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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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Related in: MedlinePlus

Mean change in B-P Scores in superinfected and singly infected study subjects.Circles and squares represent superinfected and singly infected samples, respectively. Horizontal lines indicate mean values. Red colour indicates the initial virus variants, whilst colour blue indicates the later virus variants.
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pone-0038989-g008: Mean change in B-P Scores in superinfected and singly infected study subjects.Circles and squares represent superinfected and singly infected samples, respectively. Horizontal lines indicate mean values. Red colour indicates the initial virus variants, whilst colour blue indicates the later virus variants.

Mentions: Breadth-Potency scores (B-P Scores) were calculated in order to be able to compare the neutralization capacity of the singly and superinfected patients’ plasma. The B-P score was computed by averaging all obtained x values, which were calculated by setting x = log10(IC50) for the available IC50s and by setting x = 0 for viruses that did not neutralize. This is equivalent to multiplying the fraction of viruses neutralized by the mean of the available IC50s, which in turn is the area under the B-P curve [40]. First, the neutralization breadth and potency of the respective first and last plasma samples against the initial pseudoviruses were analyzed. These pseudoviruses were called “initial virus variants” in the superinfected study group and “initial virus variants 1–4 or 5″ in the singly infected control subjects. For superinfected and singly-infected study subjects, these initial pseudoviruses were generated from plasma that was isolated an average of 0.25 months before the first plasma sample that was used for neutralizations and an average of 42.6 months before the last plasma sample used for neutralization. There was no significant difference between singly and superinfected study subjects in the time elapsed between plasma samples used for neutralization and the generation of pseudoviruses. The mean change of B-P Scores in the initial virus variants between the last and the first plasma sample tested was 1.112 in the superinfected study subjects (range from −0.110 to 1.784) and 1.280 in the singly infected subjects (range from −0.278 to 2.300). No significant difference in change of B-P Score was observed between singly and superinfected patients (p = 0.886) (Figure 8). Next, the neutralization breadth and potency of the respective first and last plasma samples against the “later” pseudoviruses were analyzed. These pseudoviruses were called “successive virus variants” in the superinfected study group and “initial virus variants 5–8 or 9″ in the singly infected control subjects. These later pseudoviruses were generated from plasma that was isolated an average of 13.125 months after the first plasma sample that was used for neutralizations and an average of 29.25 months before the last plasma sample that was used for neutralization. There was no significant difference between singly and superinfected study subjects in the time elapsed between plasma samples used for neutralization and the generation of pseudoviruses. The mean change of B-P Score between the last and the first plasma sample tested was 0.965 in the superinfected study subjects (range from 0.078 to 1.680) and 1.687 in the singly infected subjects (range from 1.097 to 2.113). No significant difference in change of B-P Score was observed between singly and superinfected patients (p = 0.2) (Figure 8).


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)

Mean change in B-P Scores in superinfected and singly infected study subjects.Circles and squares represent superinfected and singly infected samples, respectively. Horizontal lines indicate mean values. Red colour indicates the initial virus variants, whilst colour blue indicates the later virus variants.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038989-g008: Mean change in B-P Scores in superinfected and singly infected study subjects.Circles and squares represent superinfected and singly infected samples, respectively. Horizontal lines indicate mean values. Red colour indicates the initial virus variants, whilst colour blue indicates the later virus variants.
Mentions: Breadth-Potency scores (B-P Scores) were calculated in order to be able to compare the neutralization capacity of the singly and superinfected patients’ plasma. The B-P score was computed by averaging all obtained x values, which were calculated by setting x = log10(IC50) for the available IC50s and by setting x = 0 for viruses that did not neutralize. This is equivalent to multiplying the fraction of viruses neutralized by the mean of the available IC50s, which in turn is the area under the B-P curve [40]. First, the neutralization breadth and potency of the respective first and last plasma samples against the initial pseudoviruses were analyzed. These pseudoviruses were called “initial virus variants” in the superinfected study group and “initial virus variants 1–4 or 5″ in the singly infected control subjects. For superinfected and singly-infected study subjects, these initial pseudoviruses were generated from plasma that was isolated an average of 0.25 months before the first plasma sample that was used for neutralizations and an average of 42.6 months before the last plasma sample used for neutralization. There was no significant difference between singly and superinfected study subjects in the time elapsed between plasma samples used for neutralization and the generation of pseudoviruses. The mean change of B-P Scores in the initial virus variants between the last and the first plasma sample tested was 1.112 in the superinfected study subjects (range from −0.110 to 1.784) and 1.280 in the singly infected subjects (range from −0.278 to 2.300). No significant difference in change of B-P Score was observed between singly and superinfected patients (p = 0.886) (Figure 8). Next, the neutralization breadth and potency of the respective first and last plasma samples against the “later” pseudoviruses were analyzed. These pseudoviruses were called “successive virus variants” in the superinfected study group and “initial virus variants 5–8 or 9″ in the singly infected control subjects. These later pseudoviruses were generated from plasma that was isolated an average of 13.125 months after the first plasma sample that was used for neutralizations and an average of 29.25 months before the last plasma sample that was used for neutralization. There was no significant difference between singly and superinfected study subjects in the time elapsed between plasma samples used for neutralization and the generation of pseudoviruses. The mean change of B-P Score between the last and the first plasma sample tested was 0.965 in the superinfected study subjects (range from 0.078 to 1.680) and 1.687 in the singly infected subjects (range from 1.097 to 2.113). No significant difference in change of B-P Score was observed between singly and superinfected patients (p = 0.2) (Figure 8).

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