neutralization
Structure and AssemblyGlycoprotein C of Herpes Simplex Virus 1 Shields Glycoprotein B from Antibody NeutralizationHSV-1 causes lifelong infection in the human population and can be fatal in neonatal and immunocompromised individuals. There is no vaccine or cure, in part due to the ability of HSV to escape the host immune response by various mechanisms. The HSV particle contains at least 15 envelope proteins, four of which are required for entry and replication. This work suggests a novel role for gC in shielding the HSV entry glycoproteins. gC may...
Pathogenesis and ImmunityA New Family of Small-Molecule CD4-Mimetic Compounds Contacts Highly Conserved Aspartic Acid 368 of HIV-1 gp120 and Mediates Antibody-Dependent Cellular CytotoxicityHIV-1 has evolved multiple strategies to avoid humoral responses. One efficient mechanism is to keep its envelope glycoprotein (Env) in its “closed” conformation. Here, we report on a new family of small molecules that are able to “open up” Env, thus exposing vulnerable epitopes. This new family of molecules binds in the Phe43 cavity and contacts the highly conserved D368 residue. The structural and biological attributes of molecules of...
Vaccines and Antiviral AgentsA Replication-Defective Human Cytomegalovirus Vaccine Elicits Humoral Immune Responses Analogous to Those with Natural InfectionIn utero HCMV infection can lead to miscarriage or childhood disabilities, and an effective vaccine is urgently needed. Since children born to women who are seropositive prior to pregnancy are less likely to be affected by congenital HCMV infection, it has been hypothesized that a vaccine capable of inducing an immune response resembling the responses in HCMV-seropositive women may be effective. We previously described a...
Pathogenesis and ImmunityCD4 Incorporation into HIV-1 Viral Particles Exposes Envelope Epitopes Recognized by CD4-Induced AntibodiesIt has been well established that Env-CD4 complexes expose epitopes recognized by commonly elicited CD4-induced antibodies at the surface of HIV-1-infected cells, rendering them vulnerable to ADCC responses. Here, we show that CD4 incorporation has a profound impact on Env conformation at the surface of viral particles. Incorporated CD4 exposes CD4-induced epitopes on Env, rendering HIV-1 susceptible to neutralization by otherwise...
Vaccines and Antiviral AgentsXenoantigen-Dependent Complement-Mediated Neutralization of Lymphocytic Choriomeningitis Virus Glycoprotein-Pseudotyped Vesicular Stomatitis Virus in Human Serum...Systemic application aims to deliver oncolytic viruses to tumors as well as to metastatic lesions. However, we found that xenoantigens incorporated onto the viral surface from nonhuman production cell lines are recognized by natural antibodies in human serum and that the virus is thereby inactivated by complement lysis. Hence, to maximize the effective dose, careful selection of cell lines for virus production is crucial.
Vaccines and Antiviral AgentsAntigenicity and Immunogenicity of Differentially Glycosylated Hepatitis C Virus E2 Envelope Proteins Expressed in Mammalian and Insect CellsThe development of a vaccine for hepatitis C virus (HCV) remains a global health challenge. A major challenge for vaccine development is focusing the immune response on conserved regions of the HCV envelope protein, E2, capable of eliciting neutralizing antibodies. Modification of E2 by glycosylation might influence the immunogenicity of E2. Accordingly, we performed molecular and immunogenic comparisons of E2 produced in mammalian and...
Vaccines and Antiviral AgentsClosing and Opening Holes in the Glycan Shield of HIV-1 Envelope Glycoprotein SOSIP Trimers Can Redirect the Neutralizing Antibody Response to the Newly Unmasked EpitopesEngineered SOSIP trimers mimic envelope-glycoprotein spikes, which stud the surface of HIV-1 particles and mediate viral entry into cells. When used for immunizing test animals, they elicit antibodies that neutralize resistant sequence-matched HIV-1 isolates. These neutralizing antibodies recognize epitopes in holes in the glycan shield that covers the trimer. Here, we added glycans to block the most immunogenic neutralization epitopes...
Vaccines and Antiviral Agents | SpotlightElicitation of Protective Antibodies against 20 Years of Future H3N2 Cocirculating Influenza Virus Variants in Ferrets Preimmune to Historical H3N2 Influenza VirusesAfter exposure to influenza virus, the host generates neutralizing anti-hemagglutinin (anti-HA) antibodies against that specific infecting influenza strain. These antibodies can also neutralize some, but not all, cocirculating strains. The goal of next-generation influenza vaccines, such as HA head-based COBRA, is to stimulate broadly protective neutralizing antibodies against all strains circulating within a subtype, in particular...
Virus-Cell InteractionsMutations in the Spike Protein of Middle East Respiratory Syndrome Coronavirus Transmitted in Korea Increase Resistance to Antibody-Mediated NeutralizationMERS-CoV has pandemic potential, and it is important to identify mutations in viral proteins that might augment viral spread. In the course of a large hospital outbreak of MERS in the Republic of Korea in 2015, the spread of a viral variant that contained mutations in the viral spike protein was observed. These mutations were found to reduce receptor binding and viral infectivity. However, it remained unclear whether they also exerted...
Pathogenesis and ImmunityPotent Neutralizing Human Monoclonal Antibodies Preferentially Target Mature Dengue Virus Particles: Implication for Novel Strategy for Dengue VaccineWith an estimated 390 million infections per year, the four serotypes of dengue virus (DENV) cause the most important mosquito-borne viral disease in humans. The dengue vaccine Dengvaxia was licensed; however, its low efficacy among dengue-naive individuals and increased risk of causing severe dengue in children highlight the need for a better understanding of the role of human antibodies in immunity against DENV. DENV suspensions...