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Serum neutralizing activities from a Beijing homosexual male cohort infected with different subtypes of HIV-1 in China.

Zhang M, Jiao Y, Wang S, Zhang L, Huang Z, Chen Y, Wu H - PLoS ONE (2012)

Bottom Line: Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples.Our study confirmed the presence of broadly neutralizing sera in China's HIV-1 patient population.Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Province Key Laboratory in Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT
Protective antibodies play a critical role in an effective HIV vaccine; however, eliciting antibodies to block infection by viruses from diverse genetic subtypes remains a major challenge. As the world's most populous country, China has been under the threat of at least three major subtypes of circulating HIV-1 viruses. Understanding the cross reactivity and specificities of serum antibody responses that mediate broad neutralization of the virus in HIV-1 infected Chinese patients will provide valuable information for the design of vaccines to prevent HIV-1 transmission in China. Sera from a cohort of homosexual men, who have been managed by a major HIV clinical center in Beijing, China, were analyzed for cross-sectional neutralizing activities against pseudotyped viruses expressing Env antigens of the major subtype viruses (AE, BC and B subtypes) circulating in China. Neutralizing activities in infected patients' blood were most capable of neutralizing viruses in the homologous subtype; however, a subset of blood samples was able to achieve broad neutralizing activities across different subtypes. Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples. Our study confirmed the presence of broadly neutralizing sera in China's HIV-1 patient population. Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.

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Analysis of possible correlations between neutralization breadth in HIV-1 patient sera and selected known neutralizing epitopes V3 and CD4bs.A. Analysis on the relationship between the reduction of neutralizing activities after V3 peptide absorption in patient sera and the breadth of neutralization with the same patient sera. Percent reduction of neutralizing activities against pseudotyped SF162 was tested with individual patient serum (1∶20 dilution) after absorption with the subtype B consensus V3 peptide. The alignment of subtype B consensus (Cons-B) and SF162 V3 sequence is shown. The number of primary Env pseudotyped viruses (total 44) neutralized by each individual patient serum were calculated as shown in Fig. 1. Correlations and significance were determined using the Spearman method. B. The relationship between antibody titers to compete against neutralizing mAb b12 and the breadth of neutralization (number of viruses being neutralized) in the same patient sera was analyzed. Correlations and significance were determined using the Spearman method.
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pone-0047548-g004: Analysis of possible correlations between neutralization breadth in HIV-1 patient sera and selected known neutralizing epitopes V3 and CD4bs.A. Analysis on the relationship between the reduction of neutralizing activities after V3 peptide absorption in patient sera and the breadth of neutralization with the same patient sera. Percent reduction of neutralizing activities against pseudotyped SF162 was tested with individual patient serum (1∶20 dilution) after absorption with the subtype B consensus V3 peptide. The alignment of subtype B consensus (Cons-B) and SF162 V3 sequence is shown. The number of primary Env pseudotyped viruses (total 44) neutralized by each individual patient serum were calculated as shown in Fig. 1. Correlations and significance were determined using the Spearman method. B. The relationship between antibody titers to compete against neutralizing mAb b12 and the breadth of neutralization (number of viruses being neutralized) in the same patient sera was analyzed. Correlations and significance were determined using the Spearman method.

Mentions: In order to further understand the specificity of anti-Env antibody responses that may be responsible for the breadth of NAb against primary HIV-1 viruses in this cohort of HIV-1-infected patients, two types of assays were conducted. In the first assay, serum samples were treated with HIV-1 subtype B consensus V3 peptide before the same neutralization study was conducted against SF162, which can be neutralized by majority of the patient sera in this study. Decreases in NAb responses upon the treatment of this V3 peptide were observed although a significant number of sera only had a moderate drop (20–40%) with V3 peptide treatment (Fig. 4A). An overall inverse-correlation was observed between the reduction of neutralizing activity upon treatment with V3 peptide and the breadth of NAb responses (r = −0.409, p = 0.022). These results suggested that patient sera with broader neutralizing activities were less V3-dependent while those with narrower neutralizing activities were more V3-dependent against SF162 tested in this study.


Serum neutralizing activities from a Beijing homosexual male cohort infected with different subtypes of HIV-1 in China.

