Immunisation of common marmosets with vaccinia virus expressing Epstein-Barr virus (EBV) gp340 and challenge with EBV

Abstract

Epstein-Barr virus (EBV) is the cause of infectious mononucleosis and is associated with a variety of life-threatening diseases in humans. Therefore the development of an effective vaccine is an important objective. Many of the initial studies of vaccine efficacy analyse the ability of vaccine preparations to prevent the induction of lymphomas in cottontop tamarins by the B95-8 strain of EBV. We used a vaccinia virus recombinant expressing gp340, vMA1, tested previously in the cotton-top tamarin, to evaluate a common marmoset model in which the challenge virus, M81, resembles more closely the wild-type strains of EBV in the general population than does the standard B95-8 strain. We characterised the M81 strain of EBV with respect to the sequence of its gp340/220 gene and in regard to the presence of a region deleted in B95-8. Replication of the challenge virus in the group vaccinated with vMA1 was decreased when compared to control groups.

Epstein Barr Virus: Development of Vaccines and Immune Cell Therapy for EBV-Associated Diseases

“…EBV gp350 is the most abundant EBV envelope protein, and about half of the EBV neutralizing activity in EBV seropositive human sera is against gp350 (7,161). Purified or recombinant gp350 was shown to protect cotton top tamarins from lymphoma caused by EBV infection, and similar results were reported with adenovirus or vaccinia virus expressing gp350 (69)(70)(71)(72)(73)(74)(75)(76). Phase I and II studies of a recombinant gp350 produced in Chinese hamster ovary cells showed that the recombinant gp350 induced neutralizing antibodies in humans in 70% of the subjects, and reduced the rate of infectious mononucleosis by 78% in the vaccinated subjects but did not prevent EBV infection (156,167).…”

Four Decades of Prophylactic EBV Vaccine Research: A Systematic Review and Historical Perspective

“…Viral vectors have the advantage of possessing intrinsic immune-stimulating capabilities and thus do not require administration with adjuvants; in addition, they can be combined with VLP platforms to produce VLPs in vivo ( 142 – 144 ). The 6 pre-clinical EBV vaccine studies using viral vectors tested measles virus ( 55 ), adenovirus ( 64 ), and vaccinia virus vectors ( 57 , 61 , 70 , 75 ) ( Table 3 ); the latter was also tested in one of the 4 EBV vaccine clinical trials [( 83 ), Table 4 ]. In these studies, the vectors were engineered to express single antigens, but viral vectors with the necessary genetic insert capacity can be engineered to express multiple antigens.…”

Urgency and necessity of Epstein-Barr virus prophylactic vaccines

“…As different approaches to gp350-based EBV vaccination, vaccinia virus and adenovirus were used as viral vectors to express gp350. The WR strain of vaccinia virus expressing gp350 (VV-gp350) induced humoral immune responses in rabbits, cottontop tamarins, and common marmosets 68 , 69 , 73 . It is remarkable that although no anti-gp350 antibodies and low levels of neutralizing antibodies were detected in cottontop tamarins inoculated with VV-gp350, three out of four animals were still free of lymphoma after an EBV challenge with a dose of 10 5.3 lymphocytes-transforming doses that cause tumors in 100% of unvaccinated tamarins 73 .…”

“…four times at a 4-week interval B95-8 3/5 were free of lymphoma after 100% tumorigenesis dose challenge 60 1996 Common marmosets Recombinant vaccinia virus expressing gp350 i.d. twice at a 5-week interval M81 Replication of the challenge virus was decreased 69 1998 Common marmosets recombinant gp350 with BPV + alum i.m. three times at a 4-week interval M81 Replication of the challenge virus was decreased 55 None there is no challenge experiment, ADCC antibody-dependent cell-mediated cytotoxicity.…”