scholarly journals Role of Immune Responses against the Envelope and the Core Antigens of Simian Immunodeficiency Virus SIVmne in Protection against Homologous Cloned and Uncloned Virus Challenge in Macaques

1999 ◽  
Vol 73 (10) ◽  
pp. 8201-8215 ◽  
Author(s):  
Patricia S. Polacino ◽  
Virginia Stallard ◽  
James E. Klaniecki ◽  
Sridhar Pennathur ◽  
David C. Montefiori ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
Simian Immunodeficiency Virus ◽  
Transmembrane Protein ◽  
Acute Infection ◽  
Recombinant Vaccinia Virus ◽  
Recombinant Vaccinia ◽  
The Core ◽  
Immunodeficiency 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.

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

2015 ◽  
Vol 23 (3) ◽  
pp. 204-212 ◽  
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.

High-Titer Immune Responses Elicited by Recombinant Vaccinia Virus Priming and Particle Boosting Are Ineffective in Preventing Virulent SIV Infection

1994 ◽  
Vol 10 (7) ◽  
pp. 839-851 ◽  
Author(s):  
MUTHIAH D. DANIEL ◽  
GAIL P. MAZZARA ◽  
MEREDITH A. SIMON ◽  
PRABHAT K. SEHGAL ◽  
TOSHIAKI KODAMA ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccinia Virus ◽  
High Titer ◽  
Recombinant Vaccinia Virus ◽  
Recombinant Vaccinia ◽  
Siv Infection

scholarly journals Induction of a Mucosal Cytotoxic T-Lymphocyte Response by Intrarectal Immunization with a Replication-Deficient Recombinant Vaccinia Virus Expressing Human Immunodeficiency Virus 89.6 Envelope Protein

1998 ◽  
Vol 72 (10) ◽  
pp. 8264-8272 ◽  
Author(s):  
Igor M. Belyakov ◽  
Linda S. Wyatt ◽  
Jeffrey D. Ahlers ◽  
Patricia Earl ◽  
C. David Pendleton ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Vaccinia Virus ◽  
T Lymphocyte ◽  
Envelope Protein ◽  
Cytotoxic T Lymphocyte ◽  
Recombinant Vaccinia Virus ◽  
Mucosal Immunization ◽  
Recombinant Vaccinia ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT To improve the safety of recombinant vaccinia virus vaccines, modified vaccinia virus Ankara (MVA) has been employed, because it has a replication defect in most mammalian cells. Here we apply MVA to human immunodeficiency virus type 1 (HIV-1) vaccine development by incorporating the envelope protein gp160 of HIV-1 primary isolate strain 89.6 (MVA 89.6) and use it to induce mucosal cytotoxic-T-lymphocyte (CTL) immunity. In initial studies to define a dominant CTL epitope for HIV-1 89.6 gp160, we mapped the epitope to a sequence, IGPGRAFYAR (from the V3 loop), homologous to that recognized by HIV MN loop-specific CTL and showed that HIV-1 MN-specific CTLs cross-reactively recognize the corresponding epitope from strain 89.6 presented by H-2Dd. Having defined the CTL specificity, we immunized BALB/c mice intrarectally with recombinant MVA 89.6. A single mucosal immunization with MVA 89.6 was able to elicit long-lasting antigen-specific mucosal (Peyer’s patch and lamina propria) and systemic (spleen) CTL responses as effective as or more effective than those of a replication-competent vaccinia virus expressing 89.6 gp160. Immunization with MVA 89.6 led to (i) the loading of antigen-presenting cells in vivo, as measured by the ex vivo active presentation of the P18-89.6 peptide to an antigen-specific CTL line, and (ii) the significant production of the proinflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) in the mucosal sites. These results indicate that nonreplicating recombinant MVA may be at least as effective for mucosal immunization as replicating recombinant vaccinia virus.

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