Immunization of mice with peptomers covalently coupled to aluminum oxide nanoparticles

• Published in: Vaccine Vol. 17; no. 23; pp. 3007 - 3019
• Main Authors: Frey, Andreas, Mantis, Nicholas, Kozlowski, Pamela A, Quayle, Alison J, Bajardi, Adriana, Perdomo, Juana J, Robey, Frank A, Neutra, Marian R
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 06.08.1999; Elsevier
• Subjects: Adjuvant; AIDS Vaccines - administration & dosage; AIDS Vaccines - chemistry; AIDS Vaccines - immunology; AIDS Vaccines - metabolism; AIDS/HIV; Aluminum Oxide - administration & dosage; Aluminum Oxide - immunology; Amino Acid Sequence; Animals; Antibodies; Antibody Specificity; Biological and medical sciences; CD4 Antigens - immunology; CD4 Antigens - metabolism; Female; Fundamental and applied biological sciences. Psychology; HIV Antibodies - blood; HIV Envelope Protein gp120 - chemistry; HIV Envelope Protein gp120 - immunology; HIV Envelope Protein gp120 - metabolism; HIV-1 - immunology; Intestinal Mucosa - immunology; Mice; Mice, Inbred BALB C; Microbiology; Molecular Sequence Data; Particle Size; Peptide Fragments - chemistry; Peptide Fragments - immunology; Peptide Fragments - metabolism; T-Lymphocytes - immunology; Vaccine; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies; Virology; i.g., intragastrical(ly); T1, helper T cell antigenic site; i.r., intrarectal(ly); C4, fourth conserved region of HIV-1 gp120; Antibodies; i.n., intranasal(ly); Vaccine; MDP, muramyl dipeptide; MNC, mononuclear cell(s); V2 (3,4,5), second (third, fourth, fifth) variable region of HIV-1 gp120; ANOVA, analysis of variance; Adjuvant; D-PBS, Dulbecco’s PBS; CT, cholera toxin; RT, room temperature; Aluminium oxide; Antigenic determinant; Peptides; HIV-1 virus; Rodentia; Glycoprotein; Retroviridae; Lentivirus; Property formulation relationship; Virus; Vertebrata; Mammalia; Immunogenicity; Mouse; Immunological adjuvant; Covalent bond; Human immunodeficiency virus; Conjugated compound; Humoral immunity
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/S0264-410X(99)00163-2

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 α-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.