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Biology subjects

Ake, J. A.

Publications and source records attributed to Ake, J. A..

2 recordsLinked to original sources

Full-length next-generation sequencing of 11 HLA loci of more than 1000 individuals from clinical cohorts in East and West Africa

Human Leukocyte Antigen (HLA) loci have been implicated in several diseases from different world populations, including HIV-1. It is necessary to characterize HLA allele variation at the population level prior to investigating associations linked to human diseases. In global databases, limited high-resolution HLA allele types generated by next-generation sequencing (NGS) have been described for populations from African countries. We sought to expand our HLA NGS database to include a total of 1023 participants from multiple HIV clinical studies using full-length HLA genotyping by NGS. Collectively we describe HLA genotypes of individuals from Kenya (n=375), Uganda (n=338), Nigeria (n=139), Tanzania (n=89), and Mozambique (n=82). Overall, we identified 371 unique HLA alleles across 11 loci with the most frequent at each locus being A*02:01:01, B*53:01:01, C*04:01:01, C*06:02:01, DPA1*01:03:01, DPB1*01:01:01, DQA1*01:02:01, DQB1*06:02:01, DRB1*15:03:01, DRB3*02:02:01, DRB4*01:03:01, and DRB5*01:01:01. A total of 25 novel alleles were identified, including 4 with non-synonymous changes affecting the peptide binding groove of HLA molecules. This expansion of NGS based HLA data at the African population level will improve our understanding of human genetic variation and provide insights for vaccine development and targeted personalized therapies.

genetics↗

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

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.

microbiology↗