Ar. Neurath et al., IMPROBABILITY OF HARMFUL AUTOIMMUNE RESPONSES RESULTING FROM IMMUNIZATION WITH HIV-1 ENVELOPE GLYCOPROTEINS, AIDS research and human retroviruses, 9(12), 1993, pp. 1195-1208
Autoimmunity mediated by cross-reactive antibodies, elicited by HIV-1
envelope glycoproteins gp120/gp160, has been postulated to contribute
to the pathogenesis of AIDS. Partial amino acid sequence homology betw
een gp120/gp160 and several human host proteins, including MHC antigen
s and immunoglobulins, has been perceived as the basis for immunologic
al cross-reactivity. Binding of antibodies from sera of HIV-1-infected
individuals to selected host proteins and/or to synthetic peptides de
rived from them and the inhibitory activity of such sera in assays mea
suring the functional activity of T cells provided apparent support fo
r the autoimmunity hypothesis, which is also relevant to the issue of
safety of anti-HIV-1 vaccines. Considering the possibility that the de
tected autoantibodies may arise for reasons other than antibody respon
ses to gp120/gp160, the immunological cross-reactivity between gp120/g
p160 and the relevant host proteins was investigated using hyperimmune
rabbit anti-gp120/gp160 and monoclonal antibodies. As determined from
dilution end-point comparisons for polyclonal anti-gp120, the cross-r
eactivity of anti-gp120 with CD4 was undetectable (<10(-5)%). The cros
s-reactivity of anti-gp120/gp160 with HLA-I and HLA-II antigens was al
so undetectable (<4 x 10(-4)%) and that with other human proteins repo
rted to have partial sequence homology with gp120/gp41 was less-than-o
r-equal-to 0.013%. Anti-gp120/gp160 did not have detectable inhibitory
effects in functional assays measuring proliferative T cell responses
. Therefore, immunization with gp120/gp160 is unlikely to elicit harmf
ul autoimmune responses.