1. yet, the report of higher risk of transmission in the presence of 318 broad maternal plasma responses raises the question of whether bNAbs present in maternal 319 plasma select for neutralization-resistant viruses -which has important implications for passive 320 bNAb strategies in the setting of MTCT. We evaluated the neutralization sensitivity of the six 321 infant T/F viruses and their paired maternal non;Fouda;Several studies have established that infant T/F viruses are not uniformly neutralization-316 resistant to bNAbs compared to maternal non-transmitted viruses,2011
2. Infant T/F viruses and their 326 closest maternal non-transmitted viruses for mother-infant pairs 155.1 and 3902 were similarly 327 neutralization-sensitive to PG9 (Figure 6A). Moreover, for mother-infant pair 155.1, some of the 328 maternal variants were neutralization-sensitive to PG9, whereas other maternal variants and the 329 infant T/F virus were neutralization-resistant (Figure 6A). Interestingly, for mother-infant pair 330 0601, both the infant T/F virus and the closest maternal non-transmitted virus were 331 neutralization-resistant to PG9 whereas the more phylogenetically distant maternal non-332 transmitted viruses were uniformly neutralization-sensitive to PG9, suggesting the transmission 333 of a bNAb resistant virus (Figure 6A). Similarly, in assessing the sensitivity of paired mother and 334 infant viruses to V3 glycan-targeting bNAb PGT128, for mother-infant pair 9105, all of the 335 maternal non-transmitted viruses were uniformly neutralization-sensitive to PGT128 whereas the 336 infant T/F virus was neutralization;DH512, V2 glycan-targeting antibody PG9, and V3 glycan-targeting antibody PGT128
3. In observing the viral sequence 347 in this region, V2 glycan neutralization-resistant infant T/F virus 0616 and the closest 0601 348 maternal variant had large deletions within the V1V2 loop whereas the neutralization-sensitive 349 maternal non-transmitted variants did not have the V1V2 loop deletions (Figure S4), suggesting 350 that infant T/F viruses may acquire deletions that modulate neutralization-resistance to V2 351 glycan-targeting bNAbs. Similarly, infant T/F virus 9112 was neutralization-resistant to N332 400 and Malawian HIV-infected non-transmitting and transmitting women and tested their /infection (non-transmitted variants) and infant T/F viruses. Previous studies defined 403 that MTCT of HIV involves a genetic bottleneck where from a genetically diverse maternal virus 404 population, only one or a few viruses are transmitted (Braibant and Barin;Wolinsky;We next asked if infant T/F viruses 0616 and 9112 that appeared to be bNAb escape 340 variants were uniformly neutralization-resistant to additional V2 glycan-targeting and V3 glycan-341 targeting bNAbs, respectively. Consistent with the PG9 neutralization sensitivities, infant T/F 342 virus 0616 and the closest maternal variant were also neutralization-resistant to PG16 and 343 PGT125,1992