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Volume 6 Supplement 3

AIDS Vaccine 2009

P04-09. Induction of cross-clade neutralizing antibodies with a prime/boost vaccine strategy focused on a neutralizing epitope

Background

Experiments were designed based on the hypothesis that recombinant vaccine constructs can focus the immune response on shared HIV-1 neutralizing epitopes, and that if not diverted by other biologically irrelevant epitopes, high titers of cross-clade neutralizing antibodies (ccNAbs) will be induced. Indeed, previous experiments showed that when the immune response was focused on V3, ccNAbs were induced (Zolla-Pazner et al, Virology, 2008).

Methods

A prime/boost regimen was used in which rabbits were primed (3×) with clade C gp120 DNA and boosted (2×) with: 1) a fusion protein in which the consensus clade C V3 sequence was fused to the C-terminus of MuLV gp70 (V3-gp70), or 2) the same V3 sequence was inserted into a structurally compatible site on cholera toxin B (V3-CTB). Sera were tested for neutralizing activity in TZM-bl cells against a panel of primary isolates and a selection of Tier 1, Tier 2 clade B, and Tier 2 clade C pseudoviruses (psVs) from the standard panel.

Results

Sera from rabbits boosted with V3-CTB neutralized four primary isolates from clades A, AG and B with higher 50% neutralizing titers (NT50) than sera from V3-gp70-boosted rabbits. For example, sera from all five V3-CTB rabbits neutralized Bx08 (with a geometric mean titer [GMT50] = 1:153) whereas only one of five V3-gp70 rabbit responded (1:11). Similarly, serum titers in response to V3-CTB were greater than those to V3-gp70 against 4/4 Tier 1 clade B and C psVs (GMT50 = 1:188 vs. 1:60 for V3-gp70-immunized rabbits). Tier 2 clade C psVZM109F was also neutralized by sera from V3-CTB rabbits (GMT50 = ~1:20).

Conclusion

A prime/boost vaccine regimen using gp120 DNA and V3-scaffold protein immunogens induced ccNAbs. A newly designed V3-CTB protein boost induced the strongest ccNAb response.

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Correspondence to S Zolla-Pazner.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Zolla-Pazner, S., Kong, X., Cardozo, T. et al. P04-09. Induction of cross-clade neutralizing antibodies with a prime/boost vaccine strategy focused on a neutralizing epitope. Retrovirology 6, P37 (2009). https://doi.org/10.1186/1742-4690-6-S3-P37

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Keywords

  • Cholera
  • Cholera Toxin
  • Neutralize Activity
  • Recombinant Vaccine
  • Vaccine Strategy