Hulpstoffen in het SARS-CoV-2 Vaccin


The SARS-CoV-2, a member of family Coronaviridae and the causative agent of COVID-19 disease, has spread rapidly around the globe since the first outbreak in Wuhan, China in December 2019. The World Health Organization (WHO) declared the outbreak as the sixth public health emergency of international concern on 30th January 2020. Despite the tremendous efforts to contain the virus, its spread is ongoing. Though the majority of cases resolve spontaneously, some develop various fatal complications, including organ failure, septic shock, pulmonary edema, severe pneumonia, and Acute Respiratory Distress Syndrome (ARDS). Before the current pandemic, highly pathogenic CoVs have hit the world as severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003 and Middle East Respiratory Syndrome (MERS) coronavirus in 2012. The SARS-CoV-2 has been identified as a coronavirus, and like SARS-CoV, it binds to angiotensin converting enzyme 2 (ACE2) receptors.

Review Article in Nature Partner Journals Vaccines: 11, 1 – 6, 2020
Nicholas A. C. Jackson1, Kent E. Kester, Danilo Casimiro, Sanjay Gurunathan and Frank DeRosa
The promise of mRNA vaccines – a biotech and industrial perspective

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. However, these early claims need further confirmation, and in many cases, complete datasets are still awaited. As mentioned above, multi-antigen approaches will only complicate the issue of establishing acceptable tolerability.

Review: ACS Nano: 14, 12522 – 12537, 2020
Young Hun Chung, Veronique Beiss, Steven N. Fiering, and Nicole F. Steinmetz
COVID-19 Vaccine Frontrunners and Their Nanotechnology Design

As of 11 August 2020, 28 of these companies have advanced into clinical trials with Moderna, CanSino, the University of Oxford, BioNTech, Sinovac, Sinopharm, Anhui Zhifei Longcom, Inovio, Novavax, Vaxine, Zydus Cadila, Institute of Medical Biology, and the Gamaleya Research Institute having moved beyond their initial safety and immunogenicity studies. This review analyzes these frontrunners in the vaccine development space and delves into their posted results while highlighting the role of the nanotechnologies applied by all the vaccine developers.

International Immunopharmacology: Vol.86, 106717, 2020
Tania Gupta and Shishir K Gupta
Potential adjuvants for the development of a SARS-CoV-2 vaccine based on experimental results from similar coronaviruses

This review paper will discuss the experimental results of the adjuvanted vaccine studies with similar coronaviruses (CoVs) which might be useful to select an appropriate adjuvant for a vaccine against rapidly emerging SARS-CoV-2. We also discuss the current progress in the development of adjuvanted vaccines against the disease.

Nat Rev Immunol: 20(6), 347-348, 2020
Peter J. Hotez, David B. Corry and Maria Elena Bottazzi
COVID-19 vaccine design – the Janus face of immune enhancement

Previous work on severe acute respiratory syndrome coronavirus (SARS-CoV) vaccines identified cellular immunopathology and antibody-dependent enhancement as potential safety issues. We discuss the implications of these findings for COVID-19 vaccine development and our approach to optimizing for safety and efficacy.

Acta Pharmaceutica Sinica B: 10(7), 1175-1191, 2020
Chunting He, Ming Qin, Xun Sun
Highly pathogenic coronaviruses thrusting vaccine development in the spotlight

To date, there is no specific treatment proven effective against these viral infectious diseases. Vaccination is considered one of the most effective strategies to prevent viral infections. Therefore, the development of effective vaccines against highly pathogenic coronaviruses is essential. In this review, we will briefly describe coronavirus vaccine design targets, summarize recent advances in the development of coronavirus vaccines, and highlight current adjuvants for improving the efficacy of coronavirus vaccines.

The Conservation 14 may 2020, 1 – 4: What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19?
Krishna Sriram, Paul Insel en Rohit Loomba
What is the ACE2 receptor, how is it connected to coronavirus and why might it be key to treating COVID-19? The experts explain

ACE2 is present in many cell types and tissues including the lungs, heart, blood vessels, kidneys, liver and gastrointestinal tract. It is present in epithelial cells, which line certain tissues and create protective barriers. ACE2 is a vital element in a biochemical pathway that is critical to regulating processes such as blood pressure, wound healing and inflammation, called the renin-angiotensin-aldosterone system (RAAS) pathway.

