Increased immunogenicity of HIV envelope subunit complexed with α2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF
2002; Elsevier BV; Volume: 20; Issue: 17-18 Linguagem: Inglês
10.1016/s0264-410x(02)00090-7
ISSN1873-2518
AutoresHua-Xin Liao, George J. Cianciolo, Herman F. Staats, Richard M. Scearce, Dana M. Lapple, Stephen H. Stauffer, James R. Thomasch, Salvatore V. Pizzo, David C. Montefiori, Michael Hagen, John H. Eldridge, Barton F. Haynes,
Tópico(s)Immunotherapy and Immune Responses
ResumoCritical to the success of HIV-1 subunit vaccines is the development of strategies to augment vaccine immunogenicity. Successful adjuvants must not only improve immunogenicity above current adjuvant levels, but must also decrease the dose of immunogen required for optimal immunogenicity. We have evaluated activated α2-macroglobulin (α2M∗) and a squalene-based stable emulsion containing monophosphoryl lipid A (MPL-SE) with granulocyte-macrophage colony stimulating factor (GM-CSF) as adjuvants to enhance the immunogencity of candidate HIV immunogens. Balb/c mice were subcutaneously immunized on days 0, 14 and 28 with 100–0.1 μg of HIV-1 envelope gp120 C4–V3 immunogens from either HIV IIIB (C4–V3IIIB) or SHIV 89.6P (C4–V389.6P). Immunogens were tested covalently coupled to α2M∗, formulated with MPL-SE/GM-CSF, or as a combination of both. Using CFA/IFA, only 50 and 100 μg, but not lower doses of C4–V3IIIB peptides, induced antibody responses. In contrast, peak antibody responses were detected in mice immunized with 10 μg of C4–V3 peptide coupled to α2M∗ (α2M∗-peptide). Similar to CFA/IFA, MPL-SE/GM-CSF induced optimal antibody responses at 50 and 100 μg of C4–V3 immunogen. However, the combination of MPL-SE/GM-CSF with α2M∗-C4–V3 peptide decreased the dose of C4–V3 required for optimal response to 5 μg for C4–V3IIIB, and to 0.1 μg for C4–V389.6P. Taken together, HIV envelope gp120 C4–V3 peptides covalently complexed with α2M∗ and formulated with MPL-SE/GM-CSF resulted in a subunit HIV immunogen capable of inducing anti-HIV envelope antibody responses at doses up to100-fold less than those needed with CFA/IFA or MPL-SE/GM-CSF alone.
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