Creation of a panel of vectors based on ape adenovirus isolates

Roy, Subhasish; Medina‐Jaszek, Angelica; Wilson, Matthew; Sandhu, Arbansjit K.; Calcedo, Roberto; Jiao, Lin; Wilson, James M.

doi:10.1002/jgm.1530

Cited by 34 publications

(27 citation statements)

References 15 publications

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“…ecombinant adenoviruses (Ads) are currently being explored as candidate vaccine vectors for multiple pathogens (1)(2)(3)(4)(5)(6), as a result of their safety profile, manufacturability, and ability to induce broad and strong immune responses (7)(8)(9)(10)(11)(12)(13)(14)(15)(16). Multiple human and chimpanzee adenovirus vectors have been developed to date (8,9,(11)(12)(13).…”

mentioning

confidence: 99%

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

Abbink

Maxfield

Ng’ang’a

et al. 2015

J Virol

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Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. The phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. Here we describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors. IMPORTANCEAlthough there have been substantial efforts in the development of vaccine vectors from human and chimpanzee adenoviruses, far less is known about rhesus monkey adenoviruses. In this report, we describe the isolation and vectorization of three novel rhesus monkey adenoviruses. These vectors exhibit virologic and immunologic characteristics that make them attractive as potential candidate vaccine vectors for both HIV-1 and other pathogens. R ecombinant adenoviruses (Ads) are currently being explored as candidate vaccine vectors for multiple pathogens (1-6), as a result of their safety profile, manufacturability, and ability to induce broad and strong immune responses (7-16). Multiple human and chimpanzee adenovirus vectors have been developed to date (8,9,(11)(12)(13). The majority of these adenovirus vectors are from species B, C, D, and E. Adenovirus vectors from avian, bovine, and other species have also been constructed, but their different genomic structures may necessitate the development of a novel manufacturing platform for clinical development (17, 18). Old World monkey adenoviruses have been hypothesized to be distinct from both human and chimpanzee adenoviruses and may offer unique advantages, such as the ability to more efficiently bypass preexisting immunity to human adenoviruses (12,(19)(20)(21)(22)(23)(24), while maintaining the genomic structure and growth properties of human adenoviruses.We isolated simian adenoviruses from fecal samples from rhesus monkeys (Macaca mulatta) that were positive for adenoviruses by metagenomics sequencing (25). We performed whole-genome sequencing of these novel adenoviruses and determined their phylogeny in comparison with that of other human and simian adenoviruses. The basic genetic structure of these novel rhesus monkey adenoviruses proved similar to that of human adenoviruses (7,16,26). We vectorized three rhesus monkey adenoviruses and then assessed humans in sub-Saharan Africa for seroprevalence of these adenoviruses and ...

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confidence: 99%

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

Abbink

Maxfield

Ng’ang’a

et al. 2015

J Virol

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“…Pan 6 vector demonstrated a better capacity than HAdV-5 vector in transduction of brain tumor cells and glioma cells, indicating that it is a promising vector candidate for the brain tumor therapy (Skog et al, 2007). Twenty E1-deleted vectors were generated from different AdVs isolated from chimpanzees, bonobos, and gorillas, of which 12 could be propagated, rescued, and expanded in HEK293 cells (Roy et al, 2011b). SAdV-7 (HAdV G species) was proposed for vectoring a few years earlier (Purkayastha et al, 2005b), and was subsequently constructed as an E1-deleted vector that could be complemented by HAdV-5 E1 genes in HEK293 cells (Roy et al, 2011a).…”

Section: Simian Adv Vectorsmentioning

confidence: 99%

Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors

et al. 2014

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Adenoviruses are efficient gene delivery vectors based on their ability to transduce a wide variety of cell types and drive high-level transient transgene expression. While there have been advances in modifying human adenoviral (HAdV) vectors to increase their safety profile, there are still pitfalls that need to be further addressed. Preexisting humoral and cellular immunity against common HAdV serotypes limits the efficacy of gene transfer and duration of transgene expression. As an alternative, nonhuman AdV (NHAdV) vectors can circumvent neutralizing antibodies against HAdVs in immunized mice and monkeys and in human sera, suggesting that NHAdV vectors could circumvent preexisting humoral immunity against HAdVs in a clinical setting. Consequently, there has been an increased interest in developing NHAdV vectors for gene delivery in humans. In this review, we outline the recent advances and limitations of HAdV vectors for gene therapy and describe examples of NHAdV vectors focusing on their immunogenicity, tropism, and potential as effective gene therapy vehicles.

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“…Simian adenoviruses provide a promising alternative, as they maintain the same safety profile as Ad5 [16, 18] and the level of anti-vector neutralizing activity of human sera has been found to be low [19]. In addition, the use of simian adenoviruses in Ebola Virus [20, 21], HIV [18], HCV [22], and malaria [23–26] vaccine candidates provides further support for the safety and utility of these vectors.…”

Section: Introductionmentioning

confidence: 99%

“…Here we evaluated the immunogenicity and protective efficacy of a heterologous Ad prime – protein boost vaccination regimen, testing three different doses of the simian adenovirus 36 (SAd36), a vector resistant to neutralizing anti-Ad5 antibodies [19]. This vector was engineered to express the synthetic PyCMP gene.…”

Section: Introductionmentioning

confidence: 99%

A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice

Fonseca¹,

McCaffery

Kashentseva

et al. 2017

Vaccine

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Malaria remains a considerable burden on public health. In 2015, the WHO estimates there were 212 million malaria cases causing nearly 429,000 deaths globally. A highly effective malaria vaccine is needed to reduce the burden of this disease. We have developed an experimental vaccine candidate (PyCMP) based on pre-erythrocytic (CSP) and erythrocytic (MSP1) stage antigens derived from the rodent malaria parasite P. yoelii. Our protein-based vaccine construct induces protective antibodies and CD4+ T cell responses. Based on evidence that viral vectors increase CD8+ T cell-mediated immunity, we also have tested heterologous prime-boost immunization regimens that included human adenovirus serotype 5 vector (Ad5), obtaining protective CD8+ T cell responses. While Ad5 is commonly used for vaccine studies, the high prevalence of pre-existing immunity to Ad5 severely compromises its utility. Here, we report the use of the novel simian adenovirus 36 (SAd36) as a candidate for a vectored malaria vaccine since this virus is not known to infect humans, and it is not neutralized by anti-Ad5 antibodies. Our study shows that the recombinant SAd36PyCMP can enhance specific CD8+ T cell response and elicit similar antibody titers when compared to an immunization regimen including the recombinant Ad5PyCMP. The robust immune responses induced by SAd36PyCMP are translated into a lower parasite load following P. yoelii infectious challenge when compared to mice immunized with Ad5PyCMP.

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Creation of a panel of vectors based on ape adenovirus isolates

Abstract: E1-deleted adenovirus vectors can be created from a wide variety of ape adenoviruses that can be rescued and propagated in HEK 293 cells. The prevalence of pre-existing antibodies that can neutralize these adenoviruses in human populations is low.

Cited by 34 publications

References 15 publications

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

Circumventing Antivector Immunity: Potential Use of Nonhuman Adenoviral Vectors

A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice

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