Limits...
Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users na ï ve to antiretroviral therapy

View Article: PubMed Central - PubMed

ABSTRACT

Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a large, multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses. Furthermore, we compared the neutralization pattern of CRF07_BC-infected people with that of subtype B’-infected individuals in China. Of the 98 plasma samples tested, 18% neutralized more than 80% of viruses in the panel, and 53% neutralized more than 50%, suggesting the presence of broadly NAbs in these individuals. A preferential intra-subtype neutralization of CRF07_BC was found. Notably, CRF07_BC-infected individuals generated higher neutralization titers against intra-subtype viruses than subtype B’-infected individuals with longer infection length. However, subtype B’-infected individuals mounted broader neutralization responses against inter-subtype viruses than CRF07_BC infection with shorter infection time, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to IgG fraction, and half of them developed CD4 binding site antibody reactivity. Heatmap analysis identified three statistically robust clusters of plasmas that offer valuable resources for further in-depth virological and immunological study.

No MeSH data available.


Related in: MedlinePlus

Comparison of NAb potency against the intra-subtype virus (a), CRF01_AE virus (b) and subtype A virus (c) between FPD and IDU cohort.The difference of GMTs of intra-subtype (a), CRF01_AE (b) and subtype A (c) virus set between IDU and FPD cohort is displayed for the different sample population. P-values (two-tailed) are based on the Mann-Whitney U test. The error bars show the median with the interquartile range. The significant difference between each group is indicated: *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001; ****P < 0.0001 (Mann-Whitney U test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5384219&req=5

f2: Comparison of NAb potency against the intra-subtype virus (a), CRF01_AE virus (b) and subtype A virus (c) between FPD and IDU cohort.The difference of GMTs of intra-subtype (a), CRF01_AE (b) and subtype A (c) virus set between IDU and FPD cohort is displayed for the different sample population. P-values (two-tailed) are based on the Mann-Whitney U test. The error bars show the median with the interquartile range. The significant difference between each group is indicated: *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001; ****P < 0.0001 (Mann-Whitney U test).

Mentions: To determine which portion of NAb magnitude contributed to these differences, we compared neutralization magnitude among each sample groups from both cohorts against intra-subtype viruses (Fig. 2a, the subtype B viruses used for FPD), and non-subtype-matched CRF01_AE (Fig. 2b) and subtype A (Fig. 2c) viruses. Since no subtype-matched (subtype B’) viruses were used for FPD cohort, it’s reasonable to combine the subtype-matched CRF07_BC and subtype C viruses as the intra-subtype virus set (n = 15) for IDU cohort to avoid the overestimate by only using CRF07_BC viruses closely genetically related to the strains circulating in IDU cohort. We observed significant differences between GMTs against intra-subtype viruses among all sample groups, including overall samples, BCN samples, M-BCN samples, and Non-BCN samples (Fig. 2a, p < 0.0001 for all pairs). All sample groups had higher GMTs in the IDU cohort than in the FPD cohort against their intra-subtype viruses (Fig. 2a, median GMTs: 78.31 versus 40.45 in the overall group; 272.31 versus 94.61 in the BCN group; 107.46 versus 50.45 in the M-BCN group; and 37.97 versus 16.34 in the Non-BCN group). Even the intra-subtype virus set for IDU cohort was restricted to the subtype C (n = 5) virus only, the significant statistic difference of NAb magnitude between both cohorts against the intra-subtype virus was still found (p ≤ 0.0186 for all pairs) among all samples group.


Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users na ï ve to antiretroviral therapy
Comparison of NAb potency against the intra-subtype virus (a), CRF01_AE virus (b) and subtype A virus (c) between FPD and IDU cohort.The difference of GMTs of intra-subtype (a), CRF01_AE (b) and subtype A (c) virus set between IDU and FPD cohort is displayed for the different sample population. P-values (two-tailed) are based on the Mann-Whitney U test. The error bars show the median with the interquartile range. The significant difference between each group is indicated: *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001; ****P < 0.0001 (Mann-Whitney U test).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5384219&req=5

f2: Comparison of NAb potency against the intra-subtype virus (a), CRF01_AE virus (b) and subtype A virus (c) between FPD and IDU cohort.The difference of GMTs of intra-subtype (a), CRF01_AE (b) and subtype A (c) virus set between IDU and FPD cohort is displayed for the different sample population. P-values (two-tailed) are based on the Mann-Whitney U test. The error bars show the median with the interquartile range. The significant difference between each group is indicated: *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001; ****P < 0.0001 (Mann-Whitney U test).
Mentions: To determine which portion of NAb magnitude contributed to these differences, we compared neutralization magnitude among each sample groups from both cohorts against intra-subtype viruses (Fig. 2a, the subtype B viruses used for FPD), and non-subtype-matched CRF01_AE (Fig. 2b) and subtype A (Fig. 2c) viruses. Since no subtype-matched (subtype B’) viruses were used for FPD cohort, it’s reasonable to combine the subtype-matched CRF07_BC and subtype C viruses as the intra-subtype virus set (n = 15) for IDU cohort to avoid the overestimate by only using CRF07_BC viruses closely genetically related to the strains circulating in IDU cohort. We observed significant differences between GMTs against intra-subtype viruses among all sample groups, including overall samples, BCN samples, M-BCN samples, and Non-BCN samples (Fig. 2a, p < 0.0001 for all pairs). All sample groups had higher GMTs in the IDU cohort than in the FPD cohort against their intra-subtype viruses (Fig. 2a, median GMTs: 78.31 versus 40.45 in the overall group; 272.31 versus 94.61 in the BCN group; 107.46 versus 50.45 in the M-BCN group; and 37.97 versus 16.34 in the Non-BCN group). Even the intra-subtype virus set for IDU cohort was restricted to the subtype C (n = 5) virus only, the significant statistic difference of NAb magnitude between both cohorts against the intra-subtype virus was still found (p ≤ 0.0186 for all pairs) among all samples group.

View Article: PubMed Central - PubMed

ABSTRACT

Characterizing neutralizing antibody (NAb) responses in individuals infected with diverse HIV-1 strains is necessary to reveal the novel targets for regional preventive and therapeutic strategies development. We evaluated the prevalence, breadth, and potency of NAb responses in 98 CRF07_BC-infected individuals using a large, multi-subtype panel of 30 tier 2-3 Env-pseudotyped viruses. Furthermore, we compared the neutralization pattern of CRF07_BC-infected people with that of subtype B&rsquo;-infected individuals in China. Of the 98 plasma samples tested, 18% neutralized more than 80% of viruses in the panel, and 53% neutralized more than 50%, suggesting the presence of broadly NAbs in these individuals. A preferential intra-subtype neutralization of CRF07_BC was found. Notably, CRF07_BC-infected individuals generated higher neutralization titers against intra-subtype viruses than subtype B&rsquo;-infected individuals with longer infection length. However, subtype B&rsquo;-infected individuals mounted broader neutralization responses against inter-subtype viruses than CRF07_BC infection with shorter infection time, indicating the transition from narrow autologous to broad heterologous neutralization over time. Neutralization activity of the top six plasmas from each cohort was attributable to IgG fraction, and half of them developed CD4 binding site antibody reactivity. Heatmap analysis identified three statistically robust clusters of plasmas that offer valuable resources for further in-depth virological and immunological study.

No MeSH data available.


Related in: MedlinePlus