MF59 is Squalene + Tween 80 + Span 85

The adjuvant MF59 is a submicron oil-in-water emulsion composed of 5% v/v squalene, 0.5% v/v Tween 80 and 0.5% v/v Span 85.

CLINICAL AND VACCINE IMMUNOLOGY: Vol. 13-9, 1010–1013, 2006
Giuseppe Del Giudice, Elena Fragapane, Roberto Bugarini, Maninder Hora, Thomas Henriksson, Emanuela Palla, Derek O’Hagan, John Donnelly, Rino Rappuoli and Audino Podda
Vaccines with the MF59 Adjuvant Do Not Stimulate Antibody Responses against Squalene

Squalene is a naturally occurring oil which has been used in the development of vaccine adjuvants, such as the oil-in-water emulsion MF59. In past years, by use of noncontrolled and nonvalidated assays, a claim was made that antisqualene antibodies were detectable in the sera of individuals with the so-called Gulf War syndrome. Using a validated enzyme-linked immunosorbent assay for the quantitation of immunoglobulin G (IgG) and IgM antibodies against squalene, we demonstrated that antisqualene antibodies are frequently detectable at very low titers in the sera of subjects who were never immunized with vaccines containing squalene. More importantly, vaccination with a subunit influenza vaccine with the MF59 adjuvant neither induced antisqualene antibodies nor enhanced preexisting antisqualene antibody titers. In conclusion, anti- squalene antibodies are not increased by immunization with vaccines with the MF59 adjuvant. These data extend the safety profile of the MF59 emulsion adjuvant.

Effect aluminium in vaccins

Aluminum hydroxide, Aluminum phosphate and Aluminum potassium sulfate dodecahydrate

Environmental Toxicology and Pharmacology: 78, 103404, 2020
Isaac Niesa, Krisha Hidalgoa, Stephen C. Bondyb en Arezoo Campbell
Distinctive cellular response to aluminum based adjuvants

Aluminum-based adjuvants (ABAs) are used in human vaccines to enhance the magnitude of protective immune responses elicited against specific pathogens. One hypothesis is that stress signals released by aluminum-exposed necrotic cells play a role in modulating an immune response that contributes to the adjuvant’s effectiveness. We hypothesized that aluminum adjuvant-induced necrosis would be similar irrespective of cellular origin or composition of the adjuvant. To test this hypothesis, human macrophages derived from peripheral monocytic cell line (THP-1) and cells derived from the human brain (primary astrocytes) were evaluated. Three com- mercially available formulations of ABAs (Alhydrogel, Imject alum, and Adju-Phos) were examined.

After exposure to ABAs, astrocytes and macrophages presented a distinct profile of cytokine secretion which may relate to the function and unique characteristics of each cell type. These variations indicate that aluminum adjuvants may have differing capability of activating cells of different origin and thus their utility in specific vaccine design should be carefully assessed for optimum efficacy.

Effect formaldehyde in vaccins

Formaldehyde wordt gebruikt om bacteriën en virussen te inactiveren, alvorens het in vaccins te gebruiken. Formaldehyde is hormoonverstorend en benadeelt de kwaliteit van het veldcontact. Daarom kan het lipofiele formaldehyde vanaf de eerste vaccinatie – vaak al op de leeftijd van een paar maanden – de verdere ontwikkeling van de baby benadelen. En juist tijdens de eerste twee jaren van het jonge leven – wanneer de hersenontwikkeling eigenlijk nog een voortzetting is van de eerste prenatale ontwikkelingsperiode – zijn verzwakking van de kwaliteit van het veldcontact en hormoonverstorende invloeden zeer gevaarlijk en kunnen daardoor makkelijk stoornissen ontstaan zoals autisme, ADHD, de aanleg voor schizofrenie en de borderline-stoornis en allerlei mengvormen hiervan die met elkaar overlappen en vaak vallen onder het autistisch spectrum.

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