A5076243363- Virus-based gene therapy research
- HIV Research and Treatment
- Viral Infections and Outbreaks Research
- vaccines and immunoinformatics approaches
- SARS-CoV-2 and COVID-19 Research
- Monoclonal and Polyclonal Antibodies Research
- Hepatitis B Virus Studies
- Immunotherapy and Immune Responses
- Virology and Viral Diseases
- Respiratory viral infections research
National Institutes of Health
2022-2024
National Institute of Allergy and Infectious Diseases
2022
Abstract Lassa virus (LASV) infection is expanding outside its traditionally endemic areas in West Africa, posing a pandemic biothreat. LASV-neutralizing antibodies, moreover, have proven difficult to elicit. To gain insight into LASV neutralization, here we develop prefusion-stabilized glycoprotein trimer (GPC), pan it against phage libraries comprising single-domain antibodies (nanobodies) from shark and camel, identify one, D5, which neutralizes LASV. Cryo-EM analyses reveal D5 recognize...
The HIV-1 fusion peptide has been identified as a site for elicitation of broadly neutralizing antibodies, with prior studies demonstrating that priming peptide-based immunogens and boosting soluble envelope (Env) trimers can elicit cross-clade HIV-1-neutralizing responses. To improve the breadth potency peptide-directed responses, we evaluated vaccine regimens incorporated diverse peptide-conjugates Env variation in length sequence.
The Pneumoviridae family of viruses includes human metapneumovirus (HMPV) and respiratory syncytial virus (RSV). closely related Paramyxoviridae parainfluenza (PIVs). These three viral pathogens cause acute tract infections with substantial disease burden in the young, elderly, immune-compromised. While promising subunit vaccines are being developed prefusion-stabilized forms fusion glycoproteins (Fs) RSV PIVs, for which neutralizing titers elicited by prefusion (pre-F) conformation F much...
ABSTRACT Lassa virus (LASV) is responsible for 100,000-300,000 zoonotic infections annually and poses a threat to public health. Development of antibody-based therapeutics or vaccines has been challenging because neutralizing antibodies – even among hemorrhagic fever survivors are generally low titer, the target antibodies, trimeric glycoprotein complex (GPC), type 1-fusion machine with GP1 GP2 subunits, difficult produce. Here, we use structure-based design obtain soluble LASV GPC by...
Conjugate-vaccine immunogens require three components: a carrier protein, an antigen, and crosslinker, capable of coupling antigen to while preserving both T-cell responses from protein B-cell antigen. We previously showed that the N-terminal eight residues HIV-1 fusion peptide (FP8) as could prime for broad cross-clade neutralizing responses, recombinant heavy chain tetanus toxin (rTTHC) provided optimal choice crosslinker impact antigenicity immunogenicity. Here, we delve more deeply into...