Immunization of mice with peptomers covalently coupled to aluminum oxide nanoparticles.
Subunit vaccines generally require adjuvants to elicit immune responses, but adjuvants may alter the conformation of critical epitopes and reduce vaccine 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 alpha-helical conformation prior to binding to CD4. Immune responses in mice to peptomer-nanoparticle conjugates were compared to responses elicited by free C4 peptide and C4 peptomers, with and without the hydrophilic adjuvant muramyl 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, glycosylated gp120 and HIV-1 infected T cells. The results suggest that this novel vaccine approach could be useful for induction of immune responses against conformation-sensitive viral antigens without the need for additional adjuvants.
Frey
A
A
Children's Hospital, Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
Mantis
N
N
Kozlowski
P A
PA
Quayle
A J
AJ
Bajardi
A
A
Perdomo
J J
JJ
Robey
F A
FA
Neutra
M R
MR
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D000537:Aluminum Oxide / Q000008:administration & dosage / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D000918:Antibody Specificity; D015704:CD4 Antigens / Q000276:immunology / Q000378:metabolism; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D010316:Particle Size; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology
D016915:AIDS Vaccines; D015704:CD4 Antigens; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D010446:Peptide Fragments; D000537:Aluminum Oxide