Polyvalent human immunodeficiency virus synthetic immunogen comprised of envelope gp120 T helper cell sites and B cell neutralization epitopes.
In previous studies, we have used antisera raised to envelope (env)-gene-encoded synthetic peptides to identify a region of (HIV) glycoprotein (gp) 120 env protein designated SP10 that contains a type-specific neutralizing determinant. To develop a polyvalent, synthetic peptide inoculum that can evoke both neutralizing antibodies and T cell proliferative responses to more than one HIV isolate, synthetic peptides containing type-specific neutralizing determinants of gp120 from HIV isolates HTLV-IIIB (IIIB), HTLV-IIIMN (MN) and HTLV-IIIRF (RF) were coupled to a 16 amino acid T cell epitope (T1) of HIV-IIIB gp120 and used to immunize goats. Goat antisera to each T1-SP10 peptide derived from the SP10 region of gp120 of IIIB, MN, and RF neutralized HIV isolates IIIB, MN and RF in a type-specific manner. Moreover, peripheral blood T cells from immunized goats also proliferated in a type-specific manner to peptides derived from gp120 of IIIB, MN, and RF. When combined in a trivalent inoculum, T1-SP10 peptides from HIV-1 isolates IIIB, MN, and RF evoked a high titered neutralizing antibody response to isolates IIIB, MN, and RF in goats and as well induced immune T cells to undergo blast transformation in the presence of peptides derived from gp120 of all three HIV isolates. The T1 portion of the T1-SP10 construct was shown to induce a B cell antibody response against determinants within the T1 peptide in addition to inducing T cell proliferative responses in immune goat T cells. Moreover, the SP10 portion of the T1-SP10 constructs not only induced B cell antibody production but also induced type-specific T cell proliferative responses localized to the C-terminal variable sequences of the SP10 peptides. Finally, the T1-SP10 peptide construct induced memory T cell proliferative responses to native gp120 env protein. Thus, combinations of homologous SP10 region synthetic peptides containing type-specific neutralizing determinants and T cell epitopes of HIV gp120 may be useful in man to elicit high titered neutralizing B cell responses and, as well, T cell responses to more than one HIV isolate.
Palker
T J
TJ
Department of Medicine, Duke University Medical Center, Durham, NC 27710.
Matthews
T J
TJ
Langlois
A
A
Tanner
M E
ME
Martin
M E
ME
Scearce
R M
RM
Kim
J E
JE
Berzofsky
J A
JA
Bolognesi
D P
DP
Haynes
B F
BF
D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000956:Antigens, Viral / Q000032:analysis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D000939:Epitopes / Q000032:analysis / Q000276:immunology; D006041:Goats; D006678:HIV / Q000276:immunology* / Q000302:isolation & purification; D015699:HIV Envelope Protein gp120; D007106:Immune Sera; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D011994:Recombinant Proteins / Q000032:analysis / Q000276:immunology*; D012191:Retroviridae Proteins / Q000032:analysis / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D015699:HIV Envelope Protein gp120; D007106:Immune Sera; D010446:Peptide Fragments; D011994:Recombinant Proteins; D012191:Retroviridae Proteins