B7 co-stimulatory requirements differ for induction of immune responses by DNA, protein and recombinant pox virus vaccination

Abstract

Whether B7‐1 and B7‐2 have distinct functions for eliciting immune responses to antigens that are presented to the immune system by intracellular and extracellular antigen processing pathways is an unresolved question. To investigate this issue we compared the humoral and cellular immune responses elicited by immunizing wild‐type, B7‐1– / – and B7‐2– / – mice with either HIV‐1 gp120 plasmid DNA, recombinant gp120 protein or vaccinia virus expressing gp120. The generation of both humoral and cellular immune responses to an antigen produced intracellularly following DNA vaccination had critical requirements for B7‐2, but not B7‐1. Neither of the molecules was essential for the generation of antibody responses to an extracellular protein antigen administered with adjuvant; B7‐1 had little effect on the elicited immune responses. When recombinant vaccinia virus was used to present antigen intracellularly in the context of a viral infection, B7‐2 was absolutely required for antibody and T cell proliferative responses, but it exerted a suppressive effect on the elicited CTL activity. These results demonstrate that antigens presented to the immune system by different mechanisms have distinct B7‐1 and B7‐2 co‐stimulatory requirements.

Ag85B of Mycobacteria Elicits Effective CTL Responses through Activation of Robust Th1 Immunity as a Novel Adjuvant in DNA Vaccine

“…Activation of CD4 ϩ T cells is required for maturation of DCs through CD40 signaling (3)(4)(5); however, this requirement is not sufficient in many cases of DNA vaccine immunization (25,26). Various studies on compensation for the insufficiency of CD4 ϩ T cell help by coadministration of costimulatory molecules, such as B7-1 or B7-2 (27,28), or by treatment with a CD40 agonist during immunization have therefore been conducted (26). Another CD4 ϩ T cell-mediated helper effect for induction of CTL by DNA vaccine is thought to be the production of cytokines for enhancement of activity and proliferation of CTLs (29).…”

Functional Equivalency of B7-1 and B7-2 for Costimulating Plasmid DNA Vaccine-Elicited CTL Responses

“…The sham plasmid was the empty pV1J vector. Plasmidencoded B7-1 and B7-2 were constructed in the pV1J backbone, as described previously (25). Plasmids were prepared from large-scale bacterial cultures, as described elsewhere (24).…”

“…CTL responses specific for the immunodominant gp120 P18 peptide (26) were assessed in vaccinated mice, as reported previously (24,25). Spleens were aseptically removed 3 wk after immunization, and RBC were removed from single-cell splenocyte suspensions using a hypotonic NH 4 ClKCl lysis buffer.…”

“…This observation extends our previous findings that B7-1 and B7-2 are largely overlapping in function. B7-1 Ϫ/Ϫ mice and B7-2 Ϫ/Ϫ mice both can generate Ab responses to protein Ags administered with adjuvant, as well as Ab and CTL responses to vesicular stomatitis virus and recombinant vaccinia virus infection (16,17,25). However, B7-2 Ϫ/Ϫ mice cannot generate effective immune responses to protein Ags administered without adjuvant or following plasmid DNA vaccination, suggesting that B7-2 may be critical for the initiation of these immune responses (16,25).…”

“…B7-1 Ϫ/Ϫ mice and B7-2 Ϫ/Ϫ mice both can generate Ab responses to protein Ags administered with adjuvant, as well as Ab and CTL responses to vesicular stomatitis virus and recombinant vaccinia virus infection (16,17,25). However, B7-2 Ϫ/Ϫ mice cannot generate effective immune responses to protein Ags administered without adjuvant or following plasmid DNA vaccination, suggesting that B7-2 may be critical for the initiation of these immune responses (16,25). It has been suggested that adjuvants and viral infections lead to a rapid up-regulation of B7-1 expression that can compensate for an absence of B7-2, and that the requirement for B7-2 for generating immune responses in the absence of adjuvant reflects its constitutive expression on APCs.…”