Alison Burns
- Viral gastroenteritis research and epidemiology
- SARS-CoV-2 and COVID-19 Research
- HIV Research and Treatment
- COVID-19 Clinical Research Studies
- HIV/AIDS drug development and treatment
- T-cell and B-cell Immunology
- Bacteriophages and microbial interactions
- Virology and Viral Diseases
- Bacillus and Francisella bacterial research
- vaccines and immunoinformatics approaches
- Cytomegalovirus and herpesvirus research
- Monoclonal and Polyclonal Antibodies Research
- Animal Virus Infections Studies
- Immune Cell Function and Interaction
- Respiratory viral infections research
- Virus-based gene therapy research
Scripps Research Institute
2020-2024
International AIDS Vaccine Initiative
2020-2024
Countermeasures to prevent and treat coronavirus disease 2019 (COVID-19) are a global health priority. We enrolled cohort of severe acute respiratory syndrome 2 (SARS-CoV-2)-recovered participants, developed neutralization assays investigate antibody responses, adapted our high-throughput generation pipeline rapidly screen more than 1800 antibodies, established an animal model test protection. isolated potent neutralizing antibodies (nAbs) two epitopes on the receptor binding domain (RBD)...
Germline-targeting immunogens hold promise for initiating the induction of broadly neutralizing antibodies (bnAbs) to HIV and other pathogens. However, antibody-antigen recognition is typically dominated by heavy chain complementarity determining region 3 (HCDR3) interactions, vaccine priming HCDR3-dominant bnAbs germline-targeting has not been demonstrated in humans or outbred animals. In this work, immunization with N332-GT5, an envelope trimer designed target precursors bnAb BG18, primed...
ABSTRACT The development of countermeasures to prevent and treat COVID-19 is a global health priority. In under 7 weeks, we enrolled cohort SARS-CoV-2-recovered participants, developed neutralization assays interrogate serum monoclonal antibody responses, adapted our high throughput isolation, production characterization pipeline rapidly screen over 1000 antigen-specific antibodies, established an animal model test protection. We report multiple highly potent neutralizing antibodies (nAbs)...
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need for strategies to rapidly develop neutralizing monoclonal antibodies that can function as prophylactic and therapeutic agents help guide vaccine design. Here, we demonstrate engineering approaches be used refocus an existing antibody neutralizes one virus but not a related virus. Through rapid affinity maturation strategy, engineered CR3022, SARS-CoV-1–neutralizing antibody, bind receptor...
BG505 SOSIP is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of sequential immunogen regimen to induce broadly neutralizing antibodies (bnAbs). Rhesus macaques are considered the most appropriate pre-clinical animal model for monitoring antibody (Ab) responses. Accordingly, we report here isolation 45 autologous (nAbs) with multiple specificities from SOSIP-immunized and SHIV-infected rhesus macaques. We associate potent neutralization two...
Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This is exacerbated by emergence spread SARS-CoV-2 variants concern (VOCs) that shown some resistance to vaccine responses. Here we report isolation five neutralizing mAbs from Indian convalescent donor, out two (THSC20.HVTR04 THSC20.HVTR26) showed potent neutralization VOCs at...
Abstract SIVmac239 infection of macaques is a favored model human HIV infection. However, the envelope (Env) trimer structure, glycan occupancy, and targets ability neutralizing antibodies (nAbs) to protect against remain unknown. Here, we report isolation nAbs that recognize hole V1/V4 loop. A high-resolution structure Env trimer-nAb complex shows many similarities SIVcpz Envs, but with distinct V4 features an extended V1 Moreover, has higher shield density than may contribute poor or...
Vaccination strategies aimed at maturing broadly neutralizing antibodies (bnAbs) from naïve precursors are hindered by unusual features that characterize these Abs, including insertions and deletions (indels). Longitudinal studies of natural HIV infection cases shed light on the complex processes underlying bnAb development have suggested a role for superinfection as potential enhancer neutralization breadth. Here we describe potent lineage was elicited two founder viruses to inform vaccine...
ABSTRACT The emergence of SARS-CoV-2 underscores the need for strategies to rapidly develop neutralizing monoclonal antibodies that can function as prophylactic and therapeutic agents help guide vaccine design. Here, we demonstrate engineering approaches be used refocus an existing antibody a related but resistant virus. Using rapid affinity maturation strategy, engineered CR3022, SARS-CoV-1 antibody, bind receptor binding domain with >1000-fold improved affinity. CR3022 neutralized...
BG505 SOSIP.664 is a well-characterized near-native recombinant HIV Envelope (Env) trimer that holds promise as part of sequential immunogen regime for an vaccine. has been tested in many preclinical animal models and now first-in-human phase I clinical trials. Rhesus macaques are considered the most similar terms nAb responses to humans. Accordingly, we report here isolation 45 nAbs with multiple specificities from immunized infected rhesus macaques.Notably, all autologous bind close...
ABSTRACT The rapid spread of SARS-CoV-2 variants poses a constant threat escape from monoclonal antibody and vaccine countermeasures. Mutations in the ACE2 receptor binding site on surface S protein have been shown to disrupt prevent viral neutralization. Here, we use directed evolution-based approach engineer three neutralizing antibodies for enhanced protein. engineered showed increased vitro functional activity terms neutralization potency and/or breadth against variants. Deep mutational...
Although efficacious vaccines have significantly reduced the morbidity and mortality due to COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This is exacerbated by emergence spread of SARS-CoV-2 variants concern (VOCs) that shown some resistance vaccine responses. Here we report isolation two highly potently neutralizing mAbs (THSC20.HVTR04 THSC20.HVTR26) from Indian convalescent donor, neutralize VOCs at picomolar...
SUMMARY SIVmac239 infection of macaques is a favored model human HIV infection. However, the envelope (Env) trimer structure, glycan occupancy, and targets ability neutralizing antibodies (nAbs) to protect against remain unknown. Here, we report isolation nAbs that recognize hole V1/V4 loop. A high-resolution structure Env trimer-nAb complex shows many similarities SIVcpz Envs, but with distinct V4 features an extended V1 Moreover, has higher shield density than may contribute poor or...