Evaluation of Combined Live, Attenuated Respiratory Syncytial Virus and Parainfluenza 3 Virus Vaccines in Infants and Young Children

Abstract

We evaluated a combination respiratory syncytial virus (RSV) and parainfluenza 3 virus (PIV3) live, attenuated intranasal vaccine for safety, viral replication, and immunogenicity in doubly seronegative children 6-18 months old. RSV cpts-248/404 and PIV3-cp45 vaccines were combined in a dose of 10(5) plaque-forming units of each per 0.5-mL dose and compared with monovalent vaccines or placebo. The virus shedding pattern of RSV was not different between monovalent RSV cpts-248/404 vaccine and combination vaccine. Modest reductions in the shedding of PIV3-cp45 vaccine virus were found after the administration of RSV cpts-248/404 and PIV3-cp45 vaccine, relative to monovalent PIV3 vaccine; 16 (76%) of 21 children given combination vaccine shed PIV3-cp45 versus 11 (92%) of 12 of those given monovalent PIV3 vaccine. Both vaccines were immunogenic, and antibody responses were similar between the monovalent groups and the combination group. Combined RSV/PV3 vaccine is feasible for simultaneous administration, and further studies are warranted.

Evaluation of dual nasal delivery of infectious hematopoietic necrosis virus and enteric red mouth vaccines in rainbow trout (Oncorhynchus mykiss)

“…For instance, the human influenza virus nasal vaccine FluMist is a quadrivalent viral vaccine and trivalent nasal influenza vaccine has been shown to provide immediate protection in children [16]. Combined RSV/PV3 vaccine is feasible for simultaneous nasal administration in children [17]. However, to the best of our knowledge, this is the first report where each nare/nostril is used separately to receive a different vaccine.…”

“…Nasal delivery with more than one vaccine has been tested in a number of mammalian studies [16][17][18][19][20][21][22]. For instance, the human influenza virus nasal vaccine FluMist is a quadrivalent viral vaccine and trivalent nasal influenza vaccine has been shown to provide immediate protection in children [16].…”

Intranasal Drug Delivery: How, Why and What for?

“…The nasal associated lymphoid tissue is composed of agglomerates of dendritic cells, Tcells and B-cells which are involved in the initiation and execution of immune responses (68). Examples of the human efficacy of intranasal vaccines include those against influenza A and B virus, proteosoma-influenza (69), adenovirus-vectored influenza (70), group B meningococcal native (71), attenuated respiratory syncytial virus (72) and parainfluenza 3 virus (72,73) (Table 2). However, human nasal vaccination is not restricted to the upper airways affections.…”

Increased Genetic and Phenotypic Stability of a Promising Live-Attenuated Respiratory Syncytial Virus Vaccine Candidate by Reverse Genetics

“…A long-standing goal has been the development of a pediatric live-attenuated intranasal vaccine that is safe and well tolerated yet satisfactorily immunogenic in the target population, young infants under 6 months of age. Several biologically derived vaccine candidates have been tested in clinical trials, beginning in the 1960s, but were found to be unsatisfactorily attenuated and in some cases exhibited genetic instability (2,19,20,35,37). More recently, reverse genetics has been used both to identify existing and create new attenuating mutations and to make new cDNAderived vaccine candidates containing desired combinations of mutations (7,18,36).…”