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RSV vaccine shows promise in phase 1 trial
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A respiratory syncytial virus vaccine induced a rapid immune response and was associated with acceptable adverse events among healthy young men in a phase 1 trial, according to researchers in Canada.
“In this first-in-humans study the safety, reactogenicity and immunogenicity of a RSV vaccine for pregnant women, containing purified recombinant RSV glycoprotein F engineered to preferentially maintain pre-fusion conformation (RSV-PreF), was evaluated,” Joanne M. Langley, MD, FRCPC, of the Canadian Center for Vaccinology at IWK Health Centre and Nova Scotia Health District Authority, and colleagues wrote.
The researchers randomly assigned 128 healthy men aged 18 to 44 years to 10 μg, 30 μg or 60 μg of RSV-PreF antigen (GlaxoSmithKline Vaccines) with or without an aluminum hydroxide adjuvant, or placebo at three sites in Canada. The median age of participants was 32 years, and 60.9% were white.
Patients assigned to 30 μg RSV-PreF with aluminum hydroxide adjuvant, 60 μg RSV-PreF with adjuvant and 60 μg RSV-PreF without adjuvant experienced the greatest RSV neutralizing antibody responses, according to the researchers.
Thirty days after vaccination, participants who responded to the vaccine had RSV-A neutralizing antibody titer ratios of at least 1:512, and 70% had titers of no less than 1:1,024, with titers increasing 3.2- to 4.9-fold.
Injection site pain (81.3%) and fatigue (43.8%) were the most common adverse events. Severe fatigue occurred among three participants in the vaccine group compared with 33 controls (11.8%-25%). Eight participants in the vaccine group and one control patient reported fever.
In combination with other recent data, this study showed important recent developments in RSV vaccines, Janet A. Englund, MD, a professor of pediatric infectious diseases at the University of Washington and Seattle Children’s Research Institute, and Helen Y. Chu, MD, MPH, assistant professor of allergy and infectious diseases at the University of Washington, wrote in an accompanying editorial.
“This is an exciting time for the RSV field,” they wrote. “Long the neglected back-room orphan virus mentioned only as the cause of annual outbreaks of bronchiolitis in infants, we have new hope that successful collaborations among academicians, clinicians, governmental and international agencies, foundations, regulatory bodies, and the pharmaceutical industry will defeat this important pathogen which impacts both the young and old at all levels of society.” – by Andy Polhamus
Disclosures: This trial was supported by GlaxoSmithKline Biologicals SA. Langley reports receiving research funding from the Canadian Institutes of Health Research, GlaxoSmithKline, Immunovaccine, Novavax, Pan Provincial Vaccine Enterprise (Prevent), Pfizer, the Public Health Agency of Canada and Sanofi Pasteur. Englund reports consulting for Pfizer, being a member of the GlaxoSmithKline DSMB for influenza antivirals and receiving research support for clinical trials from Alios BioPharma, Gilead Sciences, GlaxoSmithKline, Novavax and Pfizer. Please see the full study for a list of all other authors’ relevant financial disclosures.
Perspective
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H. Cody Meissner
RSV lower respiratory tract disease results in hospitalization in about 2% to 3% of the birth cohort in the first 12 months of life in the United States, with the peak hospitalization rate occurring between 30 and 90 days of age. A safe and effective vaccine holds the promise of reducing the burden of RSV disease in children (as well as among the elderly). Because of the adverse experience in the 1960s of enhanced disease among recipients of a formalin-inactivated RSV vaccine, progress in vaccine development has been slow and cautious. But recent advances in understanding the nature of the protective immune response against RSV, as well as advances in the field of vaccinology, have resulted in RSV vaccine development becoming a primary focus for the pharmaceutical industry. At the present time, over 50 novel RSV vaccines are in various stages of development, including a small number of experimental vaccines already in clinical trials, such as the vaccine described by Langley and colleagues.
Four target populations have been identified as likely to benefit from an RSV vaccine based on the epidemiology and burden of RSV disease and include infants in the first months of life (highest priority), children aged at least 6 months, pregnant women and adults over 60 years of age. Approaches to vaccine development fall into three broad categories, including live-attenuated viruses; a vectored vaccine, such as an adenovirus that has been genetically engineered to contain the gene encoding the RSV surface fusion protein; and nonreplicating subunit vaccines.
Because most hospitalizations due to RSV bronchiolitis occur so early in life, vaccine-induced immunity in the infant remains challenging. Immunizing during pregnancy may offer the opportunity to boost maternal anti-RSV neutralizing antibodies that then would be transferred to the infant and offer passive protection for the first few months of life. This approach would be similar to that used for pertussis (Tdap) immunization during pregnancy.
Recent results from a phase 3 trial with an RSV recombinant fusion nanoparticle vaccine among almost 12,000 adults aged 60 years or older failed to meet the pre-specified primary or secondary endpoints. Despite the inability of this particular vaccine trial to demonstrate benefit, hope remains high that other vaccines, such as the one described by Langley and colleagues, will prove to be protective against RSV infection for both mother and infant.
Disclosure: Meissner reports no relevant financial disclosures.
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