mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials

Feldman, Robert; Fuhr, Rainard; Smolenov, Igor; Ribeiro, Amilcar Mick; Panther, Lori; Watson, Michael; Senn, Joseph J.; Smith, Matthew F.; Almarsson, Ӧrn; Pujar, Hari; Laska, Michael E.; Thompson, James D.; Zaks, Tal; Ciaramella, Giuseppe

doi:10.1016/j.vaccine.2019.04.074

Cited by 353 publications

(264 citation statements)

References 29 publications

Supporting

Mentioning

256

Contrasting

Unclassified

Order By: Relevance

“…The mRNA delivery field is still relatively new and there have only been a few mRNA gene therapy clinical trials and even fewer for delivery of antigens as vaccines or for in vivo encoded antibody delivery. The few mRNA studies reported have described primarily mild-to-moderate injections site reactions [55,71]; however, these can have a high frequency, and occasionally they have been serious. In a small vaccination study, a serious adverse event was reported following administration of an mRNA-rabies vaccine [55].…”

Section: Safety and Integrationmentioning

confidence: 99%

In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies

2020

View full text Add to dashboard Cite

Antibody immunotherapy is revolutionizing modern medicine. The field has advanced dramatically over the past 40 years, driven in part by major advances in isolation and manufacturing technologies that have brought these important biologics to the forefront of modern medicine. However, the global uptake of monoclonal antibody (mAb) biologics is impeded by biophysical and biochemical liabilities, production limitations, the need for cold-chain storage and transport, as well as high costs of manufacturing and distribution. Some of these hurdles may be overcome through transient in vivo gene delivery platforms, such as non-viral synthetic plasmid DNA and messenger RNA vectors that are engineered to encode optimized mAb genes. These approaches turn the body into a biological factory for antibody production, eliminating many of the steps involved in bioprocesses and providing several other significant advantages, and differ from traditional gene therapy (permanent delivery) approaches. In this review, we focus on nucleic acid delivery of antibody employing synthetic plasmid DNA vector platforms, and RNA delivery, these being important approaches that are advancing simple, rapid, in vivo expression and having an impact in animal models of infectious diseases and cancer, among others. Key PointsDirect in vivo delivery of synthetic nucleic acidencoded antibodies employing plasmid DNA [plasmid DNA-encoded monoclonal antibodies (pDNA-mAbs)] and messenger RNA-encoded monoclonal antibodies (mRNA-mAbs) platforms represent new approaches for the in vivo delivery of antibody-like biologics.While there are more preclinical data using pDNA-mAbs, both platforms have made significant progress and are demonstrating promising efficacy in infectious disease and cancer studies in small and large animal models.These platforms have advantages such as rapid product development and simpler manufacturing processes, yet they represent different strategies for deployment, with unique advantages and challenges.

show abstract

Section: Safety and Integrationmentioning

confidence: 99%

In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies

2020

View full text Add to dashboard Cite

show abstract

“…In ferrets (ID, 2 × 50/100 mcg), nonhuman primates (ID/IM, 2 × 400 mcg), and humans (IM, 2 × 100 mcg), an H10N8-derived HA mRNA vaccine formulated with LNP elicited HAI titers in the range of 2000-8000, 10,000, and 70, respectively. 62,63 Whether this lack of translation is a function of mRNA not having optimized quality attributes, suboptimal delivery or an inherent limitation of preclinical or in vitro translational models is not known. Understanding this is going to be key for further development.…”

Section: Biotech and Industrial Perspectivesmentioning

confidence: 99%

“…Humoral elicited responses have been generally underwhelming, compared with the established potency in the field of protein or live attenuated vaccines. 63,69 This indicates that much formulation work is still needed to achieve sufficient immunological potency of different vaccine candidates, while maintaining acceptable tolerability-but we can be encouraged by incremental progress to date. Furthermore, very limited data exist on repeat administration of mRNA vaccines in humans.…”

Section: Biotech and Industrial Perspectivesmentioning

confidence: 99%

The promise of mRNA vaccines: a biotech and industrial perspective

Jackson¹,

et al. 2020

View full text Add to dashboard Cite

mRNA technologies have the potential to transform areas of medicine, including the prophylaxis of infectious diseases. The advantages for vaccines range from the acceleration of immunogen discovery to rapid response and multiple disease target manufacturing. A greater understanding of quality attributes that dictate translation efficiency, as well as a comprehensive appreciation of the importance of mRNA delivery, are influencing a new era of investment in development activities. The application of translational sciences and growing early-phase clinical experience continue to inform candidate vaccine selection.Here we review the state of the art for the prevention of infectious diseases by using mRNA and pertinent topics to the biotechnology and pharmaceutical industries.npj Vaccines (2020) 5:11 ; https://doi.

show abstract

“…Third, a vaccine against COVID-19 using the mRNA antigens technology protocol will be available several years from now. Only recently, has there been a phase 1 clinical trials for mRNA vaccines against H10N8 and H7N9 Influenza viruses [13] and the research work for HIV-1 is still at its infancy [14]. It must be noted that there has not been any clinical trials for mRNA vaccines targeting SARS-COV since the 2002-2004 SARS outbreak [15].…”

Section: According To the World Health Organization's Director (Who)mentioning

confidence: 99%

In The Matter Of The Virus That Causes Corona Virus Disease (COVID-19), SARS-COV-2: A Case Predicted By The Theory Of Chaos

Tung

2020

Preprint

View full text Add to dashboard Cite

The current Corona Virus Disease (COVID-19) pandemic that is caused by the virus termed SARS-COV-2, started from an apparently innocuous isolated incident in an unknown place and time. However, in a very short time, the matter of COVID-19 has become a world-wide pandemic, affecting the well-being of billions of individuals, causing hundreds of thousands of severe illnesses, thousands of death (still counting and projected to increase dramatically), unnecessary strains on the world's economy (perhaps triggering another world economic recession if not an economic depression like the ones we have never seen), and most importantly needless fear and distrust in the ability of the leadership to deal with it. The matter of COVID-19 and SARS-COV-2 is a case that was predictable pursuant to the "Theory of Chaos". It is submitted that because the leadership of United States National Institutes of Health, the National Institutes of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention are guilty of dereliction of duties, they must voluntarily resign from their positions that they have occupied for far too long, and that it is high time that the United States Government drastically rethink its policy of the management of this country's biomedical research enterprise that each year pours over 50 billion dollars (all Agencies included) of the people's hard earned tax dollars into a black hole of scientific data that are not only useless but cannot be reproduced by other Scientific Researchers and by the "Scientific Researchers" who generated the "scientific data" in the first place. It is also submitted that had the leadership of United States National Institutes of Health, the National Institutes of Allergy and Infectious Diseases and the Centers for Disease Control and Prevention read and studied the "Theory of Chaos" and the "Art of War", America would not be in the situation it is currently facing.

show abstract

mRNA vaccines against H10N8 and H7N9 influenza viruses of pandemic potential are immunogenic and well tolerated in healthy adults in phase 1 randomized clinical trials

Cited by 353 publications

References 29 publications

In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies

In Vivo Delivery of Nucleic Acid-Encoded Monoclonal Antibodies

The promise of mRNA vaccines: a biotech and industrial perspective

In The Matter Of The Virus That Causes Corona Virus Disease (COVID-19), SARS-COV-2: A Case Predicted By The Theory Of Chaos

Contact Info

Product

Resources

About