A Novel Chimpanzee Adenovirus Vector with Low Human Seroprevalence: Improved Systems for Vector Derivation and Comparative Immunogenicity

Dicks, Matthew D. J.; Spencer, Alexandra J.; Edwards, Nick J.; Wadell, Göran; Bojang, Kalifa; Gilbert, Sarah C.; Hill, Adrian V. S.; Cottingham, Matthew G.

doi:10.1371/journal.pone.0040385

Cited by 340 publications

(411 citation statements)

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“…Investigations of adenovirus biology have led to Nobel Prize-winning discoveries in mRNA splicing and to important progress in the understanding of antigen presentation to T cells (8). Moreover, the ability of adenoviruses to infect many cell types facilitated their exploitation as vectors for gene delivery to generate new tools for innovative treatments of important diseases, such as cancer and cardiovascu-lar disorders (9)(10)(11)(12)(13). Hence, adenoviruses are highly versatile organisms with a broad spectrum of clinical roles and applications.…”

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confidence: 99%

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

2014

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SUMMARY Human adenoviruses (HAdVs) are an important cause of infections in both immunocompetent and immunocompromised individuals, and they continue to provide clinical challenges pertaining to diagnostics and treatment. The growing number of HAdV types identified by genomic analysis, as well as the improved understanding of the sites of viral persistence and reactivation, requires continuous adaptions of diagnostic approaches to facilitate timely detection and monitoring of HAdV infections. In view of the clinical relevance of life-threatening HAdV diseases in the immunocompromised setting, there is an urgent need for highly effective treatment modalities lacking major side effects. The present review summarizes the recent progress in the understanding and management of HAdV infections.

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confidence: 99%

Adenovirus Infections in Immunocompetent and Immunocompromised Patients

2014

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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).…”

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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%

“…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.…”

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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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“…Protection against acquisition of infection correlated with vaccine-elicited binding (although not with V2 responses), neutralizing, and functional non-neutralizing antibodies, suggesting that the coordinated activity of multiple antibody functions may contribute to protection against difficult-to-neutralize viruses. 123 In-depth analysis of the HVTN 505 results and underlying immune responses and sieve analysis might inform the development of other non-Ad5 rare serotype adenoviruses vectors such as Ad26, Ad35, 124 or ChAdV63 125 and more generally of T-cellinducing vaccine strategies. DNA administered intramuscularly by electroporation augmented elicited T-cell immune responses compared with needle injection.…”

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confidence: 99%