Immunomodulatory effects of a plasmid expressing B7‐2 on human immunodeficiency virus‐1‐specific cell‐mediated immunity induced by a plasmid encoding the viral antigen

Abstract

B7 co-stimulation is essential for activating resting T cells following antigen recognition by the T cell receptor. To determine whether B7 has adjuvant activities on human immunodeficiency virus type-1 (HIV-1)-specific immunity induced by inoculation of a plasmid encoding HIV-1 env and rev (DNA vaccine), B7-1 and B7-2 expression plasmids were co-inoculated with the DNA vaccine. The delayed-type hypersensitivity response and cytotoxic T lymphocyte (CTL) activity were significantly enhanced when B7-2 expression plasmid was co-inoculated with the DNA vaccine, but were unaffected when the B7-1 expression plasmid was used with the vaccine instead. The immunological response enhanced by B7-2 decreased below the level of mice immunized with the DNA vaccine in combination with CTLA4Ig, an inhibitor of the B7/CD28 co-stimulatory signal, suggesting that this signal is critical for the enhanced response induced by co-inoculation of the DNA vaccine and B7-2 expression plasmid. This enhancement appeared to occur via an interferon-gamma (IFN-gamma)-dependent mechanism, as combined administration of the B7-2 plasmid and neutralizing anti-IFN-gamma antibody abrogated the virus-specific cell-mediated immunity. These results suggest that this gene-based co-inoculation strategy using HIV-1 viral antigen and B7-2 co-stimulatory molecule could be a powerful means of combating HIV-1 infection.

Use of B7 costimulatory molecules as adjuvants in a prime-boost vaccination against Visna/Maedi ovine lentivirus

“…Likely, these cells underwent clonal expansion and re--distribution in the organism (week 12) and were maintained in a low proportion in blood after virus clearance (weeks 16, 20 and 24). The enhancement of CTL responses when incorporating CD86 into the vaccine is in agreement with a series of previous HIV studies in mice [46], [47] and [48] where inclusion of CD80 in the inoculum did not generate CTL responses. However, the relative role of both CD80 and CD86 molecules remains controversial, as there are studies in mice which either propose the enhancement of both cellular and humoral responses when using CD86 [49] or describe the enhancement of CTL responses when incorporating CD80 rather than CD86 [50].…”

Intracellular adhesion molecule-1 modulates β-chemokines and directly costimulates T cells in vivo

“…These molecules have been examined in the context of DNA vaccines as modulatory agent. In this context, it appears that CD86 molecules play a prominent role in the antigen-specific induction of CD8 + cytotoxic T lymphocytes when delivered as vaccine adjuvants (13,18,19). Coadministration of CD86 cDNA along with DNA immunogens dramatically increased antigen-specific CD8 + CTL response (13).…”

The Timing of GM-CSF Expression Plasmid Administration Influences the Th1/Th2 Response Induced by an HIV-1-Specific DNA Vaccine

“…However, adjuvants may be needed to enhance the immune response elicited by this DNA vaccine. Therefore, we and other groups have been studying the effects of multiple potential adjuvants, including cationic liposomes (6), Ribi adjuvant (7,8), vectamidin (9), QS21 (10), B7-2 (11), IL-2 (12), macrophage inflammatory protein-1␣ (13), IL-12 (11,14,15), TCA3 (16), and others (5).…”