Generation and evaluation of a recombinant modified vaccinia virus Ankara vaccine for rabies

Abstract

Abstract

A New Rabies Vaccine Based on a Recombinant Orf Virus (Parapoxvirus) Expressing the Rabies Virus Glycoprotein

“…One important demand for improved rabies vaccines is the induction of a solid protective immunity after a single vaccine inoculation, which can be achieved with 10 7 PFU of D1701-V-RabG. Dose-dependent reduction in protection rates was accompanied by a reduction of VNA titers as reported for other recombinant rabies vaccines (22,33,35,58). The presented data, however, do not allow an unambiguous correlation between protection and magnitude of VNA titers in mice.…”

“…VACV vector strain MVA expressing RabG failed to elicit detectable VNA even after booster with high doses of this recombinant and consequently did not protect against RABV challenge infection. Similarly, V-RG or a recombinant derived from the VACV strain Western Reserve mediated only partial protection against mild RABV challenge infection (33). Nevertheless, those vaccines were found effective in other animals by oral application, indicating some limitations of the murine model for evaluating the efficacy of the oral vaccination and, therefore, encourages testing the oral vaccination efficacy of D1701-V-RabG in wildlife reservoirs.…”

“…A safer, attenuated, and replication-deficient variant of VACV vector is represented by the modified vaccinia virus Ankara (MVA) strain. The RabG-expressing MVA recombinant, however, was found to be less immunogenic than V-RG and did not mediate complete protection against RABV, and dogs were not protected by oral administration (14,33). Other poxviral vectors have been used to generate host-restricted recombinant live vaccines against rabies, such as raccoon poxvirus (34), canary poxvirus (35), fowl poxvirus (36), or capripoxvirus (37).…”

A Novel Rabies Vaccine Based on a Recombinant Parainfluenza Virus 5 Expressing Rabies Virus Glycoprotein

“…During the past decade, a number of recombinant rabies vaccine candidates based on live attenuated RABV or recombinant viruses expressing RABV G (such as V-RG) have been developed as potential alternatives to current rabies vaccines (17,29,(32)(33)(34)(35). While some of the vaccine candidates generated protective immunity when administered via the i.m.…”

Attenuated and Replication-Competent Vaccinia Virus Strains M65 and M101 with Distinct Biology and Immunogenicity as Potential Vaccine Candidates against Pathogens

“…The first generation of vaccines against cancer, HIV/AIDS, and other infectious diseases was based on replication-competent strains of VACV such as WR, Wyeth, Lister, Copenhagen, and Tian Tan (62,63); due to safety concerns, however, most of the candidates currently assayed in vaccine studies are nonreplicative VACV vectors such as canarypox, fowlpox, MVA, or NYVAC (3,5). Although highly attenuated vectors are capable of inducing protective immunity against a variety of pathogens, their limitation in replication capacity reduces their potential to induce immune responses similarly to replicationcompetent counterparts (64)(65)(66)(67). In order to find an equilibrium between safety and replication, different poxviruses with an intermediate phenotype are being sought.…”