Barton F. Haynes
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View article: ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates
ALFQ adjuvanted HIV-1 envelope protein vaccination elicits durable functional antibody and cellular responses in nonhuman primates Open
Adjuvants play an important role in modulating antigen-specific immune responses. We conducted a comparative adjuvant immunogenicity study in Rhesus macaques using HIV-1 subtype B gp120 envelope protein, B.63521, formulated with aluminum h…
View article: Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity
Glycan-reactive antibodies isolated from human HIV-1 vaccine trial participants show broad pathogen cross-reactivity Open
HIV-1 continues to pose a significant global health challenge, requiring ongoing research into effective prevention and treatment strategies. Understanding the B-cell repertoire that can be engaged upon vaccination in humans is crucial for…
View article: Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies
Structural and genetic basis of HIV-1 envelope V2 apex recognition by rhesus broadly neutralizing antibodies Open
Broadly neutralizing antibodies targeting the V2 apex of HIV-1 envelope are desired as vaccine design templates, but few have been described. Here, we report 11 lineages of V2 apex–neutralizing antibodies from simian-human immunodeficiency…
View article: Design of SARS-CoV-2 RBD immunogens to focus immune responses toward conserved coronavirus epitopes
Design of SARS-CoV-2 RBD immunogens to focus immune responses toward conserved coronavirus epitopes Open
SARS-CoV-2 continues to evolve, with new variants emerging that evade pre-existing immunity and limit the efficacy of existing vaccines. One approach toward developing superior, variant-proof vaccines is to engineer immunogens that prefere…
View article: Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques
Transient glycan shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques Open
Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 CD4-binding site (CD4bs) occur infrequently in macaques and humans and have not been reproducibly elicited in any outbred animal model. To address this challenge, we first isolate…
View article: A neutralizing human antibody induces movement of the HCoV-229E receptor binding domain
A neutralizing human antibody induces movement of the HCoV-229E receptor binding domain Open
HCoV-229E is an endemic Alphacoronavirus that typically causes common cold-like disease in most healthy adults, but can also cause severe respiratory disease in the very young and the elderly. Although the virus was discovered over sixty y…
View article: Safety and implementation of phase I randomized GLA-SE–adjuvanted CH505TF gp120 HIV vaccine trial in newborns
Safety and implementation of phase I randomized GLA-SE–adjuvanted CH505TF gp120 HIV vaccine trial in newborns Open
BACKGROUNDThe neonatal immune system is uniquely poised to generate broadly neutralizing antibodies (bnAbs), and thus infants are ideal for evaluating HIV vaccine candidates. We present the design and safety of a new-in-infants glucopyrano…
View article: Disease diagnostics using machine learning of B cell and T cell receptor sequences
Disease diagnostics using machine learning of B cell and T cell receptor sequences Open
Clinical diagnosis typically incorporates physical examination, patient history, various laboratory tests, and imaging studies but makes limited use of the human immune system’s own record of antigen exposures encoded by receptors on B cel…
View article: Design of SARS-CoV-2 RBD Immunogens to Focus Immune Responses Towards Conserved Coronavirus Epitopes
Design of SARS-CoV-2 RBD Immunogens to Focus Immune Responses Towards Conserved Coronavirus Epitopes Open
SARS-CoV-2 continues to evolve, with new variants emerging that evade pre-existing immunity and limit the efficacy of existing vaccines. One approach towards developing superior, variant-proof vaccines is to engineer immunogens that prefer…
View article: Transient glycan-shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques
Transient glycan-shield reduction induces CD4-binding site broadly neutralizing antibodies in SHIV-infected macaques Open
SUMMARY Broadly neutralizing antibodies (bNAbs) targeting the HIV-1 CD4-binding site (CD4bs) occur infrequently in macaques and humans and have not been reproducibly elicited in any outbred animal model. To address this challenge, we first…
View article: Anti-HIV-1 B cell antigen receptor signaling and structure
Anti-HIV-1 B cell antigen receptor signaling and structure Open
The B cell antigen receptor (BCR) complex, comprised of antigen recognition and signaling components, functions in initiating B cell activation. While structural studies have described BCR domain organization, gaps remain in our understand…
View article: Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies
Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies Open
Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and in some cases, the same Ig-heavy chains. The current trial-and…
