Influence of Antigen Insertion Site and Vector Dose on Immunogenicity and Protective Capacity in Sendai Virus-based Human Parainfluenza Virus Type 3 Vaccines

Overview

Journal J Virol

Publisher American Society for Microbiology

Date 2013 Mar 22

PMID 23514887

Citations 5

Authors

John N Mason

Husni Elbahesh

Charles J Russell

Affiliations

Soon will be listed here.

Abstract

Recombinant Sendai virus (rSeV) was used as a live, attenuated vaccine vector for intranasal inoculation and mucosal expression of the hemagglutinin-neuraminidase (HN) surface glycoprotein of human parainfluenza virus type 3 (HPIV3). Two vaccine candidates rSeV-HPIV3HN(P-M) and rSeV-HPIV3(F-HN) were constructed in which the HPIV3 HN open reading frame and an additional gene junction was inserted in the P-M and F-HN gene junctions of rSeV, respectively. The rSeV-HPIV3HN(P-M) virus was attenuated compared to rSeV-HPIV3(F-HN) in LLC-MK2 cells, and yet both vaccine candidates grew to similar extents in NHBE cells and in the respiratory tracts of cotton rats. These results suggest that in vitro vector growth in NHBE cells more accurately predicts virus yield in cotton rats than does growth in LLC-MK2 cells. Both vaccine vectors elicited high levels of serum neutralizing antibodies and conferred protection from HPIV3 challenge in cotton rats. Compared to vaccination with a high dose (2,000,000 PFU), intranasal inoculation with a low dose (200 PFU) resulted in a 10-fold decrease in vector growth in the nasal cavity and trachea and a 50-fold decrease in the lungs. However, low-dose vaccination resulted in only modest decreases in anti-HPIV3 antibodies in sera and was sufficient to confer complete protection from HPIV3 challenge. Varying the HPIV3 antigen insertion site and vector dose allowed fine-tuning of the in vivo growth and immunogenicity of rSeV-based vaccines, but all four vaccination strategies tested resulted in complete protection from HPIV3 challenge. These results highlight the versatility of the rSeV platform for developing intranasally administered respiratory virus vaccines.

Citing Articles

Sendai Virus-Vectored Vaccines That Express Envelope Glycoproteins of Respiratory Viruses.

Russell C, Hurwitz J Viruses. 2021; 13(6).

PMID: 34072332 PMC: 8230104. DOI: 10.3390/v13061023.

A CD8 T-cell epitope variant enhances immune targeting to a recombinant picornavirus vaccine antigen.

Bell M, Renner D, Johnson A, Pavelko K Viral Immunol. 2014; 27(7):361-6.

PMID: 25025983 PMC: 4150375. DOI: 10.1089/vim.2014.0045.

Novel roles of focal adhesion kinase in cytoplasmic entry and replication of influenza A viruses.

Elbahesh H, Cline T, Baranovich T, Govorkova E, Schultz-Cherry S, Russell C J Virol. 2014; 88(12):6714-28.

PMID: 24696469 PMC: 4054363. DOI: 10.1128/JVI.00530-14.

Chimeric bovine/human parainfluenza virus type 3 expressing respiratory syncytial virus (RSV) F glycoprotein: effect of insert position on expression, replication, immunogenicity, stability, and protection against RSV infection.

Liang B, Munir S, Amaro-Carambot E, Surman S, Mackow N, Yang L J Virol. 2014; 88(8):4237-50.

PMID: 24478424 PMC: 3993740. DOI: 10.1128/JVI.03481-13.

Development of oligomannose-coated liposome-based nasal vaccine against human parainfluenza virus type 3.

Senchi K, Matsunaga S, Hasegawa H, Kimura H, Ryo A Front Microbiol. 2013; 4:346.

PMID: 24324462 PMC: 3840497. DOI: 10.3389/fmicb.2013.00346.

References

Tompkins S, Lin Y, Leser G, Kramer K, Haas D, Howerth E . Recombinant parainfluenza virus 5 (PIV5) expressing the influenza A virus hemagglutinin provides immunity in mice to influenza A virus challenge. Virology. 2007; 362(1):139-50. PMC: 1995462. DOI: 10.1016/j.virol.2006.12.005. View

Girard M, Cherian T, Pervikov Y, Kieny M . A review of vaccine research and development: human acute respiratory infections. Vaccine. 2005; 23(50):5708-24. PMC: 7130922. DOI: 10.1016/j.vaccine.2005.07.046. View

Fuerst T, Niles E, Studier F, Moss B . Eukaryotic transient-expression system based on recombinant vaccinia virus that synthesizes bacteriophage T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986; 83(21):8122-6. PMC: 386879. DOI: 10.1073/pnas.83.21.8122. View

Gomez M, Mufson M, Dubovsky F, Knightly C, Zeng W, Losonsky G . Phase-I study MEDI-534, of a live, attenuated intranasal vaccine against respiratory syncytial virus and parainfluenza-3 virus in seropositive children. Pediatr Infect Dis J. 2009; 28(7):655-8. DOI: 10.1097/INF.0b013e318199c3b1. View

