- Clinical Trials
- Research News
- Industry Trends
- Agency Actions
- Drug Safety Issues
- Approvals, Launches, & New Indications
- Health Care Reform
Positive Phase II Results With Respiratory Virus Vaccine in Women of Childbearing Age
Vaccine candidate may have role in maternal immunization (Apr. 2)
A phase II dose-ranging trial has demonstrated the safety and immunogenicity of a respiratory syncytial virus (RSV) vaccine candidate (Novavax, Inc.) for use in a maternal immunization strategy. In such a strategy, the antibodies in vaccinated women can be expected to be naturally transferred to their infants in utero and thereby may confer passive protection at the earliest stage of life when these infants are vulnerable to severe respiratory disease due to RSV infection.
The randomized, blinded, placebo-controlled phase II study evaluated two dose levels of an RSV F protein nanoparticle vaccine candidate with and without aluminum phosphate (alum) as an adjuvant. The study enrolled 330 women of childbearing age, who received either one or two intramuscular injections of a single dose of vaccine or placebo at study day 0 and day 28. Vaccine doses of 60 and 90 mcg were tested, with or without aluminum phosphate as an adjuvant. Safety and immunogenicity data have been evaluated through day 56.
The study’s primary objectives measured the difference in anti-F immunoglobulin G (IgG) elicited by the use of alum adjuvant (one versus two immunizations) and across doses (60 and 90 mcg). The use of alum enhanced anti-F IgG responses to both the single-dose and two-dose regimens, with the greatest responses observed using a two-dose regimen.
Peak geometric mean titers of anti-F IgG in the two-dose alum groups ranged from 12,000 to 14,000, representing a 13- to 16-fold increase, compared with a six- to 10-fold increase in the non-alum groups. Minimal increases were achieved by increasing the doses from 60 mcg to 90 mcg. Peak geometric mean RSV A neutralizing antibodies in the alum groups ranged from log2 9.5 to log2 10.5, representing a 3.1- to 3.8-fold increase. Palivizumab-like antibody titers increased eight- to nine-fold, with four-fold increases in = 92% of vaccine recipients in the groups given two-dose alum-adjuvanted vaccine.
Globally, RSV is a common cause of childhood respiratory infection, with a disease burden of 64 million cases and approximately 160,000 deaths annually. Severe RSV disease results in 3.4 million hospital admissions per year globally and disproportionately affects infants younger than 6 months of age. RSV infection is the leading cause of hospitalization during the first months of life, an age at which implementation of complete active (direct) immunization is generally considered unlikely to succeed. More than half of RSV-related hospitalizations in the U.S. occur in infants 3 months of age or younger. No approved RSV prophylactic vaccines are currently available.
Maternal immunization is a strategy that can be used to protect infants from a variety of infectious diseases during the first months of life if enough protective antibodies can be transferred from mother to child. Such immunization is recommended by the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices (ACIP) for preventing infant pertussis disease (whooping cough). Vaccine-induced maternal antibodies cross the placenta and often achieve concentrations in the fetus in excess of those seen in maternal sera. These naturally transferred antibodies are known to provide protection to the infant against many infectious diseases based on the exposure history of the mother, including protection against RSV infection during the first weeks of life. As the maternally derived antibody titers decrease over time, infants become more susceptible to RSV disease. Field studies indicate that high concentrations of antibody in mothers due to natural exposure is correlated with lower RSV infection rates in newborns.
Source: Novavax, Inc.; April 2, 2013.