Effects of adjuvants and multiple antigen peptides on humoral and cellular immune responses to gp160 of HIV-1.
The capacity of five different adjuvants, AlPO4, a muramyldipeptide formulation (MDP.TSL), Freund's adjuvant, immunostimulating complex and its matrix components to elicit humoral and cellular responses in rabbits immunized with the human immunodeficiency virus type 1 (HIV-1) envelope protein rgp160IIIB was compared. The highest antibody titers against gp160 and gp41/gp120 epitopes were seen with rgp160 in MDP.TSL or Freund's adjuvant, whereas the broadest responses were seen in rabbits immunized with rgp160 in matrix or MDP.TSL. The broadest spectrum of high-avidity antibodies was also induced by rgp160 in MDP.TSL. Neutralizing titers against HIV-1IIIB, low titers to HIV-1MN, and the most efficient inhibition of viral cell-to-cell spread was seen with rgp160 in MDP.TSL. The strongest and most persisting cellular responses were induced by rgp160 in AlPO4 or MDP.TSL. Using MDP.TSL as the adjuvant, we also improved the immune response against gp120 epitopes by boosting rgp160-primed rabbits with rgp160, multiple antigenic peptides (MAPs), or unconjugated peptides. The MAPs induced high neutralizing titers and were superior to rgp160 alone in inducing both humoral and cellular reactivity. MAPs are therefore strong candidates for inclusion into future HIV-1 vaccines.
Levi
M
M
Department of Virology, National Bacteriological Laboratory, Stockholm, Sweden.
Rudén
U
U
Birx
D
D
Loomis
L
L
Redfield
R
R
Lövgren
K
K
Akerblom
L
L
Sandström
E
E
Wahren
B
B
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000535:Aluminum / Q000494:pharmacology; D017607:Aluminum Compounds; D000595:Amino Acid Sequence; D000818:Animals; D000915:Antibody Affinity; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D015686:Gene Products, env / Q000737:chemistry / Q000276:immunology*; D015483:HIV Antibodies / Q000096:biosynthesis*; D015488:HIV Antigens / Q000737:chemistry / Q000276:immunology*; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D016882:ISCOMs / Q000276:immunology / Q000494:pharmacology; D007111:Immunity, Cellular / Q000187:drug effects; D007114:Immunization; D007117:Immunization, Secondary; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology; D010710:Phosphates / Q000494:pharmacology; D011498:Protein Precursors / Q000737:chemistry / Q000276:immunology*; D011817:Rabbits; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014779:Virus Replication / Q000276:immunology
D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D015686:Gene Products, env; D015483:HIV Antibodies; D015488:HIV Antigens; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D016882:ISCOMs; D010446:Peptide Fragments; D010710:Phosphates; D011498:Protein Precursors; D011994:Recombinant Proteins; D000119:Acetylmuramyl-Alanyl-Isoglutamine; D005620:Freund's Adjuvant; D000535:Aluminum; C012714:aluminum phosphate