Human parainfluenza virus type 3 (PIV3) is a major cause of lower respiratory disease i.e. bronchitis， bronchiolitis or pneumonia， in infants and young children. Presently there is no licensed vaccine against PIV3. To produce an effective subunit vaccine， a chimeric FHN glycoprotein consisting of the N-terminal ectodomain of the fusion (F) protein linked to the haemagglutinin-neuraminidase (HN) protein without transmembrane domain， and secreted forms of the individual F and HN glycoproteins， were expressed in mammalian cells and purified. Mice and cotton rats were immunized intramuscularly (IM) with FHN or both F and HN proteins (F?+?HN)， formulated with poly(I:C) and an innate defense regulator... More
Human parainfluenza virus type 3 (PIV3) is a major cause of lower respiratory disease i.e. bronchitis， bronchiolitis or pneumonia， in infants and young children. Presently there is no licensed vaccine against PIV3. To produce an effective subunit vaccine， a chimeric FHN glycoprotein consisting of the N-terminal ectodomain of the fusion (F) protein linked to the haemagglutinin-neuraminidase (HN) protein without transmembrane domain， and secreted forms of the individual F and HN glycoproteins， were expressed in mammalian cells and purified. Mice and cotton rats were immunized intramuscularly (IM) with FHN or both F and HN proteins (F?+?HN)， formulated with poly(I:C) and an innate defense regulator peptide in polyphosphazene (TriAdj). Significantly higher levels of systemic virus-neutralizing antibodies were observed in mice and cotton rats immunized with FHN/TriAdj when compared to animals immunized with the combination of F and HN proteins (F?+?HN/TriAdj). As PIV3 is a pneumotropic virus， another goal is to produce an effective mucosal subunit vaccine. Intranasal (IN) administration with FHN/TriAdj resulted in mucosal IgA production in the lung and virus neutralizing antibodies in the sera. After PIV3 challenge no virus was detected in cotton rats immunized with FHN/TriAdj regardless of the route of delivery. Protective immunity against PIV3 was also induced by FHN/TriAdj in hamsters. In conclusion， the FHN protein formulated with TriAdj has potential for development of a safe and effective vaccine against PIV3.
