Human respiratory syncytial virus (RSV) is highly infectious and is responsible for considerable mortality and morbidity. In the United States, RSV is responsible for 75,000-125,000 hospitalizations yearly, and worldwide estimates conclude that RSV is responsible for 64 million pediatric infections and 160,000 pediatric deaths. Severe RSV infection in infancy can be followed by years of airway dysfunction, including a predisposition to airway reactivity. RSV infection exacerbates asthma and may be one of its causes. Currently, there is no licensed RSV vaccine and prior RSV vaccine candidates have been linked to increased lung inflammation in vaccinated subjects infected with RSV (Disease Enhancement).
FDA researchers have identified G and F proteins and peptides that elicit an RSV-neutralizing immune response. Lead candidates demonstrated protection against RSV infection in an animal model without Disease Enhancement. The FDA researchers used antigenic mapping to identify peptides that represent epitopes on RSV F and G proteins that are immunogenic and tested the ability of these peptides to induce a neutralizing immune response. FDA researchers have also designed antigenic proteins based on the RSV G protein that form tetrameric G protein and minimize the immune response to vaccination and reduces disease enhancement when vaccinated subjects are infected with RSV. Candidate proteins and peptides were demonstrated to elicit a neutralizing antibody response with sera from vaccinated rabbits and the most promising candidates were tested in challenge studies using mice and cotton rats.
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“Nonglycosylated G-protein Vaccine Protects against Homologous and Heterologous Respiratory Syncytial Virus (RSV) Challenge, while Glycosylated G Enhances RSV Lung Pathology and Cytokine Levels.” J Virol. 2015 Aug;89(16):8193-205. PMID: 26018164 FDA Reference No: E-2013-016
“Antigenic Fingerprinting following Primary RSV infection in Young Children Identifies Novel Antigenic Sites and Reveals Unlinked Evolution of Human Antibody Repertoires to Fusion and Attachment Glycoproteins.” PLoS Pathog 2016 Apr 21; 12(4). PMID: 27100289 FDA Reference No: E-2015-010
“Protective antigenic sites in respiratory syncytial virus G attachment protein outside the central conserved and cysteine noose domains.” PLoS Pathog. 2018 Aug 24; 14(8). PMID: 30142227 FDA Reference No: E-2018-001
E-2013-016, G protein ectodomain: Patent applications filed in the United States (15/100,914), Europe (14821000.8), and India (201647022404)
E-2015-010, Immunogenic F and G Peptides That Elicit Anti-RSV Neutralizing Antibodies. United States patent application: 15/562,862, filed 09.28.2017
E-2018-001, Respiratory Syncytial Virus (RSV) Glycoproteins (G) and fragments without a CCD domain as a vaccine or vaccine component. (PCT/US2018/062623)
Product Area: Respiratory Syncytial Virus (RSV), Vaccines
FDA Reference Nos: E-2013-016, E-2015-010, E-2018-001
Bill Ronnenberg, MS, JD/MIP
FDA Technology Transfer Program