Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

Wieczorek, Lindsay; Sanders‐Buell, Eric; Zemil, Michelle; Molnar, Sebastian; Donofrio, G.; Townsley, Samantha; Chenine, Agnès Laurence; Bose, Meera; Trinh, Hung V.; Barrows, Brittani M; Sriplienchan, Somchai; Kitsiripornchai, Suchai; Nitayapan, Sorachai; Eller, Leigh-Anne; Rao, Mangala; Ferrari, Guido; Michael, Nelson L.; Ake, Julie A; Krebs, Shelly J.; Robb, Merlin L.; Tovanabutra, Sodsai; Polonis, Victoria R.

doi:10.1128/jvi.01635-22

Cited by 5 publications

(3 citation statements)

References 108 publications

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“…To determine whether this trend was applicable to other subtypes, we evaluated neutralization data from the LANL CATNAP database and our previous work [ 33 ], to characterize four additional subtypes ( Fig 5B–5E ). Due to the limits in data availability, not all NAbs are demonstrated and the fold change in Env sensitivity was determined over a two- or three-decade period, as indicated in each chart.…”

Section: Resultsmentioning

confidence: 99%

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Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States

Wieczorek,

Sanders-Buell,

Zemil

et al. 2023

PLoS Pathog

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Subtype B HIV-1 has been the primary driver of the HIV-1 epidemic in the United States (U.S.) for over forty years and is also a prominent subtype in the Americas, Europe, Australia, the Middle East and North Africa. In this study, the neutralization profiles of contemporary subtype B Envs from the U.S. were assessed to characterize changes in neutralization sensitivities over time. We generated a panel of 30 contemporary pseudoviruses (PSVs) and demonstrated continued diversification of subtype B Env from the 1980s up to 2018. Neutralization sensitivities of the contemporary subtype B PSVs were characterized using 31 neutralizing antibodies (NAbs) and were compared with strains from earlier in the HIV-1 pandemic. A significant reduction in Env neutralization sensitivity was observed for 27 out of 31 NAbs for the contemporary as compared to earlier-decade subtype B PSVs. A decline in neutralization sensitivity was observed across all Env domains; the NAbs that were most potent early in the pandemic suffered the greatest decline in potency over time. A meta-analysis demonstrated this trend across multiple subtypes. As HIV-1 Env diversification continues, changes in Env antigenicity and neutralization sensitivity should continue to be evaluated to inform the development of improved vaccine and antibody products to prevent and treat HIV-1.

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Section: Resultsmentioning

confidence: 99%

“…Neutralizing antibody titers were determined using TZM-bl cells [ 48 ] in a high-throughput assay utilizing robotic liquid handling, as previously described [ 33 ]. Plasma samples were prepared by heat inactivation at 56°C for 45 min, followed by 6 min centrifugation at 3000 rpm to remove particulates.…”

Section: Methodsmentioning

confidence: 99%

Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States

Wieczorek,

Sanders-Buell,

Zemil

et al. 2023

PLoS Pathog

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“…Since glycine and serine lack antibody-recognizable side chains, the redesigned loops are less likely to act as decoys attracting strain-specific antibody responses. A recent study found that long V1V2s in CRF01_AE Env were associated with the more rapid development of autologous neutralization in participants from the RV217 cohort 49 ; these results highlight the potential role of long HV loops in the development of strain specific responses – these strain-specific responses could be considered undesirable as autologous neutralization was not associated with the development of neutralization breadth in this cohort.…”

Section: Discussionmentioning

confidence: 75%

Contemporary HIV-1 consensus Env with redesigned hypervariable loops promote antibody binding

Bai,

Lewitus,

et al. 2023

Preprint

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An effective HIV-1 vaccine must elicit broadly neutralizing antibodies (bnAbs) against the highly diverse Envelope glycoproteins (Env) present globally. Since Env with the longest hypervariable (HV) loops were more resistant to the cognate bnAbs than Env with shorter HV loops, we redesigned hypervariable loops for updated HIV-1 Env consensus sequences of subtypes B and C and circulating recombinant form AE (CRF01_AE). We reduced the length of V1HV, V2H, and V5HV while maintaining the integrity of the Env structure and glycan shield, and we modified V4HV to account for its diverse structural context. Redesiged HV loops consisted mainly of glycine and serine to limit strain-specific targeting. Redesigned consensus Env of subtype B or CRF01_AE demonstrated increased magnitude of binding responses to pooled plasma samples and representative bnAbs. Together with other antigen optimization techniques, consensus Env with redesigned hypervariable loops can improve future HIV-1 vaccine antigens to elicit bnAbs.

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Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study

Marichannegowda,

Zemil,

Wieczorek

et al. 2023

eBioMedicine

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Evolution of Antibody Responses in HIV-1 CRF01_AE Acute Infection: Founder Envelope V1V2 Impacts the Timing and Magnitude of Autologous Neutralizing Antibodies

Cited by 5 publications

References 108 publications

Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States

Evolution of HIV-1 envelope towards reduced neutralization sensitivity, as demonstrated by contemporary HIV-1 subtype B from the United States

Contemporary HIV-1 consensus Env with redesigned hypervariable loops promote antibody binding

Tracking coreceptor switch of the transmitted/founder HIV-1 identifies co-evolution of HIV-1 antigenicity, coreceptor usage and CD4 subset targeting: the RV217 acute infection cohort study

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