A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes

Yan, Lei; Zhao, Zhiguang; Xue, Xiaolin; Zheng, Wenwen; Xu, Tong; Liu, Lele; Tian, Li; Wang, Xianwei; He, Hongbin; Zheng, Xiaodong

doi:10.3389/fmicb.2020.01070

Cited by 15 publications

(9 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…in Cynomolgus Macaques. The titre of RVNA ≥0.5 IU/ml in sera was considered to be sufficient for protection from rabies infections, and the RVNAs are mainly specific to its surface G protein [ 44 ]. Thus, the AAV9 was a high-efficiency vector for gene delivery of the RABV G in mice and in NHPs.…”

Section: Discussionmentioning

confidence: 99%

Recombinant adeno-associated virus serotype 9 AAV-RABVG expressing a Rabies Virus G protein confers long-lasting immune responses in mice and non-human primates

Shi

Tian

Zheng

et al. 2022

Emerging Microbes & Infections

Self Cite

View full text Add to dashboard Cite

Three or four intramuscular doses of the inactivated human rabies virus vaccines are needed for pre- or post-exposure prophylaxis in humans. This procedure has made a great contribution to prevent human rabies deaths, which bring huge economic burdens in developing countries. Herein, a recombinant adeno-associated virus serotype 9, AAV9-RABVG, harbouring a RABV G gene, was generated to serve as a single dose rabies vaccine candidate. The RABV G protein was stably expressed in the 293T cells infected with AAV9-RABVG. A single dose of 2 × 10 11 v.p. of AAV9-RABVG induced robust and long-term positive seroconversions in BALB/c mice with a 100% survival from a lethal RABV challenge. In Cynomolgus Macaques vaccinated with a single dose of 1 × 10 13 v.p. of AAV9-RABVG, the titres of rabies VNAs increased remarkably from 2 weeks after immunity, and maintained over 31.525 IU/ml at 52 weeks. More DCs were activated significantly for efficient antigen presentations of RABV G protein, and more B cells were activated to be responsible for antibody responses. Significantly more RABV G specific IFN-γ-secreting CD4+ and CD8+ T cells, and IL-4-secreting CD4+ T cells were activated, and significantly higher levels of IL-2, IFN-γ, IL-4, and IL-10 were secreted to aid immune responses. Overall, the AAV9-RABVG was a single dose rabies vaccine candidate with great promising by inducing robust, long-term humoral responses and both Th1 and Th2 cell-mediated immune responses in mice and non-human primates.

show abstract

Section: Discussionmentioning

confidence: 99%

Recombinant adeno-associated virus serotype 9 AAV-RABVG expressing a Rabies Virus G protein confers long-lasting immune responses in mice and non-human primates

Shi

Tian

Zheng

et al. 2022

Emerging Microbes & Infections

Self Cite

View full text Add to dashboard Cite

show abstract

“…There have been recent experimental vaccines produced using other vectors, such as a replication-defective human adenovirus that expresses the H protein of CDV. This experimental vaccine was shown to produce a humoral immune response in foxes (mean VN titer of 1:38 at 4 weeks post-vaccination), and provided protection against a lethal challenge four weeks after a single intramuscular injection with a very high dose (10 9 green fluorescent units of the vaccine virus) [ 86 ]. This vectored vaccine is bivalent- also expresses a protein of rabies virus, but this vaccine is missing the more conserved F protein of CDV that has been demonstrated to elicit a neutralizing response against more divergent CDV strains [ 85 ].…”

Section: Development Of a New Vaccinementioning

confidence: 99%

Canine Distemper Virus in Endangered Species: Species Jump, Clinical Variations, and Vaccination

Wilkes

2022

Pathogens

View full text Add to dashboard Cite

Canine morbillivirus (Canine distemper virus, CDV) is the cause of distemper in a large number of different species, some of which are endangered. The clinical outcome associated with infection is variable and based on many factors, including the host species, the immune response of the individual animal to the infection, and variation in virus tropism and virulence. Unfortunately, the viral characteristics associated with virulence versus attenuation are not fully characterized, nor are the specific mutations that allow this virus to easily move and adapt from one species to another. Due to its wide host range, this virus is difficult to manage in ecosystems that are home to endangered species. Vaccination of the domestic dog, historically considered the reservoir species for this virus, at dog-wildlife interfaces has failed to control virus spread. CDV appears to be maintained by a metareservoir rather than a single species, requiring the need to vaccinate the wildlife species at risk. This is controversial, and there is a lack of a safe, effective vaccine for nondomestic species. This review focuses on topics that are paramount to protecting endangered species from a stochastic event, such as a CDV outbreak, that could lead to extinction.

