Journal Article

Safety and immunogenicity of NYVAC-JEV and ALVAC-JEV attenuated recombinant Japanese encephalitis virus — poxvirus vaccines in vaccinia-nonimmune and vaccinia-immune humans

Shope, Robert E., Konishi, Eiji, Kurane, Ichiro, Tang, Douglas B., Vaughn, David W., Mason, Peter W., Smucny, John J., Hoke, Charles H., Marks, Donald H., Kanesa-thasan, Niranjan

2000

Overview

A controlled, randomized, double-blind clinical trial evaluated whether two attenuated recombinant poxviruses with identical Japanese encephalitis virus (JEV) gene insertions, NYVAC-JEV and ALVAC-JEV, were safe and immunogenic in volunteers. Groups of 10 volunteers distinguished by vaccinia immune status received two doses of each vaccine. The vaccines appeared to be equally safe and well tolerated in volunteers, but more reactogenic than licensed formalin-inactivated JE and placebo vaccines given as controls. NYVAC-JEV and ALVAC-JEV vaccine recipients had frequent occurrence of local warmth, erythema, tenderness, and/or arm pain after vaccination. There was no apparent effect of vaccinia immune status on frequency or magnitude of local and systemic reactions. NYVAC-JEV elicited antibody responses to JEV antigens in recipients but ALVAC-JEV vaccine poorly induced antibody responses. However, NYVAC-JEV vaccine induced neutralizing antibody responses only in vaccinia-nonimmune recipients while vaccinia-immune volunteers failed to develop protective antibodies (5/5 vs. 0/5 seroconversion, p<0.01). These data suggest that preexisting immunity to poxvirus vector may suppress antibody responses to recombinant gene products.

• Publisher: Elsevier Ltd,Elsevier BV,Elsevier
• Subject: Antibodies, Viral / Antibodies, Viral - biosynthesis / antibody response / Antigens, Viral / Antigens, Viral - genetics / Biological and medical sciences / Double-Blind Method / Encephalitis Virus, Japanese / Encephalitis Virus, Japanese - genetics / Encephalitis Virus, Japanese - immunology / Encephalitis, Japanese / Encephalitis, Japanese - immunology / Encephalitis, Japanese - prevention & control / Epidemiology. Vaccinations / Erythema / Erythema - etiology / Fundamental and applied biological sciences. Psychology / General aspects / Genetic Vectors / Humans / immune response / immunogenicity / Infectious diseases / Japanese encephalitis virus / Medical sciences / Microbiology / Neutralization Tests / Poxviridae / Poxviridae - genetics / Poxviridae - immunology / Poxvirus / Recombinant poxviruses / Safety / vaccines / Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies / Vaccines, Attenuated / Vaccines, Attenuated - adverse effects / Vaccines, Attenuated - immunology / Vaccines, Attenuated - pharmacology / Vaccines, Synthetic / Vaccines, Synthetic - adverse effects / Vaccines, Synthetic - immunology / Vaccines, Synthetic - pharmacology / Vaccinia / Vaccinia - immunology / Vaccinia immunity / Vaccinia virus / Viral Vaccines / Viral Vaccines - adverse effects / Viral Vaccines - immunology / Viral Vaccines - pharmacology / Virology