immunization
Vaccines and Antiviral Agents | SpotlightTrivalent Glycoprotein Subunit Vaccine Prevents Neonatal Herpes Simplex Virus Mortality and MorbidityHerpes simplex virus is among the most serious infections of newborns. Current antiviral therapies can prevent mortality if infection is recognized early and treated promptly. Most children who survive nHSV develop lifelong neurological and behavioral deficits, despite aggressive antiviral treatment. We propose that maternal immunization could provide protection against HSV for both mother and baby. To this end, we used a trivalent...
Pathogenesis and ImmunityZika Virus Mucosal Infection Provides Protective ImmunityZika virus is a clinically significant human pathogen that is primarily transmitted and spread by Aedes species mosquitoes but is also sexually transmissible. The recent pandemic in the Americas led to an unprecedented increase of newborn babies with developmental brain and eye abnormalities. To date, there is no licensed vaccine or therapeutic intervention available for the fight against ZIKV. Understanding the sexual...
Pathogenesis and Immunity | SpotlightLoss of Resistance to Mousepox during Chronic Lymphocytic Choriomeningitis Virus Infection Is Associated with Impaired T-Cell Responses and Can Be Rescued by ImmunizationChronic viral infections may result in immunosuppression and enhanced susceptibility to infections with other pathogens. For example, we have recently shown that mice chronically infected with lymphocytic choriomeningitis virus (LCMV) clone 13 (CL13) are highly susceptible to mousepox, a disease that is caused by ectromelia virus and that is the mouse homolog of human smallpox. Here we show chronic CL13 infection severely disrupts the...
Vaccines and Antiviral AgentsBroadly Inhibiting Antineuraminidase Monoclonal Antibodies Induced by Trivalent Influenza Vaccine and H7N9 Infection in HumansAntibodies to the influenza virus NA can provide protection against influenza disease. Analysis of human antibodies to NA lags behind that of antibodies to HA. We show that human monoclonal antibodies against NA induced by vaccination and infection can be very broadly reactive, with the ability to inhibit a wide spectrum of N1 NAs on viruses isolated between 1918 and 2018. This suggests that antibodies to NA may be a useful therapy and...
Vaccines and Antiviral AgentsType I and Type III Interferons Differ in Their Adjuvant Activities for Influenza VaccinesInterferons can shape antiviral immune responses, but it is not well understood how they influence vaccine efficacy. We find that type I IFN preferentially promotes the production of antigen-specific IgG2c and IgA antibodies after infection with a live attenuated influenza virus or after immunization with influenza subunit vaccines. In contrast, type III IFN specifically enhances influenza virus-specific IgG1 and IgA production. The...
Pathogenesis and ImmunityAn Equine Herpesvirus Type 1 (EHV-1) Ab4 Open Reading Frame 2 Deletion Mutant Provides Immunity and Protection from EHV-1 Infection and DiseaseNasal equine herpesvirus type 1 (EHV-1) shedding is essential for virus transmission during outbreaks. Cell-associated viremia is a prerequisite for the most severe disease outcomes, abortion and equine herpesvirus myeloencephalopathy (EHM). Thus, protection from viremia is considered essential for preventing EHM. Ab4ΔORF2 vaccination prevented EHV-1 challenge virus replication in the upper respiratory tract in fully protected horses....
Vaccines and Antiviral AgentsComparative Evaluation of the Vaccine Efficacies of Three Adenovirus-Based Vector Types in the Friend Retrovirus Infection ModelAdV-based vectors are important tools for the development of vaccines against a wide range of pathogens. While AdV vectors are generally considered safe and highly effective, their application can be severely impaired by preexisting immunity due to the widespread seroprevalence of some AdV types. The characterization of different AdV types with regard to immunogenicity and efficacy in challenge models is of great importance for the...
Vaccines and Antiviral AgentsA Recombinant Rabies Virus Expressing the Marburg Virus Glycoprotein Is Dependent upon Antibody-Mediated Cellular Cytotoxicity for Protection against Marburg Virus Disease in a Murine ModelMarburg virus (MARV) is a virus similar to Ebola virus and also causes a hemorrhagic disease which is highly lethal. In contrast to EBOV, only a few vaccines have been developed against MARV, and researchers do not understand what kind of immune responses are required to protect from MARV. Here we show that antibodies directed against MARV after application of our vaccine protect in an animal system but fail to neutralize the virus in a...
Vaccines and Antiviral AgentsAntibody-Mediated Protective Mechanisms Induced by a Trivalent Parainfluenza Virus-Vectored Ebolavirus VaccineThe symptoms of the disease caused by the ebolaviruses Ebola, Bundibugyo, and Sudan are similar, and their areas of endemicity overlap. However, because of the limited antigenic relatedness of the ebolavirus glycoprotein (GP) used in all candidate vaccines against these viruses, they protect only against homologous and not against heterologous ebolaviruses. Therefore, a broadly specific pan-ebolavirus vaccine is required, and this might...
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...