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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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Related in: MedlinePlus

MPER peptide inhibition of neutralizing activities of Env-specific mAbs and HIV-1 patient sera.A: MPER inhibition of NAb activities of mAbs (b12 against CD4bs, 2F5 and 4E10 against MPER) as control; B: MPER inhibition of NAb activities of patient sera with relative broad NAb activities (NJ009, NJ010, NJ012, NJ019, NJ025, NJ028, NJ030, NJ034, and NJ040).
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pone-0047548-g005: MPER peptide inhibition of neutralizing activities of Env-specific mAbs and HIV-1 patient sera.A: MPER inhibition of NAb activities of mAbs (b12 against CD4bs, 2F5 and 4E10 against MPER) as control; B: MPER inhibition of NAb activities of patient sera with relative broad NAb activities (NJ009, NJ010, NJ012, NJ019, NJ025, NJ028, NJ030, NJ034, and NJ040).

Mentions: Nine serum samples with relative broad NAb activities were further treated with HIV-1 Group M consensus MPER peptides (six peptide pool spanning both 2F5 and 4E10 epitopes) before the same neutralization study was conducted against SF162. Decreases in NAb activities upon treatment of MPER peptides were only observed in patient NJ040 and not in the other eight sera samples (NJ009, NJ010, NJ012, NJ019, NJ025, NJ025, NJ028, NJ030, and NJ034) (Fig. 5B). To control the MPER absorption assays, CD4bs-specific mAb b12 and MPER-specific mAbs 2F5 and 4E10 were also treated with MPER peptides before neutralization. As expected, MPER peptides could inhibit the NAb activities of MPER-specific mAbs 2F5 and 4E10 but could not inhibit the NAb activity of gp120-specific mAb b12 (Fig. 5A). These results suggest that patient sera with broader neutralizing activities are not MPER-dependent.


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)

MPER peptide inhibition of neutralizing activities of Env-specific mAbs and HIV-1 patient sera.A: MPER inhibition of NAb activities of mAbs (b12 against CD4bs, 2F5 and 4E10 against MPER) as control; B: MPER inhibition of NAb activities of patient sera with relative broad NAb activities (NJ009, NJ010, NJ012, NJ019, NJ025, NJ028, NJ030, NJ034, and NJ040).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0047548-g005: MPER peptide inhibition of neutralizing activities of Env-specific mAbs and HIV-1 patient sera.A: MPER inhibition of NAb activities of mAbs (b12 against CD4bs, 2F5 and 4E10 against MPER) as control; B: MPER inhibition of NAb activities of patient sera with relative broad NAb activities (NJ009, NJ010, NJ012, NJ019, NJ025, NJ028, NJ030, NJ034, and NJ040).
Mentions: Nine serum samples with relative broad NAb activities were further treated with HIV-1 Group M consensus MPER peptides (six peptide pool spanning both 2F5 and 4E10 epitopes) before the same neutralization study was conducted against SF162. Decreases in NAb activities upon treatment of MPER peptides were only observed in patient NJ040 and not in the other eight sera samples (NJ009, NJ010, NJ012, NJ019, NJ025, NJ025, NJ028, NJ030, and NJ034) (Fig. 5B). To control the MPER absorption assays, CD4bs-specific mAb b12 and MPER-specific mAbs 2F5 and 4E10 were also treated with MPER peptides before neutralization. As expected, MPER peptides could inhibit the NAb activities of MPER-specific mAbs 2F5 and 4E10 but could not inhibit the NAb activity of gp120-specific mAb b12 (Fig. 5A). These results suggest that patient sera with broader neutralizing activities are not MPER-dependent.

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