IDC NY; Nov. 19-20, 2016; New York.
Disclosure: Ramilo reports consulting for AbbVie, Humabs BioMed, Janssen, Medimmune and Regeneron; and receiving research grants from NIH, NIAID, NICHD and Janssen.