show abstract

“…As a research hotspot in recent years, the recombinant live vector recombinant vaccine of CSF is a novel vaccine prepared by recombining the virus antigen gene into a live vector that can express exogenous virus protein, which can stimulate the body to produce a specific immune response (Wei et al, 2021). At present, the structure and function of the adenovirus genome have been studied thoroughly; meanwhile, human type 5 nonreplicating adenovirus vectors have attracted researchers' attention because of their safety, wide host range and stability (Zhu et al, 2017;Yan et al, 2020). Previous studies have shown that adenovirus vectors can induce strong specific cellular and humoral immune responses, which are widely used in the construction of new vaccines against severe zoonotic diseases (Gabitzsch et al, 2011;Lapuente et al, 2018;Zhang et al, 2018).…”

Section: A B Cmentioning

confidence: 99%

“…In addition, human replication-deficient adenovirus type 5 live vector CSF vaccine and chimeric CSFV vaccine can induce complete immune protection. Adenovirus vector vaccines have been the mainstream research direction of CSF vaccines, due to the replication deficiency of adenovirus vectors, providing double effects with the safety of inactivated vaccines and the efficacy of live vaccines (Yan et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Immunogenicity of the recombinant adenovirus fusion-expressing E0-E2 gene of the classical swine fever virus

Zhang¹,

Yin

Qin

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

Adenovirus vector vaccines have been the mainstream research direction of CSF vaccines, due to the replication deficiency of adenovirus vectors, achieving double effects with the safety of inactivated vaccines and the efficacy of live vaccines. Therefore, the E0 and E2 genes were expressed by an adenovirus vector, a recombinant adenovirus E0-E2 (rAd-E0-E2) vaccine was constructed, and the minimum immunization dose and immune duration period were determined in this study. Forty healthy piglets were randomly divided into 8 groups (n = 5). Groups 1 ~ 5 were used to determine the minimum immunization dose, and 5 groups were inoculated with rAd-E0-E2 at different immune doses. Serum was collected at 7 d and 14 d after immunization to detect CSFV antibodies by ELISA, and piglets were challenged at 7 d post immunization. Groups 6 ~ 8 were immunized with 1 dose of rAd-E0-E2, the CSFV live attenuated vaccine C strain and saline to identify the immune duration period. Serum was collected at different time points after immunization, CSFV antibodies were detected by ELISA, and piglets were challenged at 8 months post immunization. Meanwhile, temperature, clinical symptoms and pathology were observed. The results of groups 1 ~ 5 showed that 1 piglet was protected after challenge, and 4 piglets exhibited high fever retention, typical CSFV symptoms and tissue lesions in the 1/50 dose group, whereas no clinical symptoms were observed in the 1/10 dose, 1/5 dose or 1 dose groups with 5/5 protection after challenge. The minimum dose was determined as 1/10 dose. The results of groups 6 ~ 8 showed that all piglets survived after challenge, but the antibody level of the rAd-E0-E2 strain was higher than that of the C strain at 8 months post immunization, and all piglets in the negative group developed the disease process after challenge. Overall, the minimum immunization dose of rAd-E0-E2 was 1/10 dose (3.16 × 106.0 IFU) and the minimum immune dose was determined to be 1 dose (3.16 × 107.0 IFU) to achieve the expected effects. The immune duration period of piglets immunized with 1 dose of rAd-E0-E2 was at least 8 months.

show abstract

A Bivalent Human Adenovirus Type 5 Vaccine Expressing the Rabies Virus Glycoprotein and Canine Distemper Virus Hemagglutinin Protein Confers Protective Immunity in Mice and Foxes

Cited by 15 publications

References 44 publications

Recombinant adeno-associated virus serotype 9 AAV-RABVG expressing a Rabies Virus G protein confers long-lasting immune responses in mice and non-human primates

Recombinant adeno-associated virus serotype 9 AAV-RABVG expressing a Rabies Virus G protein confers long-lasting immune responses in mice and non-human primates

Canine Distemper Virus in Endangered Species: Species Jump, Clinical Variations, and Vaccination

Immunogenicity of the recombinant adenovirus fusion-expressing E0-E2 gene of the classical swine fever virus

Contact Info

Product

Resources

About