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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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Improvement of NAb responses after one year of HIV-1 infection.Panels A, B, C and D represent the percent (%) of neutralization at 1∶20 serum dilution against two sensitive subtype B viruses (SF162 and NL4-3), within 1 year, between 1–2 years, longer than 2 years of infection, or time of initial infection unknown. Panels E and F represent the percentage of HIV-1 infected patient sera that showed positive NAb responses (using IC50 at 1∶20 serum dilution as the cut-off) based on length of infection (<1 year, 1–2 years, and >2 years). Panel A shows neutralizing activities against two sensitive viruses (SF162 and NL4-3) and panel B against 44 pseudotyped viruses expressing primary Env antigens (see Fig. 1). The levels of statistical difference between patient sera with different lengths of infection are indicated, which were determined by Fisher exact test.
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pone-0047548-g003: Improvement of NAb responses after one year of HIV-1 infection.Panels A, B, C and D represent the percent (%) of neutralization at 1∶20 serum dilution against two sensitive subtype B viruses (SF162 and NL4-3), within 1 year, between 1–2 years, longer than 2 years of infection, or time of initial infection unknown. Panels E and F represent the percentage of HIV-1 infected patient sera that showed positive NAb responses (using IC50 at 1∶20 serum dilution as the cut-off) based on length of infection (<1 year, 1–2 years, and >2 years). Panel A shows neutralizing activities against two sensitive viruses (SF162 and NL4-3) and panel B against 44 pseudotyped viruses expressing primary Env antigens (see Fig. 1). The levels of statistical difference between patient sera with different lengths of infection are indicated, which were determined by Fisher exact test.

Mentions: Since many serum samples included in the current study did not show broad NAb responses until later in infection, it was interesting to examine whether a longer period of infection in the host may be needed in order to elicit broad NAb responses. Using subtype B virus-infected patient sera as an example, Fig. 3 (A–D) shows that NAb titers increased after one year’s infection against two sensitive viruses (SF162 and NL4-3); similar results were found using sera that showed positive neutralizing activities. When all serum samples were included, sera with positive neutralizing activities against the two sensitive viruses increased from less than 50% of the total samples for those with <1 year’s infection to close to 100% for those with >2 years’ infection (Fig. 3E). The same pattern was observed against 44 primary Env pseudotyped viruses (Fig. 3F), most of which were more resistant viruses. On average, less than 5% of the neutralizing events against the primary Env viruses were observed with sera from patients infected <1 year, but this rate increased to close to 20% with 1–2 years’ infection, and to more than 30% after two years’ infection (Fig. 3F).


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)

Improvement of NAb responses after one year of HIV-1 infection.Panels A, B, C and D represent the percent (%) of neutralization at 1∶20 serum dilution against two sensitive subtype B viruses (SF162 and NL4-3), within 1 year, between 1–2 years, longer than 2 years of infection, or time of initial infection unknown. Panels E and F represent the percentage of HIV-1 infected patient sera that showed positive NAb responses (using IC50 at 1∶20 serum dilution as the cut-off) based on length of infection (<1 year, 1–2 years, and >2 years). Panel A shows neutralizing activities against two sensitive viruses (SF162 and NL4-3) and panel B against 44 pseudotyped viruses expressing primary Env antigens (see Fig. 1). The levels of statistical difference between patient sera with different lengths of infection are indicated, which were determined by Fisher exact test.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0047548-g003: Improvement of NAb responses after one year of HIV-1 infection.Panels A, B, C and D represent the percent (%) of neutralization at 1∶20 serum dilution against two sensitive subtype B viruses (SF162 and NL4-3), within 1 year, between 1–2 years, longer than 2 years of infection, or time of initial infection unknown. Panels E and F represent the percentage of HIV-1 infected patient sera that showed positive NAb responses (using IC50 at 1∶20 serum dilution as the cut-off) based on length of infection (<1 year, 1–2 years, and >2 years). Panel A shows neutralizing activities against two sensitive viruses (SF162 and NL4-3) and panel B against 44 pseudotyped viruses expressing primary Env antigens (see Fig. 1). The levels of statistical difference between patient sera with different lengths of infection are indicated, which were determined by Fisher exact test.
Mentions: Since many serum samples included in the current study did not show broad NAb responses until later in infection, it was interesting to examine whether a longer period of infection in the host may be needed in order to elicit broad NAb responses. Using subtype B virus-infected patient sera as an example, Fig. 3 (A–D) shows that NAb titers increased after one year’s infection against two sensitive viruses (SF162 and NL4-3); similar results were found using sera that showed positive neutralizing activities. When all serum samples were included, sera with positive neutralizing activities against the two sensitive viruses increased from less than 50% of the total samples for those with <1 year’s infection to close to 100% for those with >2 years’ infection (Fig. 3E). The same pattern was observed against 44 primary Env pseudotyped viruses (Fig. 3F), most of which were more resistant viruses. On average, less than 5% of the neutralizing events against the primary Env viruses were observed with sera from patients infected <1 year, but this rate increased to close to 20% with 1–2 years’ infection, and to more than 30% after two years’ infection (Fig. 3F).

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