PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials

Malcolm, Bruce A.; Aerts, Caroline Anne; Dubois, Kristof; Geurts, Frederik Joris; Mariën, Kris; Rusch, Sarah; Dijck, Alex Henri Van; Verloes, René; Vingerhoets, Johan

doi:10.1016/j.antiviral.2018.03.005

Cited by 8 publications

(9 citation statements)

References 32 publications

(35 reference statements)

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“…A modified poly I:C has been shown to be safe in Phase I trials in HIV-infected people on antiretroviral therapy ( Saxena et al, 2019 ). Also in clinical trial, a proprietary poly I:C vaccine administered IN was found to be effective in prevention of infection by rhinovirus and influenza A ( Malcolm et al, 2018 ). IN administration is preferred for some vaccines, eliciting better responses than intramuscular injection in some cases ( Hoft et al, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

Prevention and treatment of HIV infection and cognitive disease in mice by innate immune responses

Dong

Borjabad

Kelschenbach

et al. 2020

Brain, Behavior, & Immunity - Health

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HIV associated neurocognitive impairment afflicts roughly half of infected individuals on antiretroviral therapy. This disease currently has no treatment. We have previously shown that type I interferon is induced by and partially controls infection and neuropathogenesis in mice infected by chimeric HIV, EcoHIV. Here we investigate the intentional ligation of the pattern recognition receptor Toll-like receptor 3 (TLR3) by polyinosinic-polycytidylic acid (poly I:C) for its ability to prevent or control infection and associated cognitive disease in EcoHIV infected mice. We tested topical, injection, and intranasal application of poly I:C in mice during primary infection through injection or sexual transmission or in established infection. We measured different forms of HIV DNA and RNA in tissues by real-time PCR and the development of HIV-associated cognitive disease by the radial arm water maze behavioral test. Our results indicate that poly I:C blocks primary EcoHIV infection of mice prior to reverse transcription and reduces established EcoHIV infection. Prevention or control of viral replication by poly I:C prevents or reverses HIV associated cognitive disease in mice. These findings indicate that poly I:C or other innate immune agonists may be useful in control of HIV cognitive disease.

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Section: Discussionmentioning

confidence: 99%

Prevention and treatment of HIV infection and cognitive disease in mice by innate immune responses

Dong

Borjabad

Kelschenbach

et al. 2020

Brain, Behavior, & Immunity - Health

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“…Two PrEP-001 human clinical trials administering powdered poly(I:C) i.n. twice, 48 and 24 h prior to challenge with either rhinovirus or influenza A virus, showed reduced development of clinical illness and symptoms [10]. In another study, IFN-β-1a was i.n.…”

Section: Discussionmentioning

confidence: 94%

“…Modern pharmaceutical design and engineering has made it possible to synthetically design TLR agonists and, combined with novel delivery techniques, these can now be safely delivered to mucosal surfaces, which permits clinical testing. In recent clinical trials, intranasal delivery of the TLR3 agonist polyinosinic:polycytidylic acid [poly(I:C)], a synthetic dsRNA structurally similar to virus dsRNA, stimulated IFN-I production and significantly protected against Rhinovirus and Influenza virus infections in humans [10]. This immune prophylaxis was safe and well-tolerated.…”

Section: Introductionmentioning

confidence: 99%

A Novel Prophylaxis Strategy Using Liposomal Vaccine Adjuvant CAF09b Protects against Influenza Virus Disease

Zimmermann

Schmidt

Trebbien

et al. 2022

IJMS

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The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future respiratory virus pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF®09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b liposomes as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b liposomes to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I-related gene expression. When CAF09b liposomes were administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although the virus was still detectable in the lungs. However, when CAF09b liposomes were administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.

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“…Two PrEP-001 human clinical trials administering powdered poly(I:C) i.n. twice 48 and 24 h prior to challenge with either rhinovirus or influenza A virus showed reduced development of clinical illness and symptoms (10). In another study, IFNβ-1a was intranasally dosed once daily up to 14 days to patients hospitalized with Covid-19 symptoms, which was well tolerated and resulted in greater chances of recovery compared to a placebo group (24).…”

Section: Discussionmentioning

confidence: 99%

“…Modern pharmaceutical design and engineering has made it possible to synthetically design TLR agonists and, combined with novel delivery techniques, these can now be delivered safely to mucosal surfaces, which permits clinical testing. In recent clinical trials intranasal delivery of the TLR3 agonist polyinosinic:polycytidylic acid [poly(I:C)], a synthetic dsRNA structurally similar to virus dsRNA, stimulated IFN-I production and significantly protected against Rhinovirus and Influenza virus infections in humans (10). This immune prophylaxis was safe and well tolerated.…”

Section: Introductionmentioning

confidence: 99%

A novel Pan-viral prophylaxis strategy using vaccine adjuvant CAF09b protects against influenza virus infection

Zimmermann

Schmidt

Trebbien

et al. 2021

Preprint

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The SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I related gene expression. When CAF09b was administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although virus was still detectable in the lungs. However, when CAF09b was administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.

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PrEP-001 prophylactic effect against rhinovirus and influenza virus - RESULTS of 2 randomized trials

Abstract: Study 1, HRV-A16 study: EudraCT Number 2012-005579-14 (study conducted before ClinicalTrials.gov registration required). Study 2, H3N2-IAV study: EudraCT Number 2015-002895-26 and ClinicalTrials.gov: NCT03220048.

Cited by 8 publications

References 32 publications

Prevention and treatment of HIV infection and cognitive disease in mice by innate immune responses

Prevention and treatment of HIV infection and cognitive disease in mice by innate immune responses

A Novel Prophylaxis Strategy Using Liposomal Vaccine Adjuvant CAF09b Protects against Influenza Virus Disease

A novel Pan-viral prophylaxis strategy using vaccine adjuvant CAF09b protects against influenza virus infection

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