ATLANTA – A new vaccine for respiratory syncytial virus may truly be on the horizon, given recent advances in basic science and a marked increase in interest in the pharmaceutical industry.
That’s the conclusion of Larry Anderson, MD, professor of infectious disease in the Emory University department of pediatrics, who presented the most updated research and progress on a respiratory syncytial virus (RSV) vaccine during a conference sponsored by the Centers for Disease Control and Prevention.
©Dr. Craig Lyerla/CDC
This is the photomicrographic detection of respiratory syncytial virus (RSV) using indirect immunofluorescence technique.
The high hospitalization rates of infants with RSV, also associated with later development of reactive airway disease and asthma, highlight the challenge of developing a vaccine, Dr. Anderson said.
“The infant has an immature immune system less able to respond vigorously to a vaccine,” he said. “Also, it is highly susceptible to the disease of RSV, and therefore safety becomes an issue at least in terms of the live virus vaccine.” Furthermore, RSV causes multiple repeat infections throughout life, “which underlines the difficulty in inducing a protective immune response,” he added.
But Dr. Anderson said he believes there is light at the end of the tunnel when it comes to a vaccine for the virus.
“I think in terms of [the] potential of having an RSV vaccine in the near future, now is the most promising time, recognizing that work on an RSV vaccine has been going on for over 50 years without success to date,” he said. Significant advances in basic biology, immunology, and vaccinology have led to a better understanding of the virus, and new tools such as reverse genetics make “it possible to make any live virus you want as long as you know what you want,” he added.
Dr. Anderson provided an overview of published and preliminary data on the progress of more than five dozen groups working on an RSV vaccine. About 70% of these candidates remain in preclinical research, primarily in animal models. Of the dozen in phase I, several look promising, he said. Another six vaccines are in phase II or phase III testing, and MedImmune’s Synagis is market approved. But not all target infants.
“The first and highest priority is the young infant, particularly the under 2- to 4-month-old,” he said. In infants aged 4-6 months, it’s likely easier to induce an immune response, and there’s less susceptibility to disease with replication of the virus, he said. The elderly, also at high risk for RSV, would be another target population.
Potentially “the lowest apple on the tree for immunization,” Dr. Anderson said, would be pregnant women because a vaccine could prevent infection, disease, and transmission to their infant before he might be able to be vaccinated.
“There, the primary purpose is to increase the kind of antibody that is transferred across the placenta to the fetus to protect from RSV disease” in the infant after birth, he said. Data suggest it’s possible to increase titer antibodies in infants up to 4 months from maternal immunization, possibly longer, depending on how much the vaccine can induce antibodies in the woman.
For young children, he noted that five live attenuated RSV vaccines are in phase I testing, and four others are in phase I that use a virus vector to deliver the F protein – three using adenovirus and one with a modified vaccinia Ankara virus. A handful of subunit vaccines have reached phase II, and Novavax is furthest along in phase III, but these target older children and adults, including pregnant women.
“There’s going to be a lot of data in the coming year on completed clinical trials, and that’s going to tell us a lot about where we are,” Dr. Anderson said. “The young infant is the most challenging for a vaccine.” But, he added, “new information on protective immunity and disease pathogenesis should help achieve or improve vaccines in the future.”
Dr. Anderson has consulted on RSV vaccines for MedImmune, Novartis, Crucell Holland, and AVC, and has served on a Moderna Therapeutics scientific advisory board. His lab also has received grant funding from Trellis RSV Holdings, and he coinvented several RSV-related vaccine and treatment patents held by the CDC.