View article: Elimination of SHIV Infected Cells by Combinations of Bispecific HIVxCD3 DART® Molecules
Elimination of SHIV Infected Cells by Combinations of Bispecific HIVxCD3 DART® Molecules Open
Bispecific HIVxCD3 DART molecules that co-engage the viral envelope glycoprotein (Env) on HIV-1-infected cells and the CD3 receptor on CD3+ T cells are designed to mediate the cytolysis of HIV-1-infected, Env-expressing cells. Using a nove…
View article: HLA-E-VL9 antibodies enhance NK cell and CD8<sup>+</sup>T cell cytotoxicity against HIV-infected CD4<sup>+</sup>T cells
HLA-E-VL9 antibodies enhance NK cell and CD8<sup>+</sup>T cell cytotoxicity against HIV-infected CD4<sup>+</sup>T cells Open
SUMMARY A major natural killer (NK) cell and CD8 + T cell checkpoint is mediated by the inhibitory receptor NKG2A/CD94 and its ligand, HLA-E complexed with 9 amino acid HLA-Ia leader sequence-derived peptides termed VL9 (HLA-E-VL9). Here, …
View article: HIV-1 neutralizing antibodies in SHIV-infected macaques recapitulate structurally divergent modes of human V2 apex recognition with a single D gene
HIV-1 neutralizing antibodies in SHIV-infected macaques recapitulate structurally divergent modes of human V2 apex recognition with a single D gene Open
Broadly neutralizing antibodies targeting the V2 apex of the HIV-1 envelope trimer are among the most common specificities elicited in HIV-1-infected humans and simian-human immunodeficiency virus (SHIV)-infected macaques. To gain insight …
View article: An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals
An HIV-1 gp41 peptide-liposome vaccine elicits neutralizing epitope-targeted antibody responses in healthy individuals Open
Broadly neutralizing antibodies (bnAbs) that target the HIV gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand MPER bnAb precursors in mo…
View article: SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition
SARS-CoV-2 Omicron XBB lineage spike structures, conformations, antigenicity, and receptor recognition Open
A recombinant lineage of the SARS-CoV-2 Omicron variant, named XBB, appeared in late 2022 and evolved descendants that successively swept local and global populations. XBB lineage members were noted for their improved immune evasion and tr…
View article: Microsecond dynamics control the HIV-1 Envelope conformation
Microsecond dynamics control the HIV-1 Envelope conformation Open
The HIV-1 Envelope (Env) glycoprotein facilitates host cell fusion through a complex series of receptor-induced structural changes. Although remarkable progress has been made in understanding the structures of various Env conformations, mi…
View article: Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody
Discovery and Characterization of a Pan-betacoronavirus S2-binding antibody Open
SUMMARY/ABSTRACT Three coronaviruses have spilled over from animal reservoirs into the human population and caused deadly epidemics or pandemics. The continued emergence of coronaviruses highlights the need for pan-coronavirus intervention…
View article: Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates
Broadly neutralizing antibody induction by non-stabilized SARS-CoV-2 Spike mRNA vaccination in nonhuman primates Open
Immunization with mRNA or viral vectors encoding spike with diproline substitutions (S-2P) has provided protective immunity against severe COVID-19 disease. How immunization with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)…
View article: Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies
Engineering immunogens that select for specific mutations in HIV broadly neutralizing antibodies Open
Vaccine development targeting rapidly evolving pathogens such as HIV-1 requires induction of broadly neutralizing antibodies (bnAbs) with conserved paratopes and mutations, and, in some cases, the same Ig-heavy chains. The current trial-an…
View article: Engineered immunogens to elicit antibodies against conserved coronavirus epitopes
Engineered immunogens to elicit antibodies against conserved coronavirus epitopes Open
Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompas…
View article: The Duffy Antigen Receptor for Chemokines Null Promoter Variant Does Not Influence HIV-1 Acquisition or Disease Progression
The Duffy Antigen Receptor for Chemokines Null Promoter Variant Does Not Influence HIV-1 Acquisition or Disease Progression Open
Ma’am – We read with great interest the article by He et al. [2008] describing the effects on HIV acquisition and disease progression of a single-nucleotide polymorphism (SNP, rs2814778,-46T→C) that disrupts the promoter region of the Duff…
View article: Subordinate Effect of -21M HLA-B Dimorphism on NK Cell Repertoire Diversity and Function in HIV-1 Infected Individuals of African Origin
Subordinate Effect of -21M HLA-B Dimorphism on NK Cell Repertoire Diversity and Function in HIV-1 Infected Individuals of African Origin Open
Natural Killer (NK) cells play an important role in antiviral defense and their potent effector function identifies them as key candidates for immunotherapeutic interventions in chronic viral infections. Their remarkable functional agility…