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Superinfection by discordant subtypes of HIV-1 does not enhance the neutralizing antibody response against autologous virus.

Mayr LM, Powell RL, Ngai JN, Takang WA, Nádas A, Nyambi PN - PLoS ONE (2012)

Bottom Line: Recent studies have demonstrated that both the potency and breadth of the humoral anti-HIV-1 immune response in generating neutralizing antibodies (nAbs) against heterologous viruses are significantly enhanced after superinfection by discordant HIV-1 subtypes, suggesting that repeated exposure of the immune system to highly diverse HIV-1 antigens can significantly improve anti-HIV-1 immunity.Analysis of the Breadth-Potency Scores confirmed that there was no significant difference in the increase in superinfected and singly infected study subjects (p = 0.234).These studies suggest that while superinfection by discordant subtypes induces antibodies with enhanced neutralizing breadth and potency against heterologous viruses, the potency to neutralize their autologous viruses is not better than those seen in singly infected patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, New York University School of Medicine, New York, New York, United States of America.

ABSTRACT
Recent studies have demonstrated that both the potency and breadth of the humoral anti-HIV-1 immune response in generating neutralizing antibodies (nAbs) against heterologous viruses are significantly enhanced after superinfection by discordant HIV-1 subtypes, suggesting that repeated exposure of the immune system to highly diverse HIV-1 antigens can significantly improve anti-HIV-1 immunity. Thus, we investigated whether sequential plasma from these subjects superinfected with discordant HIV-1 subtypes, who exhibit broad nAbs against heterologous viruses, also neutralize their discordant early autologous viruses with increasing potency. Comparing the neutralization capacities of sequential plasma obtained before and after superinfection of 4 subjects to those of matched plasma obtained from 4 singly infected control subjects, no difference in the increase in neutralization capacity was observed between the two groups (p = 0.328). Overall, a higher increase in neutralization over time was detected in the singly infected patients (mean change in IC(50) titer from first to last plasma sample: 183.4) compared to the superinfected study subjects (mean change in IC(50) titer from first to last plasma sample: 66.5). Analysis of the Breadth-Potency Scores confirmed that there was no significant difference in the increase in superinfected and singly infected study subjects (p = 0.234). These studies suggest that while superinfection by discordant subtypes induces antibodies with enhanced neutralizing breadth and potency against heterologous viruses, the potency to neutralize their autologous viruses is not better than those seen in singly infected patients.

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Neutralization of autologous virus variants by serially-diluted plasma obtained from study subject CMNYU107.A: Mean IC50 values with standard deviation of initial and superinfecting virus variants. B: Titration of last plasma against initial (mean of initial variants in red) and successive virus variants (mean of successive variants in blue). Only variants that reached 50% neutralization are included.
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pone-0038989-g002: Neutralization of autologous virus variants by serially-diluted plasma obtained from study subject CMNYU107.A: Mean IC50 values with standard deviation of initial and superinfecting virus variants. B: Titration of last plasma against initial (mean of initial variants in red) and successive virus variants (mean of successive variants in blue). Only variants that reached 50% neutralization are included.

Mentions: In our neutralization studies, the plasma sample obtained before superinfection (referred to as first plasma) did not achieve 50% neutralization of the initial or the superinfecting autologous virus variants (Figure 2A). However, the plasma sample obtained 15 months after superinfection (referred to as last plasma) was able to achieve 50% neutralization of 5 of the 6 initial variants (variants 2–6) (mean IC50 titer 38) as well as 5 of the 6 superinfecting virus variants with IC50 titers ranging from 33 to 59 (mean IC50 titer 39) (Figures 2A and 2B). This increase in neutralization by the plasma sample obtained 15 months after superinfection was statistically significant for both initial and superinfecting variants (p = 0.0043).


Superinfection by discordant subtypes of HIV-1 does not enhance the neutralizing antibody response against autologous virus.

Mayr LM, Powell RL, Ngai JN, Takang WA, Nádas A, Nyambi PN - PLoS ONE (2012)

Neutralization of autologous virus variants by serially-diluted plasma obtained from study subject CMNYU107.A: Mean IC50 values with standard deviation of initial and superinfecting virus variants. B: Titration of last plasma against initial (mean of initial variants in red) and successive virus variants (mean of successive variants in blue). Only variants that reached 50% neutralization are included.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3375243&req=5

pone-0038989-g002: Neutralization of autologous virus variants by serially-diluted plasma obtained from study subject CMNYU107.A: Mean IC50 values with standard deviation of initial and superinfecting virus variants. B: Titration of last plasma against initial (mean of initial variants in red) and successive virus variants (mean of successive variants in blue). Only variants that reached 50% neutralization are included.
Mentions: In our neutralization studies, the plasma sample obtained before superinfection (referred to as first plasma) did not achieve 50% neutralization of the initial or the superinfecting autologous virus variants (Figure 2A). However, the plasma sample obtained 15 months after superinfection (referred to as last plasma) was able to achieve 50% neutralization of 5 of the 6 initial variants (variants 2–6) (mean IC50 titer 38) as well as 5 of the 6 superinfecting virus variants with IC50 titers ranging from 33 to 59 (mean IC50 titer 39) (Figures 2A and 2B). This increase in neutralization by the plasma sample obtained 15 months after superinfection was statistically significant for both initial and superinfecting variants (p = 0.0043).

Bottom Line: Recent studies have demonstrated that both the potency and breadth of the humoral anti-HIV-1 immune response in generating neutralizing antibodies (nAbs) against heterologous viruses are significantly enhanced after superinfection by discordant HIV-1 subtypes, suggesting that repeated exposure of the immune system to highly diverse HIV-1 antigens can significantly improve anti-HIV-1 immunity.Analysis of the Breadth-Potency Scores confirmed that there was no significant difference in the increase in superinfected and singly infected study subjects (p = 0.234).These studies suggest that while superinfection by discordant subtypes induces antibodies with enhanced neutralizing breadth and potency against heterologous viruses, the potency to neutralize their autologous viruses is not better than those seen in singly infected patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Pathology, New York University School of Medicine, New York, New York, United States of America.

ABSTRACT
Recent studies have demonstrated that both the potency and breadth of the humoral anti-HIV-1 immune response in generating neutralizing antibodies (nAbs) against heterologous viruses are significantly enhanced after superinfection by discordant HIV-1 subtypes, suggesting that repeated exposure of the immune system to highly diverse HIV-1 antigens can significantly improve anti-HIV-1 immunity. Thus, we investigated whether sequential plasma from these subjects superinfected with discordant HIV-1 subtypes, who exhibit broad nAbs against heterologous viruses, also neutralize their discordant early autologous viruses with increasing potency. Comparing the neutralization capacities of sequential plasma obtained before and after superinfection of 4 subjects to those of matched plasma obtained from 4 singly infected control subjects, no difference in the increase in neutralization capacity was observed between the two groups (p = 0.328). Overall, a higher increase in neutralization over time was detected in the singly infected patients (mean change in IC(50) titer from first to last plasma sample: 183.4) compared to the superinfected study subjects (mean change in IC(50) titer from first to last plasma sample: 66.5). Analysis of the Breadth-Potency Scores confirmed that there was no significant difference in the increase in superinfected and singly infected study subjects (p = 0.234). These studies suggest that while superinfection by discordant subtypes induces antibodies with enhanced neutralizing breadth and potency against heterologous viruses, the potency to neutralize their autologous viruses is not better than those seen in singly infected patients.

Show MeSH
Related in: MedlinePlus