Rapid Deployment Vaccine Collaborative

Last updated
Rapid Deployment Vaccine Collaborative
AbbreviationRaDVaC
FormationMarch 2020
Type 501(c)(3) organization
PurposeTo design, produce, test, and share open-source vaccine research in an effort to accelerate and strengthen COVID-19 vaccine development
Key people
Preston Estep, Alexander Hoekstra, Don Wang, Ranjan Ahuja, Brian M. Delaney, George Church
Website radvac.org

The Rapid Deployment Vaccine Collaborative (RaDVaC), is a non-profit, collaborative, open-source vaccine research organization founded in March 2020 by Preston Estep and colleagues from various fields of expertise, motivated to respond to the COVID-19 pandemic through rapid, adaptable, transparent, and accessible vaccine development. [1] [2] [3] [4] [5] [6] [7] [8] [9] The members of RaDVaC contend that even the accelerated vaccine approvals, such as the FDA's Emergency Use Authorization, does not make vaccines available quickly enough. [10] The core group has published a series of white papers online, [11] detailing both the technical principles of and protocols for their research vaccine formulas, as well as dedicated materials [12] and protocols [13] pages. All of the organization's published work has been released under Creative Commons non-commercial licenses, including those contributing to the Open COVID Pledge. [14] Multiple individuals involved with the project have engaged in self-experimentation to assess vaccine safety and efficacy. As of January 2022, the organization has developed and published twelve iterations of experimental intranasal, multivalent, multi-epitope peptide vaccine formulas, and according to the RaDVaC website, by early 2021 hundreds of individuals had self-administered one or more doses of the vaccines described by the group.

Contents

History

In March 2020, Preston Estep sent an email to several associates in an effort to determine whether any open-source vaccine projects were underway. Finding none, he and several colleagues formed RaDVaC in the following days, and began constructing the first generation of the RaDVaC research vaccine formula.[ citation needed ]

Self-experimentation

Several of RaDVaC's core members and numerous others have engaged in self-experimentation to assess both the safety and efficacy of the vaccine formulations. Dr. Estep self-administered the first dose on March 30, 2020. As of early 2020, the group claims that hundreds of individuals had self-administered one or more doses of one or more generations of the RaDVaC experimental vaccine. [15] [16]

Open-source and iterative vaccine research and development

RaDVaC considers responsive iteration a key asset in developing vaccines against an emerging disease such as COVID-19. In contrast to commercial vaccine R&D infrastructure, RaDVaC's core group adapted their vaccine designs in response to emerging research on the pathology and immunology of SARS-CoV-2 and COVID-19.[ citation needed ]

SARS-CoV-2 Peptide Vaccines

Early generations (gen. 1-6)

  • Included primarily B cell epitopes, both emergent from computational predictions as well as early research in SARS-CoV-2 antibody mapping.

Generation 7

  • First inclusion of empirical T cell response data.

Generation 8

  • Better characterization of T cell response.

Generation 9

Generation 10 [17]

  • Improved solubility at physiological pH by the use of derivatized chitosan (for example: trimethyl chitosan [TMC] or hydroxypropyltrimethylammonium chloride chitosan [HACC]), instead of unmodified chitosan.
  • Increased T helper activation combined with reduced MHC Class II restriction to more robustly activate cytotoxic T lymphocytes and B cells for antibody production.
  • Surface display of antigens for improved antibody response.
  • A smaller set of core peptides (5 peptides) combined with a list of optional peptides, providing greater functionality and improved representation of common MHC Class I alleles.
  • An optional epitope sequence that includes an increasingly common variant (N501Y) in the Spike Receptor Binding Motif (RBM). The RaDVaC primary protective strategy remains focused on the more highly conserved epitopes involved in membrane fusion, but groups are testing the potential of this epitope sequence to boost the systemic antibody response.
  • An optional dendritic cell targeting peptide for delivering T cell epitopes to dendritic cells, an important cell type in the presentation of T cell antigens.

Generation 11 [18]

  • The only difference between Generation 10 and Generation 11 vaccine designs is the addition to Gen. 11 of the peptide MVC2-s, which represents the Receptor Binding Domain (RBD)/Receptor Binding Motif (RBM), and has 2 mutations that are present in variants of concern and interest: the L452R mutation found in Delta, Iota, and Kappa, and the N501Y mutation found in Alpha, Beta, Gamma and Mu.