Zhang M, Jiao Y, Wang S, Zhang L, Huang Z, Chen Y, Wu H - PLoS ONE (2012)

Analysis of possible correlations between neutralization breadth in HIV-1 patient sera and selected known neutralizing epitopes V3 and CD4bs.A. Analysis on the relationship between the reduction of neutralizing activities after V3 peptide absorption in patient sera and the breadth of neutralization with the same patient sera. Percent reduction of neutralizing activities against pseudotyped SF162 was tested with individual patient serum (1∶20 dilution) after absorption with the subtype B consensus V3 peptide. The alignment of subtype B consensus (Cons-B) and SF162 V3 sequence is shown. The number of primary Env pseudotyped viruses (total 44) neutralized by each individual patient serum were calculated as shown in Fig. 1. Correlations and significance were determined using the Spearman method. B. The relationship between antibody titers to compete against neutralizing mAb b12 and the breadth of neutralization (number of viruses being neutralized) in the same patient sera was analyzed. Correlations and significance were determined using the Spearman method.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475692&req=5

pone-0047548-g004: Analysis of possible correlations between neutralization breadth in HIV-1 patient sera and selected known neutralizing epitopes V3 and CD4bs.A. Analysis on the relationship between the reduction of neutralizing activities after V3 peptide absorption in patient sera and the breadth of neutralization with the same patient sera. Percent reduction of neutralizing activities against pseudotyped SF162 was tested with individual patient serum (1∶20 dilution) after absorption with the subtype B consensus V3 peptide. The alignment of subtype B consensus (Cons-B) and SF162 V3 sequence is shown. The number of primary Env pseudotyped viruses (total 44) neutralized by each individual patient serum were calculated as shown in Fig. 1. Correlations and significance were determined using the Spearman method. B. The relationship between antibody titers to compete against neutralizing mAb b12 and the breadth of neutralization (number of viruses being neutralized) in the same patient sera was analyzed. Correlations and significance were determined using the Spearman method.
Mentions: In order to further understand the specificity of anti-Env antibody responses that may be responsible for the breadth of NAb against primary HIV-1 viruses in this cohort of HIV-1-infected patients, two types of assays were conducted. In the first assay, serum samples were treated with HIV-1 subtype B consensus V3 peptide before the same neutralization study was conducted against SF162, which can be neutralized by majority of the patient sera in this study. Decreases in NAb responses upon the treatment of this V3 peptide were observed although a significant number of sera only had a moderate drop (20–40%) with V3 peptide treatment (Fig. 4A). An overall inverse-correlation was observed between the reduction of neutralizing activity upon treatment with V3 peptide and the breadth of NAb responses (r = −0.409, p = 0.022). These results suggested that patient sera with broader neutralizing activities were less V3-dependent while those with narrower neutralizing activities were more V3-dependent against SF162 tested in this study.

Bottom Line: Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples.Our study confirmed the presence of broadly neutralizing sera in China's HIV-1 patient population.Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.

View Article: PubMed Central - PubMed

Affiliation: Jiangsu Province Key Laboratory in Infectious Diseases, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT
Protective antibodies play a critical role in an effective HIV vaccine; however, eliciting antibodies to block infection by viruses from diverse genetic subtypes remains a major challenge. As the world's most populous country, China has been under the threat of at least three major subtypes of circulating HIV-1 viruses. Understanding the cross reactivity and specificities of serum antibody responses that mediate broad neutralization of the virus in HIV-1 infected Chinese patients will provide valuable information for the design of vaccines to prevent HIV-1 transmission in China. Sera from a cohort of homosexual men, who have been managed by a major HIV clinical center in Beijing, China, were analyzed for cross-sectional neutralizing activities against pseudotyped viruses expressing Env antigens of the major subtype viruses (AE, BC and B subtypes) circulating in China. Neutralizing activities in infected patients' blood were most capable of neutralizing viruses in the homologous subtype; however, a subset of blood samples was able to achieve broad neutralizing activities across different subtypes. Such cross neutralizing activity took 1-2 years to develop and CD4 binding site antibodies were critical components in these blood samples. Our study confirmed the presence of broadly neutralizing sera in China's HIV-1 patient population. Understanding the specificity and breadth of these neutralizing activities can guide efforts for the development of HIV vaccines against major HIV-1 viruses in China.

Show MeSH
Related in: MedlinePlus