Mucosal and systemic immune responses to measles virus haemagglutinin in mice immunized with a recombinant vaccinia virus

ABSTRACT We previously showed that envelope (gp160)-based vaccines, used in a live recombinant virus priming and subunit protein boosting regimen, protected macaques against intravenous and intrarectal challenges with the homologous simian immunodeficiency virus SIVmne clone E11S. However, the breadth of protection appears to be limited, since the vaccines were only partially effective against intravenous challenge by the uncloned SIVmne. To examine factors that could affect the breadth and the efficacy of this immunization approach, we studied (i) the effect of priming by recombinant vaccinia virus; (ii) the role of surface antigen gp130; and (iii) the role of core antigens (Gag and Pol) in eliciting protective immunity. Results indicate that (i) priming with recombinant vaccinia virus was more effective than subunit antigen in eliciting protective responses; (ii) while both gp130 and gp160 elicited similar levels of SIV-specific antibodies, gp130 was not as effective as gp160 in protection, indicating a possible role for the transmembrane protein in presenting functionally important epitopes; and (iii) although animals immunized with core antigens failed to generate any neutralizing antibody and were infected upon challenge, their virus load was 50- to 100-fold lower than that of the controls, suggesting the importance of cellular immunity or other core-specific immune responses in controlling acute infection. Complete protection against intravenous infection by the pathogenic uncloned SIVmne was achieved by immunization with both the envelope and the core antigens. These results indicate that immune responses to both antigens may contribute to protection and thus argue for the inclusion of multiple antigens in recombinant vaccine designs.

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Long-term protective immunity to rinderpest in cattle following a single vaccination with a recombinant vaccinia virus expressing the virus haemagglutinin protein

Journal of General Virology ◽

10.1099/0022-1317-81-6-1439 ◽

2000 ◽

Vol 81 (6) ◽

pp. 1439-1446 ◽

Cited By ~ 22

Author(s):

Kazue Ohishi ◽

Kenjiro Inui ◽

Kazuya Yamanouchi ◽

Thomas Barrett

Keyword(s):

Vaccinia Virus ◽

Protective Immunity ◽

Recombinant Vaccinia Virus ◽

Recombinant Vaccinia ◽

Single Vaccination ◽

Virus Haemagglutinin

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Robust HIV-specific immune responses were induced by DNA vaccine prime followed by attenuated recombinant vaccinia virus (LC16m8 strain) boost

Clinical Immunology ◽

10.1016/j.clim.2005.12.007 ◽

2006 ◽

Vol 119 (1) ◽

pp. 32-37 ◽

Cited By ~ 4

Author(s):

Kaori Shinoda ◽

Ke-Qin Xin ◽

Yoshitsugu Kojima ◽

Sukumar Saha ◽

Kentaro Okuda ◽

...

Keyword(s):

Immune Responses ◽

Vaccinia Virus ◽

Dna Vaccine ◽

Recombinant Vaccinia Virus ◽

Recombinant Vaccinia

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Isolate- and Group-Specific Immune Responses to the Envelope Protein of Human Immunodeficiency Virus Induced by a Live Recombinant Vaccinia Virus in Macaques

AIDS Research and Human Retroviruses ◽

10.1089/aid.1989.5.23 ◽

1989 ◽

Vol 5 (1) ◽

pp. 23-32 ◽

Cited By ~ 21

Author(s):

PATRICIA L. EARL ◽

MARJORIE ROBERT-GUROFF ◽

THOMAS J. MATTHEWS ◽

KAI KROHN ◽

WILLIAM T. LONDON ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Responses ◽

Vaccinia Virus ◽

Envelope Protein ◽

Recombinant Vaccinia Virus ◽

Recombinant Vaccinia ◽

Immunodeficiency Virus

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Dendritic cells pulsed with hepatitis C virus NS3 protein induce immune responses and protection from infection with recombinant vaccinia virus expressing NS3

Journal of General Virology ◽

10.1099/vir.0.81423-0 ◽

2006 ◽

Vol 87 (1) ◽

pp. 1-10 ◽

Cited By ~ 19

Author(s):

