p04-11. prevalence of neutralizing antibody responses in chronic clades a and d human...

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BioMed Central Page 1 of 1 (page number not for citation purposes) Retrovirology Open Access Poster presentation P04-11. Prevalence of neutralizing antibody responses in chronic clades A and D human immunodeficiency virus type 1 (HIV-1) infections HF Njai* 1 , K Tomusange 1 , B Sokolik-Wolak 2 , D Montefiori 2 , S Balla 3 , G Vanham 3 , J Levin 1 , D Maher 1 , A Kamali 1 , H Grosskurth 1 , P Pala 1 and P Kaleebu 1 Address: 1 Basic Science Department, MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda, 2 Laboratory for AIDS Research & Development, Duke University, Durham, NC, USA and 3 Institute of Tropical Medicine, Antwerp, Belgium * Corresponding author Background Characterizing neutralizing antibody (Nab) responses in non-B HIV-1 subtypes is essential, because the data may illustrate key genetic and antibody properties that could impact the design and testing of Nab vaccine candidates in countries where these subtypes circulate. The principle objective of this study is to document the magnitude, breadth and prevalence of neutralizing antibodies in a cohort of non-B HIV chronically infected individuals in rural Uganda. Methods 45 treatment naive patients were randomly selected from the Rural Clinical Cohort (RCC), which recruits HIV infected individuals with known date of sero-conversion. The average time of infection was 5.45 yrs (range 1–16 yrs). Two sample points were selected for each patient; T1(early) and T2(late), and tested against two tier-1 strains of HIV-1 (SF162.LS, MW965.26) and MLV nega- tive control virus; in the standardized TZM-bl neutraliza- tion assay. MLV positive samples were excluded from analaysis. Results Magnitude of the NAb response against SF162.LS(subtype B) and MW965.26(subtype C) varied but was relatively potent in a most cases (ID50 titers >1,000, range 20– 87,480). 30% of samples showed activity against SF162 at T1 and 40% against MW965.26. At T2, a significant increase in titers against both viruses was observed; 50% neutralized SF162 and 65% neutralized MW965.26 (p = 0.001 and p = 0.0006 respectively). NAb titers against both viruses were closely associated and increased signifi- cantly (p <0.0012) from the early to late time point. The magnitude of this increase was substantial in some sub- jects, whereas in a few the response decreased over time. Conclusion A high prevalence of Nabs was detected. The magnitude and long-term kinetics varied between subjects. Further analysis with tier 2 viruses (4 As, 4 Bs, 4 Cs and 4 Ds) and association with viral load and CD4 counts will be per- formed to document the prevalence and kinetics of cross- reactive neutralizing antibody responses. from AIDS Vaccine 2009 Paris, France. 19–22 October 2009 Published: 22 October 2009 Retrovirology 2009, 6(Suppl 3):P39 doi:10.1186/1742-4690-6-S3-P39 <supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement> This abstract is available from: http://www.retrovirology.com/content/6/S3/P39 © 2009 Njai et al; licensee BioMed Central Ltd.

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BioMed Central

Page 1 of 1(page number not for citation purposes)

Retrovirology

Open AccessPoster presentationP04-11. Prevalence of neutralizing antibody responses in chronic clades A and D human immunodeficiency virus type 1 (HIV-1) infectionsHF Njai*1, K Tomusange1, B Sokolik-Wolak2, D Montefiori2, S Balla3, G Vanham3, J Levin1, D Maher1, A Kamali1, H Grosskurth1, P Pala1 and P Kaleebu1

Address: 1Basic Science Department, MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda, 2Laboratory for AIDS Research & Development, Duke University, Durham, NC, USA and 3Institute of Tropical Medicine, Antwerp, Belgium

* Corresponding author

BackgroundCharacterizing neutralizing antibody (Nab) responses innon-B HIV-1 subtypes is essential, because the data mayillustrate key genetic and antibody properties that couldimpact the design and testing of Nab vaccine candidatesin countries where these subtypes circulate. The principleobjective of this study is to document the magnitude,breadth and prevalence of neutralizing antibodies in acohort of non-B HIV chronically infected individuals inrural Uganda.

Methods45 treatment naive patients were randomly selected fromthe Rural Clinical Cohort (RCC), which recruits HIVinfected individuals with known date of sero-conversion.The average time of infection was 5.45 yrs (range 1–16yrs). Two sample points were selected for each patient;T1(early) and T2(late), and tested against two tier-1strains of HIV-1 (SF162.LS, MW965.26) and MLV nega-tive control virus; in the standardized TZM-bl neutraliza-tion assay. MLV positive samples were excluded fromanalaysis.

ResultsMagnitude of the NAb response against SF162.LS(subtypeB) and MW965.26(subtype C) varied but was relatively

potent in a most cases (ID50 titers >1,000, range 20–87,480). 30% of samples showed activity against SF162 atT1 and 40% against MW965.26. At T2, a significantincrease in titers against both viruses was observed; 50%neutralized SF162 and 65% neutralized MW965.26 (p =0.001 and p = 0.0006 respectively). NAb titers againstboth viruses were closely associated and increased signifi-cantly (p <0.0012) from the early to late time point. Themagnitude of this increase was substantial in some sub-jects, whereas in a few the response decreased over time.

ConclusionA high prevalence of Nabs was detected. The magnitudeand long-term kinetics varied between subjects. Furtheranalysis with tier 2 viruses (4 As, 4 Bs, 4 Cs and 4 Ds) andassociation with viral load and CD4 counts will be per-formed to document the prevalence and kinetics of cross-reactive neutralizing antibody responses.

from AIDS Vaccine 2009Paris, France. 19–22 October 2009

Published: 22 October 2009

Retrovirology 2009, 6(Suppl 3):P39 doi:10.1186/1742-4690-6-S3-P39

<supplement> <title> <p>AIDS Vaccine 2009</p> </title> <editor>Anna Laura Ross</editor> <note>Meeting abstracts – A single PDF containing all abstracts in this Supplement is available <a href="http://www.biomedcentral.com/content/files/pdf/1742-4690-6-S3-full.pdf">here</a>.</note> <url>http://www.biomedcentral.com/content/pdf/1471-2105-10-S12-info.pdf</url> </supplement>

This abstract is available from: http://www.retrovirology.com/content/6/S3/P39

© 2009 Njai et al; licensee BioMed Central Ltd.