Immunogenicity and Safety of Respiratory Syncytial Virus Subunit Vaccine in Seropositive Children 18-36 Months Old

Abstract

Twenty-six children (aged 18-36 months) previously hospitalized for respiratory syncytial virus (RSV) infection were randomized to receive 50 micrograms of an RSV subunit vaccine composed primarily of F glycoprotein or saline placebo by intramuscular injection. Serum was obtained at entry and at 1 and 6 months after vaccination for detection of antibody to F glycoprotein and G glycoprotein of subtypes A (Ga) or B (Gb) and of neutralizing antibody (nAb). At 1 month, by comparing the baseline values, vaccinees had statistically significant increases in geometric mean antibody titer (GMT) of more than fourfold to F (P = .0001), Ga (P = .0001), Gb (P = .003), and nAb (P = .009). No differences in GMT were observed between F protein vaccine and placebo recipients at entry, nor between placebo recipients at entry and 1 month. RSV infections were identified in 7 placebo recipients (4 by both viral identification and seroconversion, 3 by seroconversion alone). No vaccine recipient had RSV infection documented in the 6 months after vaccination (P = .003). There were no significant vaccine-related side effects, and no evidence of enhanced respiratory illnesses was observed. The subunit F protein vaccine appears safe and immunogenic and may prevent infection in healthy children primed by prior RSV infection.

Animal Pneumoviruses: Molecular Genetics and Pathogenesis

“…Several strategies have been implemented recently in an attempt to generate safe and effective subunit, inactivated, and live-attenuated hRSV vaccines (60, 109). Currently, two promising candidate vaccines under study in clinical trials are an hRSV F subunit vaccine for immunization of patients who have already experienced primary RSV infection, such as the elderly and older hRSV-seropositive children with conditions predisposing them to severe hRSV disease (108, 279,288,354), and cold-passaged, temperature sensitive (cpts) attenuated hRSV strains (196,206). cpts mutant virus strains are difficult, if not impossible, to "fine tune" by serial passage in tissue culture, emphasizing the importance of using newer recombinant (reverse genetics) technologies to advance the field.…”

Replication-Competent or Attenuated, Nonpropagating Vesicular Stomatitis Viruses Expressing Respiratory Syncytial Virus (RSV) Antigens Protect Mice against RSV Challenge

“…A live attenuated RSV vaccine candidate recently reported induced nasal congestion, fussiness, and anorexia in young infants, negating its potential as a vaccine in this age group (57). The immunogenicity of subunit vaccines has been demonstrated in specific human populations; however, the efficacy of this approach has not yet been demonstrated in seronegative infants (5,13,18,37,39,51).…”

“…Although passive immunization is not a practical means of protecting large populations against RSV disease, these findings suggest that vaccines based on the RSV G and/or F glycoprotein may elicit protective immunity. Subunit vaccines based on purified RSV F glycoprotein elicit RSV-specific antibodies in seropositive individuals (5,13,18,37,39,51).…”

Current progress on development of respiratory syncytial virus vaccine

“…Although purified F and G proteins from RSV-infected cultures and F/G chimeric proteins produced by a baculovirus expression system generate antibody responses similar to those observed upon FI-RSV vaccination in rodent models (39,40), the appropriate use of adjuvants could improve immunogenicity and diminish the adverse effects of subunit vaccines (41,42). The purified F protein series (PFP-1, 2 and 3) has been tested in several clinical trials, showing promising results with no obvious adverse events and more than a 4-fold increase in neutralizing antibody titer in the majority of subjects (43)(44)(45). However, the preventive efficacy of PFP vaccination was not significantly different between the vaccine and control groups.…”