Generation 12 [19]

  • The Generation 12 vaccine design is very similar to Generation 11, but with one major change and some minor ones. The major change is the addition of the Omicron-specific SARS-CoV-2 Receptor Binding Motif peptide ("RBMO-sc") to the set of core peptides, and the subtraction of "MVC1-s" from the set of optional peptides. Certain T cell epitope peptides were also changed. "Orf1ab 5528T" replaced "Orf1 1636T" in the list of core peptides, because the former is bound by all of the Class I receptors that bind "Orf1 1636T" but it also binds several others. RaDVaC also eliminated "Nuc 264T-key" from the list of optional peptides because the homologous sequence in SARS-CoV-1 reportedly suppresses cytokine signaling. [20]

Open-source clinical trial design

In April 2022, RaDVaC published a proposal for a novel vaccine clinical trial design, called a "step-up challenge trial". [21] The proposed model is intended to validate immuno-efficacy of broad-spectrum vaccines, including pan-coronavirus vaccines, but subjecting ("challenging") study participants to multiple related pathogens with different degrees of pathogenicity.[ citation needed ]

Funding and awards

In December 2021 ACX Grants announced that RaDVaC had been awarded US$100,000 "to make open-source modular affordable vaccines." [22] In May 2022 RaDVaC tweeted it had been awarded US$2.5 million from Balvi, [23] a moonshot anti-covid effort established by Vitalik Buterin. [24]

Related Research Articles

<span class="mw-page-title-main">Antigen</span> Molecule triggering an immune response (antibody production) in the host

In immunology, an antigen (Ag) is a molecule, moiety, foreign particulate matter, or an allergen, such as pollen, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.

An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that binds to the epitope is called a paratope. Although epitopes are usually non-self proteins, sequences derived from the host that can be recognized are also epitopes.

<span class="mw-page-title-main">Original antigenic sin</span> Immune phenomenon

Original antigenic sin, also known as antigenic imprinting, the Hoskins effect, immunological imprinting, or primary addiction is the propensity of the immune system to preferentially use immunological memory based on a previous infection when a second slightly different version of that foreign pathogen is encountered. This leaves the immune system "trapped" by the first response it has made to each antigen, and unable to mount potentially more effective responses during subsequent infections. Antibodies or T-cells induced during infections with the first variant of the pathogen are subject to repertoire freeze, a form of original antigenic sin.

<span class="mw-page-title-main">Epitope mapping</span> Identifying the binding site of an antibody on its target antigen

In immunology, epitope mapping is the process of experimentally identifying the binding site, or epitope, of an antibody on its target antigen. Identification and characterization of antibody binding sites aid in the discovery and development of new therapeutics, vaccines, and diagnostics. Epitope characterization can also help elucidate the binding mechanism of an antibody and can strengthen intellectual property (patent) protection. Experimental epitope mapping data can be incorporated into robust algorithms to facilitate in silico prediction of B-cell epitopes based on sequence and/or structural data.

<span class="mw-page-title-main">Linear epitope</span> Segment of a molecule which antibodies recognize by its linear structure

In immunology, a linear epitope is an epitope—a binding site on an antigen—that is recognized by antibodies by its linear sequence of amino acids. In contrast, most antibodies recognize a conformational epitope that has a specific three-dimensional shape.

Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted:

A breakthrough infection is a case of illness in which a vaccinated individual becomes infected with the illness, because the vaccine has failed to provide complete immunity against the pathogen. Breakthrough infections have been identified in individuals immunized against a variety of diseases including mumps, varicella (Chickenpox), influenza, and COVID-19. The characteristics of the breakthrough infection are dependent on the virus itself. Often, infection of the vaccinated individual results in milder symptoms and shorter duration than if the infection were contracted naturally.

<span class="mw-page-title-main">Preston Estep</span> Biogerontologist

Preston "Pete" Wayne Estep III is an American biologist and science and technology advocate. He is a graduate of Cornell University, where he did neuroscience research, and he earned a Ph.D. in Genetics from Harvard University. He did his doctoral research in the laboratory of genomics pioneer Professor George M. Church at Harvard Medical School.

