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Replication-incompetent rabies virus vector harboring glycoprotein gene of lymphocytic choriomeningitis virus (LCMV) protects mice from LCMV challenge.
PLoS Negl Trop Dis. 2018 04; 12(4):e0006398.PN

Abstract

BACKGROUND

Lymphocytic choriomeningitis virus (LCMV) causes a variety of diseases, including asymptomatic infections, meningitis, and congenital infections in the fetus of infected mother. The development of a safe and effective vaccine against LCMV is imperative. This study aims to develop a new candidate vaccine against LCMV using a recombinant replication-incompetent rabies virus (RV) vector.

METHODOLOGY/PRINCIPAL FINDINGS

In this study, we have generated a recombinant deficient RV expressing the LCMV glycoprotein precursor (GPC) (RVΔP-LCMV/GPC) which is lacking the RV-P gene. RVΔP-LCMV/GPC is able to propagate only in cells expressing the RV-P protein. In contrast, the LCMV-GPC can be expressed in general cells, which do not express RV-P protein. The ability of RVΔP-LCMV/GPC to protect mice from LCMV infection and induce cellular immunity was assessed. Mice inoculated intraperitoneally with RVΔP-LCMV/GPC showed higher survival rates (88.2%) than those inoculated with the parental recombinant RV-P gene-deficient RV (RVΔP) (7.7%) following a LCMV challenge. Neutralizing antibody (NAb) against LCMV was not induced, even in the sera of surviving mice. CD8+ T-cell depletion significantly reduced the survival rates of RVΔP-LCMV/GPC-inoculated mice after the LCMV challenge. These results suggest that CD8+ T cells play a major role in the observed protection against LCMV. In contrast, NAbs against RV were strongly induced in sera of mice inoculated with either RVΔP-LCMV/GPC or RVΔP. In safety tests, suckling mice inoculated intracerebrally with RVΔP-LCMV/GPC showed no symptoms.

CONCLUSIONS/SIGNIFICANCE

These results show RVΔP-LCMV/GPC might be a promising candidate vaccine with dual efficacy, protecting against both RV and LCMV.

Authors+Show Affiliations

Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan. Division of Global Infectious Diseases, Department of Infection and Epidemiology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan.Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan. Laboratory of Virology and Viral Infections, Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Kyonancho, Musashino-shi, Tokyo, Japan.Faculty of Pharmacy, Yasuda Women's University, Yasuhigashi, Asaminami, Hiroshima, Japan.Department of virology I, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29659579

Citation

Takayama-Ito, Mutsuyo, et al. "Replication-incompetent Rabies Virus Vector Harboring Glycoprotein Gene of Lymphocytic Choriomeningitis Virus (LCMV) Protects Mice From LCMV Challenge." PLoS Neglected Tropical Diseases, vol. 12, no. 4, 2018, pp. e0006398.
Takayama-Ito M, Lim CK, Yamaguchi Y, et al. Replication-incompetent rabies virus vector harboring glycoprotein gene of lymphocytic choriomeningitis virus (LCMV) protects mice from LCMV challenge. PLoS Negl Trop Dis. 2018;12(4):e0006398.
Takayama-Ito, M., Lim, C. K., Yamaguchi, Y., Posadas-Herrera, G., Kato, H., Iizuka, I., Islam, M. T., Morimoto, K., & Saijo, M. (2018). Replication-incompetent rabies virus vector harboring glycoprotein gene of lymphocytic choriomeningitis virus (LCMV) protects mice from LCMV challenge. PLoS Neglected Tropical Diseases, 12(4), e0006398. https://doi.org/10.1371/journal.pntd.0006398
Takayama-Ito M, et al. Replication-incompetent Rabies Virus Vector Harboring Glycoprotein Gene of Lymphocytic Choriomeningitis Virus (LCMV) Protects Mice From LCMV Challenge. PLoS Negl Trop Dis. 2018;12(4):e0006398. PubMed PMID: 29659579.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Replication-incompetent rabies virus vector harboring glycoprotein gene of lymphocytic choriomeningitis virus (LCMV) protects mice from LCMV challenge. AU - Takayama-Ito,Mutsuyo, AU - Lim,Chang-Kweng, AU - Yamaguchi,Yukie, AU - Posadas-Herrera,Guillermo, AU - Kato,Hirofumi, AU - Iizuka,Itoe, AU - Islam,Md Taimur, AU - Morimoto,Kinjiro, AU - Saijo,Masayuki, Y1 - 2018/04/16/ PY - 2017/08/03/received PY - 2018/03/21/accepted PY - 2018/4/17/entrez PY - 2018/4/17/pubmed PY - 2018/6/21/medline SP - e0006398 EP - e0006398 JF - PLoS neglected tropical diseases JO - PLoS Negl Trop Dis VL - 12 IS - 4 N2 - BACKGROUND: Lymphocytic choriomeningitis virus (LCMV) causes a variety of diseases, including asymptomatic infections, meningitis, and congenital infections in the fetus of infected mother. The development of a safe and effective vaccine against LCMV is imperative. This study aims to develop a new candidate vaccine against LCMV using a recombinant replication-incompetent rabies virus (RV) vector. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we have generated a recombinant deficient RV expressing the LCMV glycoprotein precursor (GPC) (RVΔP-LCMV/GPC) which is lacking the RV-P gene. RVΔP-LCMV/GPC is able to propagate only in cells expressing the RV-P protein. In contrast, the LCMV-GPC can be expressed in general cells, which do not express RV-P protein. The ability of RVΔP-LCMV/GPC to protect mice from LCMV infection and induce cellular immunity was assessed. Mice inoculated intraperitoneally with RVΔP-LCMV/GPC showed higher survival rates (88.2%) than those inoculated with the parental recombinant RV-P gene-deficient RV (RVΔP) (7.7%) following a LCMV challenge. Neutralizing antibody (NAb) against LCMV was not induced, even in the sera of surviving mice. CD8+ T-cell depletion significantly reduced the survival rates of RVΔP-LCMV/GPC-inoculated mice after the LCMV challenge. These results suggest that CD8+ T cells play a major role in the observed protection against LCMV. In contrast, NAbs against RV were strongly induced in sera of mice inoculated with either RVΔP-LCMV/GPC or RVΔP. In safety tests, suckling mice inoculated intracerebrally with RVΔP-LCMV/GPC showed no symptoms. CONCLUSIONS/SIGNIFICANCE: These results show RVΔP-LCMV/GPC might be a promising candidate vaccine with dual efficacy, protecting against both RV and LCMV. SN - 1935-2735 UR - https://www.unboundmedicine.com/medline/citation/29659579/Replication_incompetent_rabies_virus_vector_harboring_glycoprotein_gene_of_lymphocytic_choriomeningitis_virus__LCMV__protects_mice_from_LCMV_challenge_ L2 - https://dx.plos.org/10.1371/journal.pntd.0006398 DB - PRIME DP - Unbound Medicine ER -