[PMC free article] [PubMed] [CrossRef] [Google Scholar] 31

[PMC free article] [PubMed] [CrossRef] [Google Scholar] 31. F protein, the major RSV neutralization antigen, as an experimental RSV vaccine. The rMPV-RSV-F vectors expressing RSV F from the first, third, or fourth gene position were genetically stable and were not restricted for replication and the family (5) and possesses 10 genes that encode 11 proteins. The fusion (F) and the attachment (G) surface glycoproteins are the two viral neutralization antigens and are the major protective antigens, with F playing the predominant role. RSV F is usually a type I transmembrane envelope glycoprotein that mediates fusion of the virion envelope with the host cell membrane during entry. RSV F-specific neutralizing antibody titers correlate with protection against RSV contamination (6). The clinical use of palivizumab, an F-specific monoclonal antibody, substantially reduces hospitalization for RSV disease in high-risk infants (7). Moreover, the RSV F protein has substantial sequence and antigenic conservation between RSV strains and subgroups, in contrast to the substantial divergence of the G protein. Thus, the F protein is considered to be the most important antigen for an RSV vaccine. RSV vaccines based on inactivated computer virus or protein subunits, when administered to RSV-naive infants and children, are associated with enhanced disease (8,C10) upon subsequent natural RSV exposure and therefore are contraindicated for Abiraterone (CB-7598) this populace. In contrast, live-attenuated RSV strains and parainfluenza computer virus (PIV)-vectored vaccines were not associated with disease enhancement in clinical trials in this populace (11,C13) and thus are safe for pediatric use when suitably attenuated. A live RSV vaccine would be given by the intranasal route and thus has the additional advantage of inducing local immunity at the site of RSV contamination as Abiraterone (CB-7598) well as systemic immunity. The phenomenon of enhanced RSV disease has not been observed in RSV-experienced vaccinees, and therefore adults could safely be immunized with either a live or an inactivated vaccine. (MPV), previously called pneumonia computer virus of mice (PVM), is usually a murine homolog of RSV and belongs to the same genus, (5). Abiraterone (CB-7598) MPV has a genome of approximately 15 kb and has essentially the same array of genes encoding the same constellation of proteins as RSV, namely (listed in 3 to 5 5 gene order), nonstructural protein 1 (NS1), nonstructural protein 2 (NS2), nucleoprotein (N), phosphoprotein (P), matrix protein (M), small hydrophobic protein (SH), attachment glycoprotein (G), fusion glycoprotein (F), M2-1 and M2-2 proteins, and polymerase protein (L). Rabbit polyclonal to KBTBD8 The various genes and proteins of MPV share 30 to 62% nucleotide sequence identity and 10 to 60% amino acid sequence identity with RSV (14). Certain characteristics of MPV make it a stylish vector for developing an RSV vaccine: (i) MPV replicates in the superficial epithelial cells of the respiratory tract, similar to RSV, and thus is expected to induce both systemic immunity and local immune responses in the respiratory tract, where RSV infects and replicates; (ii) MPV was shown to have highly attenuated replication in the respiratory tract of African green monkeys (AGMs) and rhesus macaques, presumably due to host range restriction (15), and therefore would be expected to be highly attenuated in the human respiratory tract; (iii) MPV was surprisingly immunogenic in primates despite the high level of restriction, which was the feature that prompted the present study; (iv) we previously reported that humans do not appear to be naturally exposed to Abiraterone (CB-7598) MPV; and (v) we also reported a lack of significant antigenic reactivity between human or nonhuman primate RSV-specific serum antibodies and MPV, and a lack of cross-protection in mice between RSV and MPV (15). This lack of cross-reaction and cross-neutralization between RSV and MPV would encourage evaluation of an MPV-vectored RSV.