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A chimeric glycoprotein formulated with a combination adjuvant induces protective immunity against both human respiratory syncytial virus and parainfluenza virus type 3
- Source :
- Antiviral research. 158
- Publication Year :
- 2018
-
Abstract
- Human respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) are major causes of serious lower respiratory tract disease in infants. Currently there is no licensed vaccine against RSV or PIV3. To make an effective bivalent subunit vaccine, a chimeric truncated FRHN protein containing the N-terminal ectodomain of the RSV fusion (F) protein linked to the C-terminal ectodomain of the PIV3 haemagglutinin-neuraminidase (HN) protein was produced in HEK293T cells. Mice, cotton rats and hamsters were immunized intramuscularly (IM) with both RSV F and PIV3 HN (FR+HN) or FRHN, formulated with TriAdj, which consists of poly(I:C), innate defense regulator peptide and poly[di(sodium carboxylatoethylphenoxy)]-phosphazene. Both formulations were immunogenic and elicited full protection from RSV; however, animals vaccinated with FRHN/TriAdj were significantly better protected from PIV3 than animals vaccinated with FR+HN/TriAdj. To develop a potentially more effective subunit vaccine, a chimeric glycoprotein (FRipScHN), encoding the RSV F ectodomain stabilized in the pre-fusion form linked to PIV3 HN was generated. Intramuscular vaccination with FRipScHN/TriAdj induced virus neutralizing antibodies followed by complete protection from RSV and PIV3 replication in the lungs of challenged cotton rats. Furthermore, intranasal vaccination with FRipScHN/TriAdj significantly reduced both RSV and PIV3 replication in cotton rats. Mucosal immunization with FRipScHN/TriAdj also elicited strong antigen-specific mucosal and systemic immune responses in a lamb model. In conclusion, the chimeric FRipScHN protein combined with TriAdj has potential for development of a safe, effective, bivalent vaccine against both RSV and PIV3.
- Subjects :
- 0301 basic medicine
viruses
medicine.medical_treatment
Respiratory Syncytial Virus Infections
Protective Agents
Virus Replication
Respirovirus Infections
Virus
03 medical and health sciences
Mice
Immune system
Adjuvants, Immunologic
Virology
Cricetinae
Chlorocebus aethiops
medicine
Respiratory Syncytial Virus Vaccines
Animals
Humans
Cotton rat
Sigmodontinae
Immunity, Mucosal
Glycoproteins
Pharmacology
Mice, Inbred BALB C
Sheep
biology
Vaccination
Chimerin Proteins
biology.organism_classification
Fusion protein
Immunity, Innate
3. Good health
Parainfluenza Virus 3, Human
Disease Models, Animal
030104 developmental biology
HEK293 Cells
Poly I-C
Ectodomain
Respiratory Syncytial Virus, Human
Vaccines, Subunit
biology.protein
Immunization
Antibody
Adjuvant
Viral Fusion Proteins
Subjects
Details
- ISSN :
- 18729096
- Volume :
- 158
- Database :
- OpenAIRE
- Journal :
- Antiviral research
- Accession number :
- edsair.doi.dedup.....ec1b841ea5a731f3a5aeb833b2579cf6