Subunit vaccines generally require adjuvants to elicit immune responses, bu
t adjuvants may alter the conformation of critical epitopes and reduce vacc
ine efficacy. We therefore tested an immunization strategy in which antigen
is covalently coupled to aluminum oxide nanoparticles using a method that
favors preservation of the native conformation. The test antigen consisted
of "peptomers" (head-to-tail-linked peptide homopolymers) derived from the
4th conserved region (C4) of HIV-1 gp120 which is believed to be in an alph
a-helical conformation prior to binding to CD4, Immune responses in mice to
peptomer-nanoparticle conjugates were compared to responses elicited by fr
ee C4 peptide and C4 peptomers, with and without the hydrophilic adjuvant m
uramyl dipeptide (MDP). Highest peptomer-specific serum antibody responses
were induced by peptomer-particles without MDP. Serum antibodies induced by
peptomer-particles also showed highest reactivity towards recombinant, gly
cosylated gp120 and HIV-1 infected T cells. The results suggest that this n
ovel vaccine approach could be useful for induction of immune responses aga
inst conformation-sensitive viral antigens without the need for additional
adjuvants. (C) 1999 Elsevier Science Ltd. All rights reserved.