monoclonal antibodies
Pathogenesis and ImmunityA Novel Antigenic Site Spanning Domains I and III of the Zika Virus Envelope Glycoprotein Is the Target of Strongly Neutralizing Human Monoclonal AntibodiesPeople infected with Zika virus develop durable neutralizing antibodies that prevent repeat infections. In the current study, we characterize a ZIKV-neutralizing human monoclonal antibody isolated from a patient after recovery. Our studies establish a novel site on the viral envelope that is targeted by human neutralizing antibodies. Our results are relevant to understanding how antibodies block infection and to guiding the design and...
Virus-Cell InteractionsAntibody Screening System Using a Herpes Simplex Virus (HSV)-Based Probe To Identify a Novel Target for Receptor-Retargeted Oncolytic HSVsThe tropism of the cellular entry of HSV is dependent on the binding of the envelope gD to one of its authentic receptors. This can be fully retargeted to other receptors by inserting scFvs into gD with appropriate modifications.
Virus-Cell InteractionsUsing Split Luciferase Assay and Anti-Herpes Simplex Virus Glycoprotein Monoclonal Antibodies To Predict a Functional Binding Site between gD and gH/gLVirus entry and cell-cell fusion mediated by HSV require four essential glycoproteins, gD, gH/gL, gB, and a gD receptor. Virus-neutralizing antibodies directed against any of these proteins bind to residues within key functional sites and interfere with essential steps in the fusion pathway.
Vaccines and Antiviral Agents | SpotlightHigh-Resolution Mapping of Human Norovirus Antigens via Genomic Phage Display Library Selections and Deep SequencingNoV infections are a leading cause of gastroenteritis in the United States. Human NoVs exhibit extensive genetic and antigenic diversity, which makes it challenging to design a vaccine that provides broad protection against infection. Antibodies developed during the immune response play an important role in the control of NoV infections. Neutralizing antibodies that act by sterically blocking the site on the virus used to bind human...
Genetic Diversity and EvolutionComprehensive Assessment of the Antigenic Impact of Human Papillomavirus Lineage Variation on Recognition by Neutralizing Monoclonal Antibodies Raised against Lineage A Major Capsid Proteins of Vaccine-Related GenotypesHuman papillomavirus (HPV) is the causative agent of cervical and some other epithelial cancers. HPV vaccines generate functional (neutralizing) antibodies that target the virus particles (or capsids) of the most common HPV cancer-causing genotypes. Each genotype comprises variant forms that have arisen over millennia and which include changes within the capsid proteins. In this study, we explored the potential for these naturally...
Vaccines and Antiviral Agents | SpotlightCharacterization of Novel Cross-Reactive Influenza B Virus Hemagglutinin Head Specific Antibodies That Lack Hemagglutination Inhibition ActivityUnderstanding the immune response that older individuals mount to influenza virus vaccination and infection is critical in order to design better vaccines for this age group. Here, we show that older individuals make broadly neutralizing antibodies that have no hemagglutination-inhibiting activity and are less potent than strain-specific antibodies. These antibodies could drive viral escape from neutralization but did not result in...
Vaccines and Antiviral AgentsHuman Monoclonal Antibody Derived from Transchromosomic Cattle Neutralizes Multiple H1 Clades of Influenza A Virus by Recognizing a Novel Conformational Epitope in the Hemagglutinin Head DomainRespiratory diseases caused by influenza viruses still pose a serious concern to global health, and neutralizing antibodies constitute a promising area of antiviral therapeutics. However, the potential application of antibodies is often hampered by the challenge in generating nonimmunogenic antibodies in large scale. In the present study, transchromosomic (Tc) cattle were used for the generation of nonimmunogenic monoclonal antibodies (...
Pathogenesis and Immunity | SpotlightDiversity and Function of Maternal HIV-1-Specific Antibodies at the Time of Vertical TransmissionMother-to-child-transmission of HIV-1 offers a unique setting in which maternal antibodies both within the mother and passively transferred to the infant are present at the time of viral exposure. Untreated HIV-exposed human infants are infected at a rate of 30 to 40%, meaning that some infants do not get infected despite continued exposure to virus. Since the potential of HIV-specific immune responses to provide protection against HIV...
Vaccines and Antiviral AgentsAutologous Antibody Responses to an HIV Envelope Glycan Hole Are Not Easily Broadened in RabbitsA glycan hole is one of the most dominant autologous neutralizing epitopes targeted on BG505 and B41 SOSIP trimer-immunized rabbits. Our high-resolution cryo-electron microscopy (cryoEM) studies of B41 in complex with a B41-specific antibody complex elucidate the molecular basis of this strain-specific glycan hole response. We conclude that even for the immunodominant glycan hole shared between BG505 and B41, the prospect of designing...
