Bovine adenovirus-3 as a vaccine delivery vehicle

Ayalew, Lisanework E.; Kumar, Pankaj; Gaba, Amit; Makadiya, Niraj; Tikoo, Suresh K.

doi:10.1016/j.vaccine.2014.11.055

Cited by 11 publications

(7 citation statements)

References 88 publications

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“…Non-human adenoviruses can be used as alternative vaccine vectors, providing several advantages such as a limited host range and restricted replication in non-host species. By using bovine adenovirus type 3, a variety of antigens and cytokines were successfully expressed in vivo (Ayalew et al. 2015).…”

Section: Overview Of Empirical Resultsmentioning

confidence: 99%

On the stability of sequences inserted into viral genomes

Willemsen

Zwart

2019

Virus Evolution

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Viruses are widely used as vectors for heterologous gene expression in cultured cells or natural hosts, and therefore a large number of viruses with exogenous sequences inserted into their genomes have been engineered. Many of these engineered viruses are viable and express heterologous proteins at high levels, but the inserted sequences often prove to be unstable over time and are rapidly lost, limiting heterologous protein expression. Although virologists are aware that inserted sequences can be unstable, processes leading to insert instability are rarely considered from an evolutionary perspective. Here, we review experimental work on the stability of inserted sequences over a broad range of viruses, and we present some theoretical considerations concerning insert stability. Different virus genome organizations strongly impact insert stability, and factors such as the position of insertion can have a strong effect. In addition, we argue that insert stability not only depends on the characteristics of a particular genome, but that it will also depend on the host environment and the demography of a virus population. The interplay between all factors affecting stability is complex, which makes it challenging to develop a general model to predict the stability of genomic insertions. We highlight key questions and future directions, finding that insert stability is a surprisingly complex problem and that there is need for mechanism-based, predictive models. Combining theoretical models with experimental tests for stability under varying conditions can lead to improved engineering of viral modified genomes, which is a valuable tool for understanding genome evolution as well as for biotechnological applications, such as gene therapy.

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Section: Overview Of Empirical Resultsmentioning

confidence: 99%

On the stability of sequences inserted into viral genomes

Willemsen

Zwart

2019

Virus Evolution

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“…Recombinant human adenoviruses (HAdVs) can effectively deliver vaccine antigens in animals [ 3 , 31 ] but the large amount of recombinant HAdV-5 required to induce a protective immune response [ 31 ] is not compatible with the production of an economical vaccine for animals. Since non-human adenoviruses appear species specific, the development of species-specific adenovirus-based vectors may provide a better option for delivering vaccine antigens.…”

Section: Discussionmentioning

confidence: 99%

“…Recombinant adenoviral vectors have also been widely used for in vivo gene transfer because of their ability to enter many different cell types and efficiently express transgenes [ 2 ]. Although adenoviruses have been used to deliver vaccine antigens to cattle [ 1 ], we have focused on developing species-specific adenoviruses as vaccine-delivery vehicles [ 3 ]. Earlier, molecular characterization of bovine adenovirus 3 (BAdV-3) [ 4 ] led to the development of BAdV-3 as a vaccine vector for immunizing cattle [ 5 , 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

Bovine Adenovirus-3 Tropism for Bovine Leukocyte Sub-Populations

Khosa

Araya

Griebel

et al. 2020

Viruses

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A number of characteristics including lack of virulence and the ability to grow to high titers, have made bovine adenovirus-3 (BAdV-3) a vector of choice for further development as a vaccine-delivery vehicle for cattle. Despite the importance of blood leukocytes, including dendritic cells (DC), in the induction of protective immune responses, little is known about the interaction between BAdV-3 and bovine blood leukocytes. Here, we demonstrate that compared to other leukocytes, bovine blood monocytes and neutrophils are significantly transduced by BAdV404a (BAdV-3, expressing enhanced yellow green fluorescent protein [EYFP]) at a MOI of 1–5 without a significant difference in the mean fluorescence of EYFP expression. Moreover, though expression of some BAdV-3-specific proteins was observed, no progeny virions were detected in the transduced monocytes or neutrophils. Interestingly, addition of the “RGD” motif at the C-terminus of BAdV-3 minor capsid protein pIX (BAV888) enhanced the ability of the virus to enter the monocytes without altering the tropism of BAdV-3. The increased uptake of BAV888 by monocytes was associated with a significant increase in viral genome copies and the abundance of EYFP and BAdV-3 19K transcripts compared to BAdV404a-transduced monocytes. Our results suggest that BAdV-3 efficiently transduces monocytes and neutrophils in the absence of viral replication. Moreover, RGD-modified capsid significantly increases vector uptake without affecting the initial interaction with monocytes.

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“…For instance, bovine AdV-3 (BAdV-3), porcine AdV-3 (PAdV-3) and -5, canine AdV-2 (CAdV-2), fowl AdV-1 (FAdV-1), -8, -9, and -10 have been modified to respectively express homologous host-relevant antigens in an attempt to build affordable and effective vaccines. 143 , 144 , 145 , 146 , 147 , 148 In spite of this research effort, none of these approaches have led to the market introduction of any recombinant AdV-based veterinary vaccines. Currently, the only promising such vaccine candidate is a replication-deficient HAdV-5 vector expressing the relevant genes of the foot and mouth disease virus.…”

Section: Alternatives To Hadv-5 Vectorsmentioning

confidence: 99%

Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5–based Constructs

et al. 2016

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Recombinant vectors based on human adenovirus serotype 5 (HAdV-5) have been extensively studied in preclinical models and clinical trials over the past two decades. However, the thorough understanding of the HAdV-5 interaction with human subjects has uncovered major concerns about its product applicability. High vector-associated toxicity and widespread preexisting immunity have been shown to significantly impede the effectiveness of HAdV-5–mediated gene transfer. It is therefore that the in-depth knowledge attained working on HAdV-5 is currently being used to develop alternative vectors. Here, we provide a comprehensive overview of data obtained in recent years disqualifying the HAdV-5 vector for systemic gene delivery as well as novel strategies being pursued to overcome the limitations observed with particular emphasis on the ongoing vectorization efforts to obtain vectors based on alternative serotypes.

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Bovine adenovirus-3 as a vaccine delivery vehicle

Cited by 11 publications

References 88 publications

On the stability of sequences inserted into viral genomes

On the stability of sequences inserted into viral genomes

Bovine Adenovirus-3 Tropism for Bovine Leukocyte Sub-Populations

Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5–based Constructs

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