The recombinant chimeric human parainfluenza virus type 1 vaccine candidate, rHPIV3–1cp45, is attenuated, immunogenic, and protective in African green monkeys

Vaccine ◽  
2002 ◽  
Vol 20 (13-14) ◽  
pp. 1846-1852 ◽  
Author(s):  
Mario H Skiadopoulos ◽  
Joanne M Tatem ◽  
Sonja R Surman ◽  
Yvonne Mitcho ◽  
Shin-Lu Wu ◽  
...  
Keyword(s):  
Virus Type ◽  
Vaccine Candidate ◽  
Parainfluenza Virus ◽  
Human Parainfluenza Virus ◽  
Green Monkeys

scholarly journals Attenuated Human Parainfluenza Virus Type 1 Expressing Ebola Virus Glycoprotein GP Administered Intranasally Is Immunogenic in African Green Monkeys

2017 ◽  
Vol 91 (10) ◽  
Author(s):  
Matthias Lingemann ◽  
Xueqiao Liu ◽  
Sonja Surman ◽  
Bo Liang ◽  
Richard Herbert ◽  
...  
Keyword(s):  
Virus Type ◽  
Ebola Virus ◽  
Vaccine Candidate ◽  
Serum Antibody ◽  
Parainfluenza Virus ◽  
N Gene ◽  
Vector Particle ◽  
Human Parainfluenza Virus ◽  
Green Monkeys

ABSTRACT The recent 2014-2016 Ebola virus (EBOV) outbreak prompted increased efforts to develop vaccines against EBOV disease. We describe the development and preclinical evaluation of an attenuated recombinant human parainfluenza virus type 1 (rHPIV1) expressing the membrane-anchored form of EBOV glycoprotein GP, as an intranasal (i.n.) EBOV vaccine. GP was codon optimized and expressed either as a full-length protein or as an engineered chimeric form in which its transmembrane and cytoplasmic tail (TMCT) domains were replaced with those of the HPIV1 F protein in an effort to enhance packaging into the vector particle and immunogenicity. GP was inserted either preceding the N gene (pre-N) or between the N and P genes (N-P) of rHPIV1 bearing a stabilized attenuating mutation in the P/C gene (CΔ170). The constructs grew to high titers and efficiently and stably expressed GP. Viruses were attenuated, replicating at low titers over several days, in the respiratory tract of African green monkeys (AGMs). Two doses of candidates expressing GP from the pre-N position elicited higher GP neutralizing serum antibody titers than the N-P viruses, and unmodified GP induced higher levels than its TMCT counterpart. Unmodified EBOV GP was packaged into the HPIV1 particle, and the TMCT modification did not increase packaging or immunogenicity but rather reduced the stability of GP expression during in vivo replication. In conclusion, we identified an attenuated and immunogenic i.n. vaccine candidate expressing GP from the pre-N position. It is expected to be well tolerated in humans and is available for clinical evaluation. IMPORTANCE EBOV hemorrhagic fever is one of the most lethal viral infections and lacks a licensed vaccine. Contact of fluids from infected individuals, including droplets or aerosols, with mucosal surfaces is an important route of EBOV spread during a natural outbreak, and aerosols also might be exploited for intentional virus spread. Therefore, vaccines that protect against mucosal as well as systemic inoculation are needed. We evaluated a version of human parainfluenza virus type 1 (HPIV1) bearing a stabilized attenuating mutation in the P/C gene (CΔ170) as an intranasal vaccine vector to express the EBOV glycoprotein GP. We evaluated expression from two different genome positions (pre-N and N-P) and investigated the use of vector packaging signals. African green monkeys immunized with two doses of the vector expressing GP from the pre-N position developed high titers of GP neutralizing serum antibodies. The attenuated vaccine candidate is expected to be safe and immunogenic and is available for clinical development.

scholarly journals Human parainfluenza virus type 1 regulates cholesterol biosynthesis and establishes quiescent infection in human airway cells

2021 ◽  
Vol 17 (9) ◽  
pp. e1009908
Author(s):  
Yuki Kurebayashi ◽  
Shringkhala Bajimaya ◽  
Masahiro Watanabe ◽  
Nicholas Lim ◽  
Michael Lutz ◽  
...  
Keyword(s):  
Virus Type ◽  
Cholesterol Biosynthesis ◽  
Parainfluenza Virus ◽  
Type I ◽  
Human Airway ◽  
Virion Release ◽  
Infected Cells ◽  
Human Parainfluenza Virus ◽  
Airway Cells

Human parainfluenza virus type 1 (hPIV1) and 3 (hPIV3) cause seasonal epidemics, but little is known about their interaction with human airway cells. In this study, we determined cytopathology, replication, and progeny virion release from human airway cells during long-term infection in vitro. Both viruses readily established persistent infection without causing significant cytopathic effects. However, assembly and release of hPIV1 rapidly declined in sharp contrast to hPIV3 due to impaired viral ribonucleocapsid (vRNP) trafficking and virus assembly. Transcriptomic analysis revealed that both viruses induced similar levels of type I and III IFNs. However, hPIV1 induced specific ISGs stronger than hPIV3, such as MX2, which bound to hPIV1 vRNPs in infected cells. In addition, hPIV1 but not hPIV3 suppressed genes involved in lipid biogenesis and hPIV1 infection resulted in ubiquitination and degradation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, a rate limiting enzyme in cholesterol biosynthesis. Consequently, formation of cholesterol-rich lipid rafts was impaired in hPIV1 infected cells. These results indicate that hPIV1 is capable of regulating cholesterol biogenesis, which likely together with ISGs contributes to establishment of a quiescent infection.

