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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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NAb activities against HIV-1 pseudotyped viruses.Neutralization was shown as the percent inhibition of virus infection at 1∶20 dilution of the patient sera or using 10 µg/ml of monoclonal antibodies (b12, 2G12, and 4E10). “−“ indicates that percent of neutralization was below 50%. Percent of neutralization between 50–75% or greater than 75% are highlighted in yellow or red, respectively. The HIV-1 pseudotyped viruses used for neutralization assays are shown in the second row from top from “NL4-3” to “CM235.c11” with subtype indicated above the virus panel. “MuLV” is the murine leukemia virus used as negative control for neutralization assays. “NJ0XX”s in the far left column indicates individual patient serum samples; patient HIV subtypes are indicated above each group of samples. Known neutralizing monoclonal antibodies, IgG1 b12, 2G12 and 4E10, served as positive controls for neutralization assays.
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pone-0047548-g001: NAb activities against HIV-1 pseudotyped viruses.Neutralization was shown as the percent inhibition of virus infection at 1∶20 dilution of the patient sera or using 10 µg/ml of monoclonal antibodies (b12, 2G12, and 4E10). “−“ indicates that percent of neutralization was below 50%. Percent of neutralization between 50–75% or greater than 75% are highlighted in yellow or red, respectively. The HIV-1 pseudotyped viruses used for neutralization assays are shown in the second row from top from “NL4-3” to “CM235.c11” with subtype indicated above the virus panel. “MuLV” is the murine leukemia virus used as negative control for neutralization assays. “NJ0XX”s in the far left column indicates individual patient serum samples; patient HIV subtypes are indicated above each group of samples. Known neutralizing monoclonal antibodies, IgG1 b12, 2G12 and 4E10, served as positive controls for neutralization assays.

Mentions: NAb analysis was conducted against pseudotyped virus infection in TZM-bl cells (Fig. 1). A panel of pseudotyped viruses expressing 44 primary HIV-1 Env antigens was included in this study: 14 from subtype B viruses, 11 from subtype BC, 7 from subtype C, and 12 from subtype AE. Two pseudotyped viruses expressing either an Env antigen from a T-cell line adapted (TCLA) virus (NL4-3) or an Env from a sensitive primary virus (SF162) were included as controls. The breadth and potency of such activities varied widely among this cohort. Given the large differences in NAb titers, a summary of neutralizing activities was compiled by using the same serum dilution at 1∶20. The percent inhibition at this serum dilution was reported to indicate the relative strength of such activities when inhibition less than 50% was considered negative in the current assay (Fig. 1).


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)

NAb activities against HIV-1 pseudotyped viruses.Neutralization was shown as the percent inhibition of virus infection at 1∶20 dilution of the patient sera or using 10 µg/ml of monoclonal antibodies (b12, 2G12, and 4E10). “−“ indicates that percent of neutralization was below 50%. Percent of neutralization between 50–75% or greater than 75% are highlighted in yellow or red, respectively. The HIV-1 pseudotyped viruses used for neutralization assays are shown in the second row from top from “NL4-3” to “CM235.c11” with subtype indicated above the virus panel. “MuLV” is the murine leukemia virus used as negative control for neutralization assays. “NJ0XX”s in the far left column indicates individual patient serum samples; patient HIV subtypes are indicated above each group of samples. Known neutralizing monoclonal antibodies, IgG1 b12, 2G12 and 4E10, served as positive controls for neutralization assays.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0047548-g001: NAb activities against HIV-1 pseudotyped viruses.Neutralization was shown as the percent inhibition of virus infection at 1∶20 dilution of the patient sera or using 10 µg/ml of monoclonal antibodies (b12, 2G12, and 4E10). “−“ indicates that percent of neutralization was below 50%. Percent of neutralization between 50–75% or greater than 75% are highlighted in yellow or red, respectively. The HIV-1 pseudotyped viruses used for neutralization assays are shown in the second row from top from “NL4-3” to “CM235.c11” with subtype indicated above the virus panel. “MuLV” is the murine leukemia virus used as negative control for neutralization assays. “NJ0XX”s in the far left column indicates individual patient serum samples; patient HIV subtypes are indicated above each group of samples. Known neutralizing monoclonal antibodies, IgG1 b12, 2G12 and 4E10, served as positive controls for neutralization assays.
Mentions: NAb analysis was conducted against pseudotyped virus infection in TZM-bl cells (Fig. 1). A panel of pseudotyped viruses expressing 44 primary HIV-1 Env antigens was included in this study: 14 from subtype B viruses, 11 from subtype BC, 7 from subtype C, and 12 from subtype AE. Two pseudotyped viruses expressing either an Env antigen from a T-cell line adapted (TCLA) virus (NL4-3) or an Env from a sensitive primary virus (SF162) were included as controls. The breadth and potency of such activities varied widely among this cohort. Given the large differences in NAb titers, a summary of neutralizing activities was compiled by using the same serum dilution at 1∶20. The percent inhibition at this serum dilution was reported to indicate the relative strength of such activities when inhibition less than 50% was considered negative in the current assay (Fig. 1).

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