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. 2013;8(1):e53920.
doi: 10.1371/journal.pone.0053920. Epub 2013 Jan 7.

CRF01_AE-specific neutralizing activity observed in plasma derived from HIV-1-infected Thai patients residing in northern Thailand: comparison of neutralizing breadth and potency between plasma derived from rapid and slow progressors

Affiliations

CRF01_AE-specific neutralizing activity observed in plasma derived from HIV-1-infected Thai patients residing in northern Thailand: comparison of neutralizing breadth and potency between plasma derived from rapid and slow progressors

Sompong Sapsutthipas et al. PLoS One. 2013.

Abstract

Background: Development of a protective vaccine against human immunodeficiency virus type 1 (HIV-1) is an important subject in the field of medical sciences; however, it has not yet been achieved. Potent and broadly neutralizing antibodies are found in the plasma of some HIV-1-infected patients, whereas such antibody responses have failed to be induced by currently used vaccine antigens. In order to develop effective vaccine antigens, it is important to reveal the molecular mechanism of how strong humoral immune responses are induced in infected patients. As part of such studies, we examined the correlation between the anti-HIV-1 neutralizing antibody response and disease progression.

Methodology/principal findings: We evaluated the anti-HIV-1 neutralizing activity of plasma derived from 33 rapid and 34 slow progressors residing in northern Thailand. The level of neutralizing activity varied considerably among plasmas, and no statistically significant differences in the potency and breadth of neutralizing activities were observed overall between plasma derived from rapid and slow progressors; however, plasma of 4 slow progressors showed neutralizing activity against all target viruses, whereas none of the plasma of rapid progressors showed such neutralizing activity. In addition, 21% and 9% of plasmas derived from slow and rapid progressors inhibited the replication of more than 80% of CRF01_AE Env-recombinant viruses tested, respectively. Neutralization of subtype B and C Env-recombinant viruses by the selected plasma was also examined; however, these plasma samples inhibited the replication of only a few viruses tested.

Conclusions/significance: Although no statistically significant differences were observed in the potency and breadth of anti-HIV-1 neutralizing activities between plasma derived from rapid and slow progressors, several plasma samples derived from slow progressors neutralized CRF01_AE Env-recombinant viruses more frequently than those from rapid progressors. In addition, plasma derived from HIV-1-infected Thai patients showed CRF01_AE-specific neutralizing activity.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Anti-HIV-1 neutralizing activity of plasma derived from 33 rapid progressors against AE-Env-recombinant viruses.
Neutralizing activity of plasma samples against 8 AE-Env-recombinant viruses was evaluated and reciprocal plasma dilution at which viral replication was suppressed by 50% (50% inhibitory dilution, ID50) was calculated, as described in Methods. Data are presented as the means of at least three independent experiments. Plasma IDs and AE-Env-recombinant viruses tested are denoted on the left side and above the panel, respectively. In addition, mean ID50 values and the percentages of virus/plasma combinations (% neutralization) in which viral neutralization was observed among the data sets in horizontal and vertical directions are shown on the right side and bottom of the panel, respectively. ID50 values >500, values 100–500, and values 20–100 are highlighted in red, orange and yellow, respectively. In addition, no neutralization (ID50 values <20) of a recombinant virus is denoted by a gray background.
Figure 2
Figure 2. Anti-HIV-1 neutralizing activity of plasma derived from 34 slow progressors against AE-Env-recombinant viruses.
Neutralizing activity of plasma samples against 8 AE-Env-recombinant viruses was evaluated as described in the legend to Figure 1. Data are presented as the means of at least three independent experiments. Plasma IDs and AE-Env-recombinant viruses tested are denoted on the left side and above the panel, respectively. In addition, mean ID50 values and the percentages of virus/plasma combinations (% neutralization) in which viral neutralization was observed among the data sets in horizontal and vertical directions are shown on the right side and bottom of the panel, respectively. ID50 values >500, values 100–500 and values 20–100 are highlighted in red, orange and yellow, respectively. No neutralization (ID50 values <20) of a recombinant virus is denoted by a gray background. Plasma samples that neutralized all recombinant viruses tested are highlighted in green.
Figure 3
Figure 3. Comparison of the neutralization breadth between plasma derived from rapid and slow progressors.
The proportion of AE-Env-recombinant viruses in which replication was inhibited by a plasma sample was calculated and plotted. The levels of plasma-mediated neutralization against 60% and 80% of recombinant viruses tested are highlighted by horizontal blue and red grid lines, respectively. Plasma IDs are denoted below the panels.
Figure 4
Figure 4. Anti-HIV-1 neutralizing activity of 6 selected plasma samples against B-Env- and C-Env-recombinant viruses.
Neutralizing activity of 6 plasma samples against 5 B-Env- and 6 C-Env-recombinant viruses was evaluated as described in the legend to Figure 1. Data are presented as the means of at least three independent experiments. Plasma IDs and Env-recombinant viruses tested are denoted on the left side and above the panel, respectively. ID50 values 100–500 and 20–100 are highlighted in orange and yellow, respectively. No neutralization (ID50 values <20) of a recombinant virus is denoted by a gray background.

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This work was supported by the program of the Japan Initiative for Global Research Network on Infectious Diseases (J-GRID) by the Ministry of Education, Culture, Sports, Science and Technology of Japan, and the research budget of the Department of Medical Sciences, Ministry of Public Health of Thailand. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.