Format

Send to

Choose Destination
Vaccine. 2017 Dec 18;35(51):7139-7146. doi: 10.1016/j.vaccine.2017.10.095. Epub 2017 Nov 16.

Vaccination with a human parainfluenza virus type 3 chimeric FHN glycoprotein formulated with a combination adjuvant induces protective immunity.

Author information

1
VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
2
VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada; Veterinary Microbiology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
3
VIDO-Intervac, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada; Microbiology & Immunology, University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada. Electronic address: sylvia.vandenhurk@usask.ca.

Abstract

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.

KEYWORDS:

Cotton rat; F protein; HN protein; Hamster; Parainfluenzavirus-3

PMID:
29153777
DOI:
10.1016/j.vaccine.2017.10.095
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center