Feldmann H, Volchkov V, Volchkova V, Stroher U, Klenk H . Biosynthesis and role of filoviral glycoproteins. J Gen Virol. 2001; 82(Pt 12):2839-2848. DOI: 10.1099/0022-1317-82-12-2839. View

Ball L, White C . Order of transcription of genes of vesicular stomatitis virus. Proc Natl Acad Sci U S A. 1976; 73(2):442-6. PMC: 335925. DOI: 10.1073/pnas.73.2.442. View

Schmidt A, Wenzke D, McAuliffe J, St Claire M, Elkins W, Murphy B . Mucosal immunization of rhesus monkeys against respiratory syncytial virus subgroups A and B and human parainfluenza virus type 3 by using a live cDNA-derived vaccine based on a host range-attenuated bovine parainfluenza virus type 3 vector backbone. J Virol. 2002; 76(3):1089-99. PMC: 135799. DOI: 10.1128/jvi.76.3.1089-1099.2002. View

Abraham G, Banerjee A . Sequential transcription of the genes of vesicular stomatitis virus. Proc Natl Acad Sci U S A. 1976; 73(5):1504-8. PMC: 430325. DOI: 10.1073/pnas.73.5.1504. View

Agungpriyono D, Yamaguchi R, Uchida K, Tohya Y, Kato A, Nagai Y . Green fluorescent protein gene insertion of Sendai Virus infection in nude mice: possibility as an infection tracer. J Vet Med Sci. 2000; 62(2):223-8. DOI: 10.1292/jvms.62.223. View

10.

Griffin M, Walker F, Iwane M, Weinberg G, Staat M, Erdman D . Epidemiology of respiratory infections in young children: insights from the new vaccine surveillance network. Pediatr Infect Dis J. 2004; 23(11 Suppl):S188-92. DOI: 10.1097/01.inf.0000144660.53024.64. View

11.

Collins P, Hightower L, Ball L . Transcriptional map for Newcastle disease virus. J Virol. 1980; 35(3):682-93. PMC: 288862. DOI: 10.1128/JVI.35.3.682-693.1980. View

12.

Piazza F, Johnson S, Darnell M, PORTER D, Hemming V, Prince G . Bovine respiratory syncytial virus protects cotton rats against human respiratory syncytial virus infection. J Virol. 1993; 67(3):1503-10. PMC: 237520. DOI: 10.1128/JVI.67.3.1503-1510.1993. View

13.

Zhan X, Slobod K, Krishnamurthy S, Luque L, Takimoto T, Jones B . Sendai virus recombinant vaccine expressing hPIV-3 HN or F elicits protective immunity and combines with a second recombinant to prevent hPIV-1, hPIV-3 and RSV infections. Vaccine. 2008; 26(27-28):3480-8. PMC: 2728217. DOI: 10.1016/j.vaccine.2008.04.022. View

14.

Hu H, Roth J, Estevez C, Zsak L, Liu B, Yu Q . Generation and evaluation of a recombinant Newcastle disease virus expressing the glycoprotein (G) of avian metapneumovirus subgroup C as a bivalent vaccine in turkeys. Vaccine. 2011; 29(47):8624-33. DOI: 10.1016/j.vaccine.2011.09.007. View

15.

He B, Lamb R . Effect of inserting paramyxovirus simian virus 5 gene junctions at the HN/L gene junction: analysis of accumulation of mRNAs transcribed from rescued viable viruses. J Virol. 1999; 73(8):6228-34. PMC: 112699. DOI: 10.1128/JVI.73.8.6228-6234.1999. View

16.

Luque L, Russell C . Spring-loaded heptad repeat residues regulate the expression and activation of paramyxovirus fusion protein. J Virol. 2007; 81(7):3130-41. PMC: 1866055. DOI: 10.1128/JVI.02464-06. View

17.

Pattnaik A, Wertz G . Replication and amplification of defective interfering particle RNAs of vesicular stomatitis virus in cells expressing viral proteins from vectors containing cloned cDNAs. J Virol. 1990; 64(6):2948-57. PMC: 249479. DOI: 10.1128/JVI.64.6.2948-2957.1990. View

18.

Murphy B, Hall S, Kulkarni A, Crowe Jr J, Collins P, Connors M . An update on approaches to the development of respiratory syncytial virus (RSV) and parainfluenza virus type 3 (PIV3) vaccines. Virus Res. 1994; 32(1):13-36. DOI: 10.1016/0168-1702(94)90059-0. View

19.

Bousse T, Chambers R, Scroggs R, Portner A, Takimoto T . Human parainfluenza virus type 1 but not Sendai virus replicates in human respiratory cells despite IFN treatment. Virus Res. 2006; 121(1):23-32. DOI: 10.1016/j.virusres.2006.03.012. View

20.

Horikami S, Curran J, Kolakofsky D, Moyer S . Complexes of Sendai virus NP-P and P-L proteins are required for defective interfering particle genome replication in vitro. J Virol. 1992; 66(8):4901-8. PMC: 241329. DOI: 10.1128/JVI.66.8.4901-4908.1992. View