A hexavalent Coxsackievirus B vaccine is highly immunogenic and has a strong protective capacity in mice and nonhuman primates

Abstract

Coxsackievirus B (CVB) enteroviruses are common human pathogens known to cause severe diseases including myocarditis, chronic dilated cardiomyopathy, and aseptic meningitis. CVBs are also hypothesized to be a causal factor in type 1 diabetes. Vaccines against CVBs are not currently available, and here we describe the generation and preclinical testing of a novel hexavalent vaccine targeting the six known CVB serotypes. We show that the vaccine has an excellent safety profile in murine models and nonhuman primates and that it induces strong neutralizing antibody responses to the six serotypes in both species without an adjuvant. We also demonstrate that the vaccine provides immunity against acute CVB infections in mice, including CVB infections known to cause virus-induced myocarditis. In addition, it blocks CVB-induced diabetes in a genetically permissive mouse model. Our preclinical proof-of-concept studies demonstrate the successful generation of a promising hexavalent CVB vaccine with high immunogenicity capable of preventing CVB-induced diseases.

Multiplexed High-Throughput Serological Assay for Human Enteroviruses

“…Information on cross-reactivity could be important for studying prototype vaccines’ responses, or if aiming to produce more accurate assays by reducing cross-reactivity. In recent years the interest in vaccinating against enteroviruses that cause chronic diseases have gained more momentum and prototype vaccines are being developed [ 34 , 35 ]. One major source of cross-reactivity between enterovirus antibodies is the VP1 N -terminal enterovirus group-specific immunodominant epitope; however, it is not a neutralizing one [ 18 ].…”

Prevention of Type 1 Diabetes: Past Experiences and Future Opportunities

“…However, viral vaccines or anti-viral drugs have never been tested, and now they have become attractive candidates to be studied in clinical prevention trials. In animal models, the vaccine protected mice infected with CVB from developing virus-induced T1D [28]. However, the study using the viral vaccine as preventive therapy has not been conducted in humans.…”

“…In these animals, the vaccine-induced antibodies to CVB, suggesting it could protect against the virus. The clinical studies testing the vaccine against CVB in human subjects are on the horizon [28]. The CVB vaccine could be effective for the primary prevention of T1D by halting an induction of beta-cell autoimmunity.…”

Genetic Susceptibility of the Host in Virus-Induced Diabetes

“…It is suggested that even in a host background prone to autoimmunity, the antiviral defense in β-cells plays a role in preventing VID onset. The Socs-1 Tg NOD mice have been used as a model animal to verify the effects of vaccination [120,121].…”