scholarly journals A study of genetic variability of human parainfluenza virus type 1 in Croatia, 2011–2014

2016 ◽  
Vol 65 (8) ◽  
pp. 793-803 ◽  
Author(s):  
Tanja Košutić-Gulija ◽  
Anamarija Slovic ◽  
Sunčanica Ljubin-Sternak ◽  
Gordana Mlinarić-Galinović ◽  
Dubravko Forčić
Keyword(s):  
Genetic Variability ◽  
Virus Type ◽  
Parainfluenza Virus ◽  
Human Parainfluenza Virus

scholarly journals A novel human parainfluenza virus type 1 (HPIV1) with separated P and C genes is useful for generating C gene mutants for evaluation as live-attenuated virus vaccine candidates

Vaccine ◽  
2010 ◽  
Vol 28 (3) ◽  
pp. 767-779 ◽  
Author(s):  
Emmalene J. Bartlett ◽  
Ann-Marie Cruz ◽  
Jim Boonyaratanakornkit ◽  
Janice Esker ◽  
Adam Castaño ◽  
...  
Keyword(s):  
Virus Type ◽  
Virus Vaccine ◽  
Parainfluenza Virus ◽  
Vaccine Candidates ◽  
Attenuated Virus ◽  
Human Parainfluenza Virus

scholarly journals Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1) vaccine candidates containing stabilized mutations in the P/C and L genes

2007 ◽  
Vol 4 (1) ◽  
pp. 67 ◽  
Author(s):  
Emmalene J Bartlett ◽  
Adam Castaño ◽  
Sonja R Surman ◽  
Peter L Collins ◽  
Mario H Skiadopoulos ◽  
...  
Keyword(s):  
Virus Type ◽  
Parainfluenza Virus ◽  
Vaccine Candidates ◽  
Human Parainfluenza Virus

Viral Cross-Reactivity and Antigenic Determinants Recognized by Human Parainfluenza Virus Type 1-Specific Cytotoxic T-Cells

Virology ◽  
1994 ◽  
Vol 199 (2) ◽  
pp. 376-383 ◽  
Author(s):  
Vibhuti P. Dave ◽  
Jane E. Allan ◽  
Karen S. Slobod ◽  
F.Suzette Smith ◽  
Kevin W. Ryan ◽  
...  
Keyword(s):  
T Cells ◽  
Virus Type ◽  
Cytotoxic T Cells ◽  
Cross Reactivity ◽  
Parainfluenza Virus ◽  
Antigenic Determinants ◽  
Human Parainfluenza Virus

scholarly journals Generation of Recombinant Human Parainfluenza Virus Type 1 Vaccine Candidates by Importation of Temperature-Sensitive and Attenuating Mutations from Heterologous Paramyxoviruses

2004 ◽  
Vol 78 (4) ◽  
pp. 2017-2028 ◽  
Author(s):  
Jason T. Newman ◽  
Jeffrey M. Riggs ◽  
Sonja R. Surman ◽  
Josephine M. McAuliffe ◽  
Teresa A. Mulaikal ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Virus Type ◽  
Neutralizing Antibodies ◽  
Effective Means ◽  
Parainfluenza Virus ◽  
Temperature Sensitive ◽  
C Protein ◽  
Vaccine Candidates ◽  
Human Parainfluenza Virus

ABSTRACT Human parainfluenza virus type 1 (HPIV1) is a significant cause of respiratory tract disease in infants and young children for which a vaccine is needed. In the present study, we sought to attenuate HPIV1 by the importation of one or more known attenuating point mutations from heterologous paramyxoviruses into homologous sites in HPIV1. The introduced mutations were derived from three attenuated paramyxoviruses: (i) HPIV3cp45, a live-attenuated HPIV3 vaccine candidate containing multiple attenuating mutations; (ii) the respiratory syncytial virus cpts530 with an attenuating mutation in the L polymerase protein; and (iii) a murine PIV1 (MPIV1) attenuated by a mutation in the accessory C protein. Recombinant HPIV1 (rHPIV1) mutants bearing a single imported mutation in C, any of three different mutations in L, or a pair of mutations in F exhibited a 100-fold or greater reduction in replication in the upper or lower respiratory tract of hamsters. Both temperature-sensitive (ts) (mutations in the L and F proteins) and non-ts (the mutation in the C protein) attenuating mutations were identified. rHPIV1 mutants containing a combination of mutations in L were generated that were more attenuated than viruses bearing the individual mutations, showing that the systematic accretion of mutations can yield progressive increases in attenuation. Hamsters immunized with rHPIV1 mutants bearing one or two mutations developed neutralizing antibodies and were resistant to challenge with wild-type HPIV1. Thus, importation of attenuating mutations from heterologous viruses is an effective means for rapidly identifying mutations that attenuate HPIV1 and for generating live-attenuated HPIV1 vaccine candidates.

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