Hong Yu ◽

Hui Huang ◽

Jim Xiang ◽

Lorne A. Babiuk ◽

Sylvia van Drunen Littel-van den Hurk

Keyword(s):

Dendritic Cells ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Immune Responses ◽

Vaccinia Virus ◽

Recombinant Vaccinia Virus ◽

Interleukin 12 ◽

Cpg Odn ◽

Recombinant Vaccinia ◽

Ns3 Protein

Infections with Hepatitis C virus (HCV) pose a serious health problem worldwide. In this study, the hypothesis that adoptive transfer of dendritic cells (DCs) pulsed with HCV NS3 protein and matured with an oligodeoxynucleotide (ODN) containing CpG motifs (CpG) ex vivo would initiate potent HCV-specific protective immune responses in vivo was tested. NS3 protein was efficiently transduced into DCs and treatment of DCs with CpG ODN induced phenotypic maturation and specifically increased the expression of CD40. DCs matured with CpG ODN produced higher interleukin 12 levels and a stronger allogeneic T-cell response compared with untreated DCs. Notably, there were no differences between NS3-pulsed DCs and DCs pulsed with a control protein with respect to phenotype, cytokine production or mixed lymphocyte reaction, indicating that transduction with NS3 protein did not impair DC functions. Compared with the untreated NS3-pulsed DCs, the NS3-pulsed DCs matured with CpG ODN induced stronger cellular immune responses including enhanced cytotoxicity, higher interferon-γ production and stronger lymphocyte proliferation. Upon challenge with a recombinant vaccinia virus expressing NS3, all mice immunized with NS3-pulsed DCs showed a significant reduction in vaccinia virus titres when compared with mock-immunized mice. However, the NS3-pulsed DCs matured with CpG ODN induced higher levels of protection compared with the untreated NS3-pulsed DCs. These data are the first to show that NS3-pulsed DCs induce specific immune responses and provide protection from viral challenge, and also demonstrate that CpG ODNs, which have a proven safety profile, would be useful in the development of DC vaccines.

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Oral Immunization with Recombinant Vaccinia Virus Prime and Intramuscular Protein Boost Provides Protection against Intrarectal Simian-Human Immunodeficiency Virus Challenge in Macaques

Clinical and Vaccine Immunology ◽

10.1128/cvi.00597-15 ◽

2015 ◽

Vol 23 (3) ◽

pp. 204-212 ◽

Cited By ~ 7

Author(s):

Rajesh Thippeshappa ◽

Baoping Tian ◽

Brad Cleveland ◽

Wenjin Guo ◽

Patricia Polacino ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Immune Responses ◽

Vaccinia Virus ◽

Protective Efficacy ◽

Recombinant Vaccinia Virus ◽

Oral Immunization ◽

Recombinant Vaccinia ◽

Immunodeficiency Virus ◽

Vaccinia Viruses ◽

Hiv 1

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1) acquisition occurs predominantly through mucosal transmission. We hypothesized that greater mucosal immune responses and protective efficacy against mucosal HIV-1 infection may be achieved by prime-boost immunization at mucosal sites. We used a macaque model to determine the safety, immunogenicity, and protective efficacy of orally delivered, replication-competent but attenuated recombinant vaccinia viruses expressing full-length HIV-1 SF162 envelope (Env) or simian immunodeficiency virus (SIV) Gag-Pol proteins. We examined the dose and route that are suitable for oral immunization with recombinant vaccinia viruses. We showed that sublingual inoculation of two vaccinia virus-naive pigtailed macaques with 5 × 108PFU of recombinant vaccinia viruses was safe. However, sublingual inoculation with a higher dose or tonsillar inoculation resulted in secondary oral lesions, indicating the need to optimize the dose and route for oral immunization with replication-competent vaccinia virus vectors. Oral priming alone elicited antibody responses to vaccinia virus and to the SF162 Env protein. Intramuscular immunization with the SF162 gp120 protein at either 20 or 21 weeks postpriming resulted in a significant boost in antibody responses in both systemic and mucosal compartments. Furthermore, we showed that immune responses induced by recombinant vaccinia virus priming and intramuscular protein boosting provided protection against intrarectal challenge with the simian-human immunodeficiency virus SHIV-SF162-P4.

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