<span class="mw-page-title-main">La Jolla Institute for Immunology</span> Research institute near San Diego, California, U.S.

La Jolla Institute for Immunology is a non-profit research organization located in La Jolla, San Diego, California. It is located in UC San Diego’s Research Park. The institute researches immunology and immune system diseases. The institute employs 220 M.D.s and Ph.D.s, including 23 faculty members and more than 450 employees. Dr. Mitchell Kronenberg has served as its president and scientific director since 2003. The institute was founded in 1988.

A subunit vaccine is a vaccine that contains purified parts of the pathogen that are antigenic, or necessary to elicit a protective immune response. Subunit vaccine can be made from dissembled viral particles in cell culture or recombinant DNA expression, in which case it is a recombinant subunit vaccine.

Peptide-based synthetic vaccines are subunit vaccines made from peptides. The peptides mimic the epitopes of the antigen that triggers direct or potent immune responses. Peptide vaccines can not only induce protection against infectious pathogens and non-infectious diseases but also be utilized as therapeutic cancer vaccines, where peptides from tumor-associated antigens are used to induce an effective anti-tumor T-cell response.

Immunomics is the study of immune system regulation and response to pathogens using genome-wide approaches. With the rise of genomic and proteomic technologies, scientists have been able to visualize biological networks and infer interrelationships between genes and/or proteins; recently, these technologies have been used to help better understand how the immune system functions and how it is regulated. Two thirds of the genome is active in one or more immune cell types and less than 1% of genes are uniquely expressed in a given type of cell. Therefore, it is critical that the expression patterns of these immune cell types be deciphered in the context of a network, and not as an individual, so that their roles be correctly characterized and related to one another. Defects of the immune system such as autoimmune diseases, immunodeficiency, and malignancies can benefit from genomic insights on pathological processes. For example, analyzing the systematic variation of gene expression can relate these patterns with specific diseases and gene networks important for immune functions.

Immunodominance is the immunological phenomenon in which immune responses are mounted against only a few of the antigenic peptides out of the many produced. That is, despite multiple allelic variations of MHC molecules and multiple peptides presented on antigen presenting cells, the immune response is skewed to only specific combinations of the two. Immunodominance is evident for both antibody-mediated immunity and cell-mediated immunity. Epitopes that are not targeted or targeted to a lower degree during an immune response are known as subdominant epitopes. The impact of immunodominance is immunodomination, where immunodominant epitopes will curtail immune responses against non-dominant epitopes. Antigen-presenting cells such as dendritic cells, can have up to six different types of MHC molecules for antigen presentation. There is a potential for generation of hundreds to thousands of different peptides from the proteins of pathogens. Yet, the effector cell population that is reactive against the pathogen is dominated by cells that recognize only a certain class of MHC bound to only certain pathogen-derived peptides presented by that MHC class. Antigens from a particular pathogen can be of variable immunogenicity, with the antigen that stimulates the strongest response being the immunodominant one. The different levels of immunogenicity amongst antigens forms what is known as dominance hierarchy.

<span class="mw-page-title-main">Vitalik Buterin</span> Russian-Canadian programmer (born 1994)

Vitaly Dmitrievich Buterin, better known as Vitalik Buterin, is a Russian-Canadian computer programmer, and co-founder of Ethereum. Buterin became involved with cryptocurrency early in its inception, co-founding Bitcoin Magazine in 2011. In 2014, Buterin deployed the Ethereum blockchain with Gavin Wood, Charles Hoskinson, Anthony Di Iorio, and Joseph Lubin.

<span class="mw-page-title-main">Alessandro Sette</span> Italian immunologist (born 1960)

Alessandro Sette is an Italian immunologist. He was born on August 11, 1960, in Rome, Italy, to Pietro Sette, a prominent Italian businessman and politician, and Renata Sette. Sette is a professor at La Jolla Institute for Immunology (LJI). He is an adjunct professor at the University of California, San Diego. Sette studies the specific epitopes that the immune system recognizes in cancer, autoimmunity, allergy, and infectious diseases.

