First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Adenovirus Serotype 26 HIV-1 Env Vaccine (IPCAVD 001)

Baden, Lindsey R.; Walsh, Stephen R.; Seaman, Michael S.; Tucker, Robert; Krause, Karl‐Heinz; Patel, Alka; Johnson, Jennifer A.; Kleinjan, Jane A.; Yanosick, Katherine E.; Perry, James; Zablowsky, Elise; Abbink, Peter; Peter, Lauren; Iampietro, M. Justin; Cheung, Anthony P.; Pau, Maria Grazia; Weijtens, Mo; Goudsmit, Jaap; Swann, Edith; Wolff, Mark; Loblein, Hayley; Dolin, Raphael; Barouch, Dan H.

doi:10.1093/infdis/jis670

Cited by 147 publications

(146 citation statements)

References 29 publications

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“…Table 1 shows the source and growth characteristics of these simian adenoviruses. The novel rhesus monkey adenovirus vectors were viable and grew to high titers, with ratios ranging from 3 to 30 vp/PFU, similar to those seen with human adenovirus vectors (data not shown), suggesting that these vectors might be suitable for large-scale production in the standard cell lines that are currently being utilized to manufacture human adenovirus vaccine vectors (1,35). We also constructed vectors that expressed various transgenes, including HIV/SIV Gag, Pol, Env, luciferase, and eGFP (data not shown), suggesting the generalizability of these vector platforms.…”

Section: Resultsmentioning

confidence: 63%

“…A major research focus over the past several years has been the development of novel adenovirus vaccine vectors, apart from Ad5, that exhibit a lower seroprevalence in humans in the developing world. Most efforts to date have focused on alternative serotypes of human adenovirus vectors and chimpanzee adenovirus vectors, both of which are currently being evaluated in clinical trials (1,13,43,44). However, these vectors still show a degree of seroprevalence in the developing world, and human and chimpanzee adenoviruses exhibit interdigitating phylogeny.…”

Section: Discussionmentioning

confidence: 99%

“…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%

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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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Section: Resultsmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

mentioning

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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“…120,121 Ad26 and Ad35 studies have shown potential in phase I/II human vaccine trials. [122][123][124][125] A recent randomized, double-blind, placebo-controlled trial in 218 healthy adults using Ad26. EnvA.01 and Ad35.Env vectors in both homologous and heterologous combinations elicited humoral and cellular immune responses in nearly all participants.…”

Section: New Vectorsmentioning

confidence: 99%

Progress in HIV vaccine development

Hsu

O’Connell

2017

Human Vaccines & Immunotherapeutics

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“…There are approximately 60 different types of Ad divided into 7 species (A-G) (Wy Ip and Qasim, 2013). Researchers, including ourselves, have begun to look into the use of low-seroprevalent Ads as alternative viral vectored vaccines (Abbink et al, 2007;Waddington et al, 2008;Schuldt et al, 2012;Teigler et al, 2012;Zahn et al, 2012;Baden et al, 2013;Weaver, 2013;Weaver and Barry, 2013). While these alternative viral vectors may have a lower seroprevalence, the differences in their biology as compared with Ad5 have started to come into question.…”

Section: Introductionmentioning

confidence: 99%

CD46-Mediated Transduction of a Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy

et al. 2014

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The high levels of preexisting immunity against Adenovirus type 5 (Ad5) have deemed Ad5 unusable for translation as a human vaccine vector. Low seroprevalent alternative viral vectors may be less impacted by preexisting immunity, but they may also have significantly different phenotypes from that of Ad5. In this study we compare species D Ads (26, 28, and 48) to the species C Ad5. In vitro transduction studies show striking differences between the species C and D viruses. Most notably, Ad26 transduced human dendritic cells much more effectively than Ad5. In vivo imaging studies showed strikingly different transgene expression profiles. The Ad5 virus was superior to the species D viruses in BALB/c mice when delivered intramuscularly. However, the inverse was true when the viruses were delivered mucosally via the intranasal epithelia. Intramuscular transduction was restored in mice that ubiquitously expressed human CD46, the primary receptor for species D viruses. We analyzed both species C and D Ads for their ability to induce prophylactic immunity against influenza in the CD46 transgenic mouse model. Surprisingly, the species D vaccines again failed to induce greater levels of protective immunity as compared with the species C Ad5 when delivered intramuscularly. However, the species D Ad vaccine vector, Ad48, induced significantly greater protection as compared with Ad5 when delivered mucosally via the intranasal route in CD46 transgenic mice. These data shed light on the complexities between the species and types of Ad. Our findings indicate that more research will be required to identify the mechanisms that play a key role in the induction of protective immunity induced by species D Ad vaccines.

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First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Adenovirus Serotype 26 HIV-1 Env Vaccine (IPCAVD 001)

Abstract: NCT00618605.

Cited by 147 publications

References 29 publications

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

Progress in HIV vaccine development

CD46-Mediated Transduction of a Species D Adenovirus Vaccine Improves Mucosal Vaccine Efficacy

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