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by claude@2026-07, 2026-07-03
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This study compared neutralization sensitivity to three broadly neutralizing antibodies (bnAbs) among 25 clade C HIV-1 viruses isolated from breastmilk and 99 contemporaneous clade C viruses from adults with sexually acquired infection, using neutralization assays to generate IC80-based resistance patterns. The authors found that a higher proportion of breastmilk donor viruses showed resistance to multiple bnAbs than adult sexually transmitted viruses (43% of donors versus 8%; p=0.02), with breastmilk viruses being more resistant to PGT121 and VRC07.523 and showing a greater fraction resistant to VRC07.523 (94% vs. 43%; p=0.001). For viruses resistant to VRC07.523, the study reported an association with increased V3 glycosylation sites, and V3 glycan number was negatively correlated with VRC07.523 sensitivity (p=0.009 and p=0.007). The paper notes that vertically transmitted virus cohorts are often sparse and small and that more sequencing/screening of infant viruses is needed to better inform bnAb efficacy, emphasizing sampling limitations. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.
Abstract
HIV viruses that establish infection possess phenotypic and genotypic characteristics that have been selected for and that differ across transmission routes, including their susceptibility to broadly neutralizing antibodies (bnAbs). While sexually transmitted viruses have been well characterized, studies of vertically transmitted viruses are sparse and from cohorts that are often small in size and more than a decade old. To investigate whether viruses transmitted vertically during lactation possess distinct neutralization profiles compared to viruses transmitted sexually, we compared the neutralization sensitivity of 25 clade C breastmilk viruses to that of 99 contemporaneous clade C viruses from sera of adults with sexual acquisition against three bnAbs in clinical development.Three out of 7 breastmilk donors (43%) had one or more viruses resistant to 2 or more bnAbs, compared to 8 out of 99 (8%) contemporaneous adult viruses (p=0.02). Breastmilk viruses were more resistant to PGT121 and VRC07.523 (median IC80 >50 compared to 1.16 for PGT121, and 12.75 vs. 0.38 for VRC07.523; p=0.013 and <0.001 respectively), and more breastmilk viruses than adult viruses were resistant to VRC07.523 (94% vs. 43%, p=0.001). Interestingly, the breastmilk viruses most resistant to VRC07.523 had on average one or more glycans in V3 compared to adult transmitted viruses (median 3 vs. 2 glycosylation sites, including flanking position 295; p=0.009), and the number of V3 glycans was negatively correlated with VRC07.523 sensitivity (p=0.007). These findings highlight potential differences in bnAb susceptibility of vertically transmitted viruses and emphasize the need to increase sequencing efforts and screening of infant viruses to better inform the efficacy of candidate bnAbs to prevent vertical transmission of HIV.
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Abstract
HIV viruses that establish infection possess phenotypic and genotypic characteristics that have been selected for and that differ across transmission routes, including their susceptibility to broadly neutralizing antibodies (bnAbs). While sexually transmitted viruses have been well characterized, studies of vertically transmitted viruses are sparse and from cohorts that are often small in size and more than a decade old. To investigate whether viruses transmitted vertically during lactation possess distinct neutralization profiles compared to viruses transmitted sexually, we compared the neutralization sensitivity of 25 clade C breastmilk viruses to that of 99 contemporaneous clade C viruses from sera of adults with sexual acquisition against three bnAbs in clinical development.Three out of 7 breastmilk donors (43%) had one or more viruses resistant to 2 or more bnAbs, compared to 8 out of 99 (8%) contemporaneous adult viruses (p=0.02). Breastmilk viruses were more resistant to PGT121 and VRC07.523 (median IC80 >50 compared to 1.16 for PGT121, and 12.75 vs. 0.38 for VRC07.523; p=0.013 and <0.001 respectively), and more breastmilk viruses than adult viruses were resistant to VRC07.523 (94% vs. 43%, p=0.001). Interestingly, the breastmilk viruses most resistant to VRC07.523 had on average one or more glycans in V3 compared to adult transmitted viruses (median 3 vs. 2 glycosylation sites, including flanking position 295; p=0.009), and the number of V3 glycans was negatively correlated with VRC07.523 sensitivity (p=0.007). These findings highlight potential differences in bnAb susceptibility of vertically transmitted viruses and emphasize the need to increase sequencing efforts and screening of infant viruses to better inform the efficacy of candidate bnAbs to prevent vertical transmission of HIV.
Competing Interest Statement
The authors have declared no competing interest.
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