Construction of a live-attenuated bivalent vaccine virus against human parainfluenza virus (PIV) types 1 and 2 using
T Tao1, M H Skiadopoulos, F Davoodi
1Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Building 7, Rm 106, 7 Center Drive MSC 0720, Bethesda, MD 20892, USA.
Insights
A new bivalent vaccine candidate, rPIV3-1.2HN, was developed against parainfluenza viruses 1 and 2 (PIV1, PIV2). This live-attenuated vaccine demonstrated efficacy in inducing immunity and resistance to both PIV1 and PIV2 in animal models.
Area of Science:
- Virology
- Vaccinology
- Molecular Biology
Background:
- Parainfluenza viruses 1 and 2 (PIV1, PIV2) are significant causes of pediatric respiratory illness.
- Live-attenuated vaccines are a promising strategy for controlling PIV infections.
- Previous development of a PIV3/PIV1 chimeric virus (rPIV3-1) serves as a foundation for bivalent vaccine construction.
Purpose of the Study:
- To engineer a single live-attenuated virus capable of inducing immunity against both PIV1 and PIV2.
- To evaluate the immunogenicity and protective efficacy of the novel bivalent vaccine candidate.
Main Methods:
- Construction of a recombinant PIV3-based virus (rPIV3-1.2HN) expressing the PIV2 hemagglutinin-neuraminidase (HN) gene.
- Assessment of viral replication, temperature sensitivity, and in vitro growth characteristics.
- Evaluation of vaccine efficacy in a hamster model, including antibody induction and resistance to wild-type PIV challenge.
Main Results:
- The recombinant virus rPIV3-1.2HN was successfully generated and exhibited similar growth properties to its parent virus.
- The PIV2 HN gene insertion conferred an attenuating effect in hamsters, restricting viral replication.
- rPIV3-1.2HN successfully elicited antibodies against both PIV1 and PIV2 and provided protection against challenge with wild-type viruses.
Conclusions:
- The rPIV3-1.2HN virus represents a promising live-attenuated bivalent vaccine candidate against PIV1 and PIV2.
- Attenuating the virus solely through the insertion of the PIV2 HN gene is an effective strategy for bivalent vaccine development.
- This approach offers a potential solution for controlling infections caused by these common pediatric respiratory pathogens.
Abstract:
PIV1 and PIV2 are important agents of pediatric respiratory tract disease. We are developing live-attenuated vaccines against these viruses. We earlier constructed a PIV3/PIV1 antigenic chimeric virus, designated rPIV3-1, in which the hemagglutinin-neuraminidase (HN) and fusion (F) proteins of wild type rPIV3 were replaced by their PIV1 counterparts. In the present study, rPIV3-1 was used as a vector to express the HN protein of PIV2 to generate a single virus capable of inducing immunity to both PIV1 and PIV2. The PIV2 HN open reading frame was expressed from an extra gene cassette, under the control of PIV3 cis-acting transcription signals, inserted between the F and HN genes of rPIV3-1. The recombinant derivative, designated rPIV3-1.2HN, was readily recovered and exhibited a level of temperature sensitivity and in vitro growth similar to that of its parental virus. The rPIV3-1.2HN virus was restricted in replication in both the upper and lower respiratory tracts of hamsters compared with rPIV3-1, identifying an attenuating effect of the PIV2 HN insert in hamsters. rPIV3-1.2HN elicited serum antibodies to both PIV1 and PIV2 and induced resistance against challenge with wild type PIV1 or PIV2. Thus, rPIV3-1.2HN, a virus attenuated solely by the insertion of the PIV2 HN gene, functioned as a live attenuated bivalent vaccine candidate against both PIV1 and PIV2.
