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Broadly neutralizing, MN-like PND-directed antibodies in Rwandan children with long-term HIV1 infection
C Fraisier1, P Van de Perre, P Lepage
1INSERM U271, Lyon, France.
Insights
Antibodies targeting the HIV-1 V3 domain are linked to prolonged survival in children with perinatally acquired HIV-1 infection. This suggests V3-specific immune responses may be crucial for better outcomes in pediatric HIV-1.
Area of Science:
- Immunology
- Virology
- Pediatric Infectious Diseases
Background:
- Perinatally HIV-1 infected children exhibit variable disease progression.
- Long-term non-progressors (long survivors) offer insights into protective immune mechanisms against HIV-1.
Purpose of the Study:
- To investigate the neutralizing antibody responses in Rwandan children with prolonged survival from perinatally acquired HIV-1 infection.
- To compare humoral immunity in long-surviving children with those who developed AIDS.
Main Methods:
- Sera from 11 long-surviving (LS) and 16 AIDS children were tested for neutralizing antibodies against HIV-1 strains (HIV-1MN, HIV-1RII, HIV-1LAI).
- In vitro assays assessed neutralization of cell-free infection and inhibition of syncytium formation.
- Reactivity and avidity to HIV-1 V3 peptides (HIV-1MN, US/European, African consensus) were analyzed.
Main Results:
- Sera from LS children showed significantly higher neutralizing activity against HIV-1MN and HIV-1LAI compared to AIDS children.
- LS children's sera demonstrated enhanced inhibition of syncytium formation induced by HIV-1MN.
- Higher reactivity and IgG avidity to V3 peptides, particularly the African consensus peptide, were observed in LS children.
Conclusions:
- Humoral response to the HIV-1 V3 domain, associated with broad neutralization, may contribute to prolonged survival in perinatally infected children.
- The observed specificity against HIV-1MN suggests a potential prevalence of MN-related strains in Rwanda.
- An MN-related principal neutralizing domain sequence could be a key target for vaccine development in this region.
Abstract:
Sera from 11 perinatally HIV1-infected Rwandan children with prolonged survival were tested in vitro for the presence of neutralizing antibodies against different HIV1 strains. These 11 sera from long survivor (LS) children were compared with 16 sera from Rwandan children with AIDS. Sera from HIV1-infected children exhibited the greatest neutralizing activity against HIV1MN cell-free infection. They also inhibited HIV1RII and HIV1LAI cell-free infection with lower titres. Higher neutralization titres were observed in sera from LS compared to the AIDS group, with a significant difference for HIV1MN and HIV1LAI strains. Sera from LS children also inhibited syncytium formation induced by HIV1MN-infected cells with higher titres than AIDS children. Sera from the HIV1-infected children showed reactivity to the HIV1MN V3 peptide, as well as to both the US/European and the African consensus V3 peptides. Higher reactivity was observed in sera from LS than from AIDS children, and the difference was significant toward the African consensus peptide. The LS children also had significantly higher V3MN IgG avidity than the AIDS children. These data support the notion that the humoral response to the V3 domain, associated with a broadly neutralizing activity, may be an important factor in the prolonged survival of these children. The specificity against HIV1MN also suggests that an antigenically MN-related strain may be prevalent in Rwanda, and that an MN-related principal neutralizing domain sequence could be an important determinant for candidate vaccines in this part of Africa.