PMID- 37503102
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240226
DP  - 2023 Jul 18
TI  - A parainfluenza virus 5 (PIV5)-vectored intranasal vaccine for Lyme disease 
      provides long-lasting protection against tick transmitted Borrelia burgdorferi in 
      mice.
LID - rs.3.rs-3143132 [pii]
LID - 10.21203/rs.3.rs-3143132/v1 [doi]
AB  - Lyme disease (LD) is the most prevalent vector borne disease in North America and 
      Europe and its geographic range continues to expand. Strategies for disease 
      control are necessary to effectively reduce incidence of LD including development 
      of safe vaccines for human use. Parainfluenza virus 5 (PIV5) vector has an 
      excellent safety record in animals and PIV5-vectored COVID-19 and RSV vaccines 
      are currently under clinical development. We constructed PIV5-vectored LD vaccine 
      candidates expressing OspA from B. burgdorferi sensu stricto (OspA(B31)) and a 
      chimeric protein containing sequences from B. burgdorferi and B. afzelii 
      (OspA(BPBPk)). Immunogenicity and vaccine efficacy were analyzed in C3H-HeN mice 
      after prime-boost intranasal (IN) vaccination with PIV5-OspA(B31) and 
      PIV5-OspA(BPBPk), subcutaneous (SC) vaccination with rOspA(B31)+Alum as well as 
      the respective controls. Mice vaccinated with either PIV5-A(B31) or PIV5-A(BPBPk) 
      intranasally had high endpoint titers of serum antibody against OspA antigen 
      beyond 1 year post vaccination, similar to levels detected in mice vaccinated SC 
      with rOspA(B31). Flowcytometric analysis of spleen cells at 9-months 
      post-immunization demonstrated that immunization with the intranasal PIV5 vaccine 
      candidates led to an overall increase in the number of memory B cells, cytotoxic 
      T and cytotoxic effector T cells compared to SC groups. Borreliacidal activity 
      measured by neutralization assay was maintained up to 18 months 
      post-immunization, with the response greater in intranasal PIV5-delivered OspA 
      vaccines, than that induced by SC rOspA(B31). Challenge with infected ticks 
      (10-19 strains of B. burgdorferi) performed at 4-, 9- or 15-months 
      post-immunization showed increased breakthrough infections in mice vaccinated 
      with SC rOspA(B31) compared to IN PIV5-A(B31) or IN PIV5-A(BPBPk) at 9- and 
      15-months, as determined by qPCR of B. burgdorferi in tissues, culture of B. 
      burgdorferi from tissues, and antibodies against B. burgdorferi protein VIsE. 
      These data demonstrate that intranasal PIV5-based immunization is superior to 
      parenteral immunization with the same recombinant protein and provides 
      long-lasting protection (> 1 year) against Lyme disease.
FAU - Gingerich, Maria Cristina
AU  - Gingerich MC
AD  - Department of Infectious Diseases, College of Veterinary Medicine, University of 
      Georgia, Athens, GA, USA.
AD  - CyanVac, LLC, Athens, GA, USA.
FAU - Nair, Nisha
AU  - Nair N
AD  - Department of Microbiology, Immunology, and Biochemistry, University of Tennessee 
      Health Science Center, Tennessee, USA.
FAU - Azevedo, J Filipe
AU  - Azevedo JF
AD  - Department of Microbiology, Immunology, and Biochemistry, University of Tennessee 
      Health Science Center, Tennessee, USA.
AD  - Immuno Technologies, Inc., Memphis, TN, USA.
FAU - Samanta, Kamalika
AU  - Samanta K
AUID- ORCID: 0000-0001-6456-601X
AD  - Department of Microbiology, Immunology, and Biochemistry, University of Tennessee 
      Health Science Center, Tennessee, USA.
FAU - Kundu, Suman
AU  - Kundu S
AD  - Department of Microbiology, Immunology, and Biochemistry, University of Tennessee 
      Health Science Center, Tennessee, USA.
AD  - Immuno Technologies, Inc., Memphis, TN, USA.
FAU - He, Biao
AU  - He B
AD  - Department of Infectious Diseases, College of Veterinary Medicine, University of 
      Georgia, Athens, GA, USA.
AD  - CyanVac, LLC, Athens, GA, USA.
FAU - Gomes-Solecki, Maria
AU  - Gomes-Solecki M
AUID- ORCID: 0000-0002-3715-4543
AD  - Department of Microbiology, Immunology, and Biochemistry, University of Tennessee 
      Health Science Center, Tennessee, USA.
AD  - Immuno Technologies, Inc., Memphis, TN, USA.
LA  - eng
GR  - R01 AI139267/AI/NIAID NIH HHS/United States
GR  - R43 AI155211/AI/NIAID NIH HHS/United States
GR  - R44 AI167605/AI/NIAID NIH HHS/United States
PT  - Preprint
DEP - 20230718
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
UIN - NPJ Vaccines. 2024 Feb 15;9(1):33. PMID: 38360853
PMC - PMC10371166
COIS- Ethics Declarations / Competing Interests MGS is the President and CEO of Immuno 
      Technologies, Inc. BH is President and CEO of CyanVac, LLC and holds patents that 
      covers use of PIV5 vaccine delivery vectors. The other authors have no competing 
      interests.
EDAT- 2023/07/28 06:42
MHDA- 2023/07/28 06:43
PMCR- 2023/07/26
CRDT- 2023/07/28 04:26
PHST- 2023/07/28 06:42 [pubmed]
PHST- 2023/07/28 06:43 [medline]
PHST- 2023/07/28 04:26 [entrez]
PHST- 2023/07/26 00:00 [pmc-release]
AID - rs.3.rs-3143132 [pii]
AID - 10.21203/rs.3.rs-3143132/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Jul 18:rs.3.rs-3143132. doi: 10.21203/rs.3.rs-3143132/v1.