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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

Neutralization of autologous PBMC derived virus by serially-diluted plasma.Mean IC50 values with standard deviation of A: study subject CMNYU107 (superinfected). B: study subject CMNYU179 (singly infected).
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pone-0038989-g007: Neutralization of autologous PBMC derived virus by serially-diluted plasma.Mean IC50 values with standard deviation of A: study subject CMNYU107 (superinfected). B: study subject CMNYU179 (singly infected).

Mentions: The pseudoviruses used in our neutralization studies described above bear the gp120 portion of the envelope derived from the study subjects’ plasma. Therefore the gp120-gp41 envelopes are chimeras that may not display the same epitopes as the native envelope would in its natural form. Anti-gp41 antibodies may be present in the patient plasma that might not recognize the gp41 used for the pseudoviruses. We therefore questioned whether the gp120 pseudotyped viruses used in our studies would similarly be neutralized like the viruses isolated from patient PBMCs. For this, we isolated the early autologous viruses from two patients (CMNYU107 [superinfected] and CMNYU179 [singly infected]), using the same time points that were used for pseudovirus construction, and compared their neutralization sensitivity with those of the corresponding pseudotyped viruses. In study subject CMNYU107, just as the first plasma sample (obtained 12 months before superinfection) did not neutralize the pseudoviruses, it also did not neutralize the PBMC derived viruses. Furthermore, the last plasma sample acquired 15 months after superinfection) similarly neutralized both the initial and superinfecting pseudovirus variants as well as the PBMC derived initial and superinfecting viruses (Figures 2 and 7A). In patient CMNYU179 the first plasma sample did not neutralize the PBMC derived viruses but neutralized 3 of 9 pseudovirus variants at low level. The last plasma sample of study subject CMNYU179 was able to neutralize all pseudovirus variants and the PBMC derived viruses (Figures 6B and 7B). From this we conclude that the envelopes in the pseudoviruses studied are representative of the gp160 envelopes in the natural viruses.


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 PBMC derived virus by serially-diluted plasma.Mean IC50 values with standard deviation of A: study subject CMNYU107 (superinfected). B: study subject CMNYU179 (singly infected).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0038989-g007: Neutralization of autologous PBMC derived virus by serially-diluted plasma.Mean IC50 values with standard deviation of A: study subject CMNYU107 (superinfected). B: study subject CMNYU179 (singly infected).
Mentions: The pseudoviruses used in our neutralization studies described above bear the gp120 portion of the envelope derived from the study subjects’ plasma. Therefore the gp120-gp41 envelopes are chimeras that may not display the same epitopes as the native envelope would in its natural form. Anti-gp41 antibodies may be present in the patient plasma that might not recognize the gp41 used for the pseudoviruses. We therefore questioned whether the gp120 pseudotyped viruses used in our studies would similarly be neutralized like the viruses isolated from patient PBMCs. For this, we isolated the early autologous viruses from two patients (CMNYU107 [superinfected] and CMNYU179 [singly infected]), using the same time points that were used for pseudovirus construction, and compared their neutralization sensitivity with those of the corresponding pseudotyped viruses. In study subject CMNYU107, just as the first plasma sample (obtained 12 months before superinfection) did not neutralize the pseudoviruses, it also did not neutralize the PBMC derived viruses. Furthermore, the last plasma sample acquired 15 months after superinfection) similarly neutralized both the initial and superinfecting pseudovirus variants as well as the PBMC derived initial and superinfecting viruses (Figures 2 and 7A). In patient CMNYU179 the first plasma sample did not neutralize the PBMC derived viruses but neutralized 3 of 9 pseudovirus variants at low level. The last plasma sample of study subject CMNYU179 was able to neutralize all pseudovirus variants and the PBMC derived viruses (Figures 6B and 7B). From this we conclude that the envelopes in the pseudoviruses studied are representative of the gp160 envelopes in the natural viruses.

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