Regulation of humoral immunity to a virus-like particle vaccine candidate

类病毒颗粒疫苗候选物的体液免疫调节

• 批准号: 9387500
• 负责人: Madelyn Ruth Schmidt
• 金额: $ 25.13万
• 依托单位: UNIV OF MASSACHUSETTS MED SCH WORCESTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-16 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9387500
• 关键词: Adaptive Immune System; Address; Adjuvant; Adoptive Transfer; Affinity; Agonist; Antibody Affinity; Antibody Formation; Antibody Response; Antigens; B-Cell Activation; B-Lymphocytes; Bone Marrow; Cell surface; Cells; Cessation of life; Characteristics; Cotton Rats; Cytoplasmic Tail; Data; Dendritic Cells; Development; Elderly; Event; Future; G-substrate; GTP-Binding Proteins; Generations; Glycoproteins; Goals; Helper-Inducer T-Lymphocyte; Hospitalization; Human; Humoral Immunities; Immune; Immune response; Immune system; Immunity; Immunization; Immunize; Immunocompromised Host; In Vitro; Individual; Infant; Infection; Infectious Agent; Innate Immune System; Knockout Mice; Link; Lower Respiratory Tract Infection; Lung diseases; Membrane Proteins; Memory B-Lymphocyte; Mus; Mutant Strains Mice; Newcastle disease virus; Nucleoproteins; Plasma Cells; Plasmablast; Population; Preparation; Primary Cell Cultures; Production; Receptor Signaling; Regulation; Respiratory Failure; Respiratory Syncytial Virus Infections; Respiratory syncytial virus; Series; Signal Induction; Signal Pathway; Signal Transduction; Structure of germinal center of lymph node; Surface; System; T-Lymphocyte; Testing; Up-Regulation; Vaccines; Viral Proteins; Virus; Virus Replication; Virus-like particle; cytokine; design; experimental study; glycoprotein G; immune activation; in vivo; macrophage; mutant mouse model; neutralizing antibody; novel; novel vaccines; pathogen; receptor; research clinical testing; response; vaccine candidate

Project Summary and Relevance Human respiratory syncytial virus (RSV) is a major cause of serious lower respiratory tract infections and hospitalization in infants, the elderly and immunocompromised individuals. Natural infection does not induce durable protective immunity to the virus and multiple reinfections can occur even within the same year. To date, there is as yet no effective vaccine or treatment. We have developed novel RSV-virus-like particle (VLP) vaccine candidates composed of Newcastle Disease Virus nucleoprotein and membrane proteins that express RSV F and G glycoproteins ectodomains fused with NDV glycoprotein cytoplasmic domains. This VLP induces long-lived protective neutralizing antibody responses and memory B cells in mice when given once in the absence of adjuvant. Mice challenged with RSV post immunization clear the virus and do not display enhanced pulmonary disease. Because adjuvant is not required for this protective immune response, we propose that the VLP directly stimulates the innate immune system, such as TLRs or MAV. We will investigate this possibility by using mutant mouse models deficient in single components of the innate immune system and the impact on development of durable protective immunity. These studies will provide essential information for the future development of our vaccine candidate and define the most efficacious TLR agonists for clinical testing

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