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Volume 6 Supplement 3

AIDS Vaccine 2009

P04-02. Increased breadth and potency of the neutralizing antibody response among dually-HIV-1-infected individuals

Background

Neutralizing antibodies (nAbs) generated during HIV-1 infection are insufficient to protect against a 2nd (dual) infection; yet, little is known regarding the effect of a 2nd infection on the anti-HIV-1 nAb response. Therefore, the objective of this study was to analyze the effect of dual infection by subtype-discordant HIV-1 strains on the potency and breadth of this nAb response.

Methods

Two sequential plasma samples from 4 dually-intersubtype-infected subjects, obtained ~6 months before and >12 months after the 2nd infection was identified, were tested against 7 heterologous viruses (5 primary isolates and 2 Tier1 viruses) representing subtypes A1, B, F2, G, and CRF02_AG in the GHOST cell neutralization assay. Additionally, 23 singly-infected control subjects matched for disease stage, CD4 counts, and time between samples were studied. Plasma was assayed at 1:80 dilution to compare each plasma pair; subsequently, plasma from dually-infected subjects and 6 control subjects were assessed for magnitude and specificity of neutralization using plasma serial dilutions, 1:20–1:640.

Results

At 1:80 plasma dilution, 3 of the 4 dually-infected subjects' plasma obtained after dual infection exhibited significantly increased neutralization compared to initial plasma. Increases in percent neutralization for all 3 plasma pairs against all 7 heterologous viruses were significant (0.05 > p > 0.001), with the 2nd sample exhibiting 65%–96% neutralization. No control plasmas exhibited >30% neutralization of any of the heterologous viruses; thus, there was an overall significant difference between case and control subject-sets (p = 0.009). Fifty percent neutralization titers (IC50) of plasma obtained after dual infection from the 3 dually-infected subjects exhibited ~6X–100X increases compared to the initial samples (0.05 > p > 0.0001). No differences in the magnitudes of neutralization were observed for any of the singly-infected, control sample pairs.

Conclusion

These data propose that re-infection by a subtype-discordant virus broadens the anti-HIV-1 immune response, suggesting that vaccines incorporating and/or boosting with subtype-discordant immunogens may generate significantly improved anti-HIV-1 immunity.

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Correspondence to RL Powell.

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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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Powell, R., Kinge, T. & Nyambi, P. P04-02. Increased breadth and potency of the neutralizing antibody response among dually-HIV-1-infected individuals. Retrovirology 6, P30 (2009). https://doi.org/10.1186/1742-4690-6-S3-P30

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Keywords

  • Ghost Cell
  • Neutralization Assay
  • Dual Infection
  • Initial Plasma
  • Primary Isolate