Clinical Assessment of a Novel Recombinant Simian Adenovirus ChAdOx1 as a Vectored Vaccine Expressing Conserved Influenza A Antigens

Antrobus, Richard; Coughlan, Lynda; Berthoud, Tamara; Dicks, Matthew D. J.; Hill, Adrian V. S.; Lambe, Teresa; Gilbert, Sarah C.

doi:10.1038/mt.2013.284

Cited by 176 publications

(199 citation statements)

References 40 publications

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“…Fecal shedding still occurs so a vaccine approach has not yet been developed that will eliminate MAP infection from food animals. Concerns over the pathogenicity of MAP in humans have supported the progress of planned Phase 1 and Phase 2a clinical trials to determine the safety and efficacy in humans of a vaccine that encodes two secreted and two surface proteins of MAP [113,114]. …”

Section: Future Considerationsmentioning

confidence: 99%

Mycobacterium paratuberculosis as a cause of Crohn’s disease

McNees

Markesich

Zayyani

et al. 2015

Expert Review of Gastroenterology & Hepatology

113

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SUMMARY Crohn's disease is a chronic inflammatory bowel disease of unknown cause, affecting approximately 1.4 million North American people. Due to the similarities between Crohn's disease and Johne’s disease, a chronic enteritis in ruminant animals caused by Mycobacterium avium paratuberculosis (MAP) infection, MAP has long been considered to be a potential cause of Crohn's disease. MAP is an obligate intracellular pathogen that cannot replicate outside of animal hosts. MAP is widespread in dairy cattle and because of environmental contamination and resistance to pasteurization and chlorination, humans are frequently exposed through contamination of food and water. MAP can be cultured from the peripheral mononuclear cells from 50 to 100% of patients with Crohn's disease, and less frequently from healthy individuals. Association does not prove causation. We discuss the current data regarding MAP as a potential cause of Crohn's disease and outline what data will be required to firmly prove or disprove the hypothesis.

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Section: Future Considerationsmentioning

confidence: 99%

Mycobacterium paratuberculosis as a cause of Crohn’s disease

McNees

Markesich

Zayyani

et al. 2015

Expert Review of Gastroenterology & Hepatology

113

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“…The construction of ChAdOx1 NP+M1 has been described previously (13). Details of the viral vectored vaccines used in these studies are as described in Table I :…”

Section: Recombinant Chad and Mva Vaccinesmentioning

confidence: 99%

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Chinnakannan

Mullarkey

Ulaszewska

et al. 2017

The Journal of Immunology

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Abstract:Seasonal influenza viruses (IAV) are a common cause of acute respiratory illness worldwide and generate a significant socio-economic burden. IAV rapidly mutate, necessitating annual vaccine reformulation as traditional vaccines do not typically induce broad-spectrum immunity. In addition to seasonal infections, emerging pandemic influenza viruses present a continued threat to global public health. Pandemic influenza viruses have consistently higher attack rates and are typically associated with greater mortality as compared to seasonal strains. Ongoing strategies to improve vaccine efficacy typically focus on providing broad-spectrum immunity, and while both B and T cells can mediate heterosubtypic responses, typical vaccine development will augment either humoral or cellular immunity. However, multipronged approaches, targeting several antigens, may limit the generation of viral escape mutants. There are few vaccine platforms that can deliver multiple antigens and generate robust cellular and humoral immunity. In this work, we describe a novel vaccination strategy, tested pre-clinically in mice, for the delivery of novel bivalent viral-vectored vaccines. Here, we show this strategy elicits potent T cell responses toward highly conserved internal antigens, whilst simultaneously inducing high levels of antibodies towards hemagglutinin (HA). Importantly, these humoral responses generate longlived plasma cells and generate antibodies capable of neutralising variant HA-expressing pseudotyped lentiviruses. Significantly, these novel viral-vectored vaccines induce strong immune responses capable of conferring protection in a stringent influenza A virus challenge.Thus, this vaccination regimen induces lasting efficacy toward influenza. Importantly, the simultaneous delivery of dual antigens may alleviate the selective pressure thought to potentiate antigenic diversity in avian influenza viruses.

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“…For example, Ad26 vectors from Ad subgroup D and Ad35 vectors from Ad subgroup B have recently been developed and tested in Phase I clinical trials 21–26 . Similarly, various promising chimpanzee Ad vectors have recently been produced and tested in Phase I clinical studies 27–30 .…”

Section: Novel Serotype Ad Vectorsmentioning

confidence: 99%

Novel vaccine vectors for HIV-1

Barouch

Picker

2014

Nat Rev Microbiol

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The ultimate solution to the global HIV-1 epidemic will probably require the development of a safe and effective vaccine. Multiple vaccine platforms have been evaluated in both preclinical and clinical trials, but, given the disappointing results of the clinical efficacy studies so far, novel vaccine approaches are needed. In this Opinion article, we discuss the scientific basis and clinical potential of novel adenovirus and cytomegalovirus vaccine vectors for HIV-1 as two contrasting, but potentially complementary, vector approaches. Both of these vector platforms have demonstrated partial protection against stringent simian immunodeficiency virus challenges in rhesus monkeys using different immunological mechanisms.

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Clinical Assessment of a Novel Recombinant Simian Adenovirus ChAdOx1 as a Vectored Vaccine Expressing Conserved Influenza A Antigens

Cited by 176 publications

References 40 publications

Mycobacterium paratuberculosis as a cause of Crohn’s disease

Mycobacterium paratuberculosis as a cause of Crohn’s disease

Novel Bivalent Viral-Vectored Vaccines Induce Potent Humoral and Cellular Immune Responses Conferring Protection against Stringent Influenza A Virus Challenge

Novel vaccine vectors for HIV-1

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