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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.

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Comparison of GMTs between intra-subtype and subtype B/subtype A/CRF01_AE/inter- subtype virus strain set.The difference of GMTs between CRF-matched (CRF07_BC) and subtype C, subtype B, subtype A, CRF01_AE, inter-subtype specific (excluding all the CRF07_BC and subtype C viruses) virus sets is illustrated in the overall sample (a) and BCN sample population (b), respectively. While the difference of GMTs between intra-subtype (CRF07_BC and subtype C) and subtype B, subtype A, CRF01_AE, inter-subtype specific (excluding all the CRF07_BC and subtype C viruses) virus sets is exhibited in the overall sample (c) and BCN sample population (d), respectively. The number in the bracket following the particular subtype on the x-axis indicates the numbers of viruses used for comparison. 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 the six groups is indicated: *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001; ****P < 0.0001 (Mann-Whitney U test).
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f1: Comparison of GMTs between intra-subtype and subtype B/subtype A/CRF01_AE/inter- subtype virus strain set.The difference of GMTs between CRF-matched (CRF07_BC) and subtype C, subtype B, subtype A, CRF01_AE, inter-subtype specific (excluding all the CRF07_BC and subtype C viruses) virus sets is illustrated in the overall sample (a) and BCN sample population (b), respectively. While the difference of GMTs between intra-subtype (CRF07_BC and subtype C) and subtype B, subtype A, CRF01_AE, inter-subtype specific (excluding all the CRF07_BC and subtype C viruses) virus sets is exhibited in the overall sample (c) and BCN sample population (d), respectively. The number in the bracket following the particular subtype on the x-axis indicates the numbers of viruses used for comparison. 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 the six groups is indicated: *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001; ****P < 0.0001 (Mann-Whitney U test).

Mentions: The NAb magnitude between subtype-matched CRF07_BC viruses and non-subtype-matched viruses, including subtype B, subtype A, CRF01_AE, and inter-subtype (excluding all the CRF07_BC and subtype C viruses as a whole), significantly differed (Fig. 1a, p < 0.0001 for all pairs). GMTs between subtype C and CRF07_BC viruses were comparable, which is in agreement with CRF07_BC envelope being derived from subtype C and its epidemiology history1618. Within the BCN group, a significant difference in GMTs between subtype-matched CRF07_BC viruses and non-subtype-matched viruses was observed (Fig. 1b, p < 0.0001 for all pairs except for subtype C, p = 0.0435). Even the magnitude between subtype C viruses and non-subtype-matched viruses including subtype B, subtype A, CRF01_AE, and inter-subtype also significantly differed in both overall (Fig. 1a, p < 0.001 for all pairs) and BCN (Fig. 1b, p < 0.01 for all pairs) groups.


Profiling the neutralizing antibody response in chronically HIV-1 CRF07_BC-infected intravenous drug users na ï ve to antiretroviral therapy
Comparison of GMTs between intra-subtype and subtype B/subtype A/CRF01_AE/inter- subtype virus strain set.The difference of GMTs between CRF-matched (CRF07_BC) and subtype C, subtype B, subtype A, CRF01_AE, inter-subtype specific (excluding all the CRF07_BC and subtype C viruses) virus sets is illustrated in the overall sample (a) and BCN sample population (b), respectively. While the difference of GMTs between intra-subtype (CRF07_BC and subtype C) and subtype B, subtype A, CRF01_AE, inter-subtype specific (excluding all the CRF07_BC and subtype C viruses) virus sets is exhibited in the overall sample (c) and BCN sample population (d), respectively. The number in the bracket following the particular subtype on the x-axis indicates the numbers of viruses used for comparison. 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 the six groups is indicated: *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001; ****P < 0.0001 (Mann-Whitney U test).
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f1: Comparison of GMTs between intra-subtype and subtype B/subtype A/CRF01_AE/inter- subtype virus strain set.The difference of GMTs between CRF-matched (CRF07_BC) and subtype C, subtype B, subtype A, CRF01_AE, inter-subtype specific (excluding all the CRF07_BC and subtype C viruses) virus sets is illustrated in the overall sample (a) and BCN sample population (b), respectively. While the difference of GMTs between intra-subtype (CRF07_BC and subtype C) and subtype B, subtype A, CRF01_AE, inter-subtype specific (excluding all the CRF07_BC and subtype C viruses) virus sets is exhibited in the overall sample (c) and BCN sample population (d), respectively. The number in the bracket following the particular subtype on the x-axis indicates the numbers of viruses used for comparison. 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 the six groups is indicated: *0.01 < P < 0.05; **0.001 < P < 0.01; ***P < 0.001; ****P < 0.0001 (Mann-Whitney U test).
Mentions: The NAb magnitude between subtype-matched CRF07_BC viruses and non-subtype-matched viruses, including subtype B, subtype A, CRF01_AE, and inter-subtype (excluding all the CRF07_BC and subtype C viruses as a whole), significantly differed (Fig. 1a, p < 0.0001 for all pairs). GMTs between subtype C and CRF07_BC viruses were comparable, which is in agreement with CRF07_BC envelope being derived from subtype C and its epidemiology history1618. Within the BCN group, a significant difference in GMTs between subtype-matched CRF07_BC viruses and non-subtype-matched viruses was observed (Fig. 1b, p < 0.0001 for all pairs except for subtype C, p = 0.0435). Even the magnitude between subtype C viruses and non-subtype-matched viruses including subtype B, subtype A, CRF01_AE, and inter-subtype also significantly differed in both overall (Fig. 1a, p < 0.001 for all pairs) and BCN (Fig. 1b, p < 0.01 for all pairs) groups.

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