Development of chimpanzee adenoviruses as vaccine vectors: challenges and successes emerging from clinical trials

Capone, Stefania; D’Alise, Anna Morena; Ammendola, Virginia; Colloca, Stefano; Cortese, Riccardo; Nicosia, Alfredo; Folgori, Antonella

doi:10.1586/erv.13.15

Cited by 82 publications

(76 citation statements)

References 126 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%

“…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).…”

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confidence: 99%

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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%

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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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“…We show that compared to controls, heterologous PanAd3-RSV prime/MVA-RSV boost regimens protected calves against BRSV infection and reduced pulmonary pathology. Vaccines based on replication-incompetent ChAd and MVA vectors are capable of inducing a full spectrum of adaptive humoral and cell-mediated immune responses (6). This approach has been shown to be safe and highly immunogenic in humans as documented by results obtained in phase 1 clinical trials with candidate vaccines against hepatitis C, malaria, and Ebola (15,24,25).…”

Section: Discussionmentioning

confidence: 99%

Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections

Taylor

Thom

Capone³

et al. 2015

Sci. Transl. Med.

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Human respiratory syncytial virus (HRSV) is a major cause of lower respiratory tract disease in children and the elderly for which there is still no effective vaccine. We have previously shown that PanAd3-RSV, which is a chimpanzee adenovirus-vectored vaccine candidate that expresses a secreted form of the HRSV F protein together with the N and M2-1 proteins of HRSV, is immunogenic in rodents and nonhuman primates, and protects mice and cotton rats from HRSV challenge. Because the extent to which protection demonstrated in rodent models will translate to humans is unclear, we have exploited the calf model of bovine RSV (BRSV) infection, which mimics HRSV disease in children more closely than do experimental models of unnatural laboratory hosts, to evaluate the safety and efficacy of the PanAd3-RSV vaccine. We show that PanAd3-RSV alone and in combination with a modified vaccinia Ankara expressing the same HRSV antigens (MVA-RSV) induced neutralizing antibodies and cellular immunity in young seronegative calves and protected against upper and lower respiratory tract infection and pulmonary disease induced by heterologous BRSV challenge. There was no evidence either of enhanced pulmonary pathology or of enhanced respiratory disease in vaccinated calves after BRSV challenge. These findings support the continued evaluation of the vectored RSV vaccines in man.

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“…Pre-existing immunity can be circumvented by vectors based on viruses that circulate in non-human primates [63][64][65][66]. These viruses are closely related to their human counterparts but most humans lack neutralizing antibodies to simian viruses.…”

Section: Pre-existing Immune Responses To the Vaccine Carriermentioning

confidence: 99%

Viral vectors as vaccine carriers

Ertl

2016

Current Opinion in Virology

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Development of chimpanzee adenoviruses as vaccine vectors: challenges and successes emerging from clinical trials

Cited by 82 publications

References 126 publications

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

Efficacy of a virus-vectored vaccine against human and bovine respiratory syncytial virus infections

Viral vectors as vaccine carriers

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