Effect of the V3 Loop Deletion of Envelope Glycoprotein on Cellular Responses and Protection against Challenge with Recombinant Vaccinia Virus Expressing gp160 of Primary Human Immunodeficiency Virus Type 1 Isolates

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 (⌬V3) were evaluated in the HLA-A2/K b transgenic mice. It was demonstrated that vaccines expressing the ⌬V3 mutant of either HIV-1 IIIB or HIV-1 89.6 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 ⌬V3 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 ⌬V3 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.

Characteristics of HIV Type 1 (HIV‐1) Glycoprotein 120envSequences in Mother‐Infant Pairs Infected with HIV‐1 Subtype CRF01_AE

“…Interestingly enough, the N301 glycan site was also found in all maternally transmitted CRF01_AE viruses sequenced in an independent study in Thailand [44]. In addition, several in vitro studies have shown that N301 is associated with both a decrease in the sensitivity of HIV-1 to neutralization by CD4BS antibodies and modulation of the interaction of the HIV-1 envelope with CD4 and chemokine receptors [45][46][47].…”

A Single Injection of Recombinant Measles Virus Vaccines Expressing Human Immunodeficiency Virus (HIV) Type 1 Clade B Envelope Glycoproteins Induces Neutralizing Antibodies and Cellular Immune Responses to HIV

“…The effect was more pronounced against heterologous viruses. This observation suggests that removing the V3 region may have exposed some immunological ele- (37). Hence, V3 loop deletion broadens both humoral and cellular immune responses.…”

Increased Level and Longevity of Protective Immune Responses Induced by DNA Vaccine Expressing the HIV-1 Env Glycoprotein when Combined withIL-21andIL-15Gene Delivery

“…with 2 ϫ 10 7 PFU of vBD3 or vSC8 rVV. Five days later, mice were sacrificed, ovaries removed, homogenized, sonicated, and assayed for vaccinia virus titer by plating serial 10-fold dilutions on human HuTK Ϫ 143B indicator cells, staining with crystal violet and counting plaques at each dilution as described (2). To evaluate the contribution of CD8 ϩ and CD4 ϩ T cells as well as NK cells to the vaccine-induced protection against the vBD3 challenge, gp140⌬CFI HxB2/89.6 -immunized mice were treated i.p.…”

“…The synergistic combination of IL-21 and IL-15 also promoted expansion of CD8 ϩ CD127 ϩ memory T cell pools specific for the subdominant HLA-A2-restricted Env 121-129 epitope (KLTPLCVTL) (2), and has resulted in enhanced CD8 ϩ T cell function that was partially independent of CD4 ϩ T cell help in mediating protection against vBD3 challenge. The interaction between these cytokines also increased Ab-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against Env-expressing target cells predominantly through augmentation of Env-specific IgG Ab levels.…”