scholarly journals Accelerated Viremia in Cats Vaccinated with Recombinant Vaccinia Virus Expressing Envelope Glycoprotein of Feline Immunodeficiency Virus

1996 ◽  
Vol 12 (5) ◽  
pp. 437-441 ◽  
Author(s):  
ALBERT D.M.E. OSTERHAUS ◽  
EDWIN TIJHAAR ◽  
ROBIN C. HUISMAN ◽  
WILLEM HUISMAN ◽  
IAN H. DARBY ◽  
...  
2002 ◽  
Vol 76 (9) ◽  
pp. 4222-4232 ◽  
Author(s):  
Irena Kiszka ◽  
Dariusz Kmieciak ◽  
Jaroslaw Gzyl ◽  
Toshio Naito ◽  
Elizabeth Bolesta ◽  
...  

ABSTRACT The magnitude and breadth of cytotoxic-T-lymphocyte (CTL) responses induced by human immunodeficiency virus type 1 (HIV-1) envelope protein from which the hypervariable V3 loop had been deleted (ΔV3) were evaluated in the HLA-A2/Kb transgenic mice. It was demonstrated that vaccines expressing the ΔV3 mutant of either HIV-1IIIB or HIV-189.6 envelope glycoprotein induced broader CD8+ T-cell activities than those elicited by the wild-type (WT) counterparts. Specifically, the differences were associated with higher responses to conserved HLA-A2-restricted CTL epitopes of the envelope glycoprotein and could be correlated with an increased cell surface occupancy by the epitope-HLA-A2 complexes in target cells expressing the ΔV3 mutant. Using recombinant vaccinia virus expressing heterologous gp160 of primary HIV-1 isolates in a murine challenge system, we observed that the extent of resistance to viral transmission was higher in animals immunized with the ΔV3 than the WT envelope vaccine. The protection was linked to the presence of envelope-specific CD8+ T cells, since depletion of these cells by anti-CD8 antibody treatment at the time of challenge abolished the vaccine-induced protection. The results from our studies provide insights into approaches for boosting the breadth of envelope-specific CTL responses.


1993 ◽  
Vol 30 (2) ◽  
pp. 104-110 ◽  
Author(s):  
K. Okada ◽  
S. Ikeyama ◽  
K. Ohishi ◽  
H. Suzuki ◽  
M. Sugimoto ◽  
...  

Delayed-type hypersensitivity responses against bovine leukemia virus (BLV) envelope glycoprotein (gp60) were induced in the skin of sheep vaccinated with recombinant vaccinia virus (RVV) expressing BLV glycoprotein. The lesions were characterized by marked infiltration of lymphocytes, slight migration of neutrophils, eosinophils, and macrophages in the dermis to hypodermis, and partial intercellular edema in the reticular layer. Immunohistochemical analysis with monoclonal antibodies demonstrated that the lymphocytic infiltrates consisted mainly of CD8+ T cells (53.7–55.8% at 48 hours post-challenge of BLV), CD4+ T cells (24.7–26.7%), and B cells (11.5–16.9%). The role of CD4+ and CD8+ T cells in suppressing BLV growth in RVV-vaccinated animals is discussed.


1999 ◽  
Vol 73 (10) ◽  
pp. 8201-8215 ◽  
Author(s):  
Patricia S. Polacino ◽  
Virginia Stallard ◽  
James E. Klaniecki ◽  
Sridhar Pennathur ◽  
David C. Montefiori ◽  
...  

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.


1998 ◽  
Vol 72 (10) ◽  
pp. 8264-8272 ◽  
Author(s):  
Igor M. Belyakov ◽  
Linda S. Wyatt ◽  
Jeffrey D. Ahlers ◽  
Patricia Earl ◽  
C. David Pendleton ◽  
...  

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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