Methods: This phase I, double blind, placebo controlled study randomized (2:1) RSV-seronegative children 6 to 24 months of age to receive a single intranasal dose of vaccine (RSVcps2) or placebo. Children were monitored with frequent contacts (including nasal wash (NW) samples on >11 occasions through day 28) during the first 56 days and weekly during the RSV season (November-March). Infectivity was determined by quantitative culture (plaque forming units (PFU)/mL) and rRT qPCR (copies/mL) in NW fluid. NW fluid was tested for respiratory viral pathogens by Fast Track PCR when respiratory symptoms were reported.
Results: Fifty-one children were enrolled from five sites in October, 2013 (17 children) and between April and October, 2014 (34 children); enrollment was suspended during the intervening RSV season. Fifty children received study product and completed the study. The average age was 12 months (range 6-23 months); 58% were male, 28% were Black and 47% were HIV-exposed but uninfected. Vaccine and placebo recipients commonly experienced mild and moderate adverse events, primarily respiratory illnesses that occurred in 44% of both groups. No Grade 4 or serious adverse events occurred. Twenty-six of 34 (77%) vaccine recipients had vaccine shedding detected by viral culture (15 vaccinees) or qPCR (26 vaccinees). Among those who tested positive, the mean peak titer by culture was 1.7 log10 PFU/ml (SD=1.0) and the mean peak titer by qPCR was 3.3 log10 copies/mL (SD=0.9). No placebo recipients had vaccine virus detected. There was no evidence of RSV disease enhancement when RSV infection occurred during RSV season. Determination of neutralizing antibody responses and RSV F IgG antibody responses is in progress.
Conclusion: The RSVcps2 vaccine has excellent infectivity and is well tolerated in sero-negative infants and children. Further evaluation of this candidate vaccine is warranted.
C. K. Cunningham,
P. Muresan, None
E. Mcfarland, None
C. Luongo, None
P. Collins, MedImmune: Collaborative Research Agreement (CRADA) , Research support
B. Thumar, None
E. Schappell, None
D. Gnanashanmugam, None
G. Siberry, None
V. Rexroad, None
R. Karron, NIH: Research Contractor , Research support