<span class="mw-page-title-main">EpiVacCorona</span> EpiVacCorona vaccine against COVID-19

EpiVacCorona is a peptide-based vaccine against COVID-19 developed by the Russian VECTOR Center of Virology. The lack of protective effectiveness of EpiVacCorona, which is still in use in Russia, has been reported in scientific literature and in the media. The vaccine consists of three chemically synthesized peptides that are conjugated to a large carrier protein. This protein is a fusion product of a viral nucleocapsid protein and a bacterial MBP protein. A phase III clinical trial to show whether or not the vaccine can protect people against COVID-19 was launched in November 2020 with more than three thousand participants. The conclusions and results of the trial have not been made public.

<span class="mw-page-title-main">UB-612</span> Vaccine candidate against COVID-19

UB-612 is a COVID-19 vaccine candidate developed by United Biomedical Asia, and Vaxxinity, Inc. It is a peptide vaccine.

<span class="mw-page-title-main">Coronavirus spike protein</span> Glycoprotein spike on a viral capsid or viral envelope

Spike (S) glycoprotein is the largest of the four major structural proteins found in coronaviruses. The spike protein assembles into trimers that form large structures, called spikes or peplomers, that project from the surface of the virion. The distinctive appearance of these spikes when visualized using negative stain transmission electron microscopy, "recalling the solar corona", gives the virus family its main name.

<span class="mw-page-title-main">Universal coronavirus vaccine</span> Vaccine that prevents infection from all strains of coronaviruses

A universal coronavirus vaccine, also known as a pan-coronavirus vaccine, is a theoretical coronavirus vaccine that would be effective against all coronavirus strains. A universal vaccine would provide protection against coronavirus strains that have caused disease in humans, such as SARS-CoV-2, while also providing protection against future coronavirus strains. Such a vaccine has been proposed to prevent or mitigate future coronavirus epidemics and pandemics.

<span class="mw-page-title-main">COH04S1</span> Vaccine candidate against COVID-19

COH04S1 is a covid vaccine developed by the City of Hope Medical Center. This vaccine targets patients who are immunocompromised; immunocompromised patients have often shown a weak antibody response to past COVID-19 vaccines. COH04S1 is also targeted on people who are at a high risk of COVID-19 complications. The City of Hope Medical Center strives to make a better option than the current EUA and FDA approved vaccines, which are not working as well on this group of individuals.

References

  1. "'Warp speed' is too slow for scientists testing COVID-19 vaccine on themselves" . Retrieved 2020-12-16.
  2. "US scientists taking home-made Covid vaccines". 16 December 2020. Retrieved 2020-12-27.
  3. "Some scientists taking 'DIY inoculations' instead of waiting for COVID-19 vaccine". 26 September 2020. Retrieved 2020-12-27.
  4. "Do-It-Yourself Vaccines for COVID-19". Scientific American . Retrieved 2020-12-27.
  5. "Opinion: Even in a pandemic, how comfortable would you feel about open-source vaccine?". 9 August 2020. Retrieved 2020-12-27.
  6. "Scientists Have Built A Mix-It-Yourself Vaccine And Taken It Themselves Without FDA Approval". 5 August 2020. Retrieved 2020-12-27.
  7. "Researchers Testing Do-It-Yourself COVID-19 Vaccine on Themselves". 4 August 2020. Retrieved 2020-12-27.
  8. "Scientists Just Released a DIY Coronavirus Vaccine Under a Creative Commons License". 30 July 2020. Retrieved 2020-12-27.
  9. "Some scientists are taking a DIY coronavirus vaccine, and nobody knows if it's legal or if it works" . Retrieved 2020-12-27.
  10. "US scientists taking home-made Covid vaccines". 16 December 2020. Retrieved 2021-03-02.
  11. "White paper – RaDVaC" . Retrieved 2020-09-29.
  12. "Materials and equipment – RaDVaC" . Retrieved 2020-09-29.
  13. "Protocols for making and taking the vaccine – RaDVaC" . Retrieved 2020-09-29.
  14. "Partners". Open Covid Pledge. Retrieved 2020-09-29.
  15. Murphy, Heather (2020-09-08). "These Scientists Are Giving Themselves D.I.Y. Coronavirus Vaccines". The New York Times. ISSN   0362-4331 . Retrieved 2020-09-29.
  16. "Making Vaccine - LessWrong". www.lesswrong.com. Retrieved 2022-04-20.
  17. RaDVaC - SARS-CoV-2 (2019-nCoV) vaccine, Version 4-0-0, March 7, 2021
  18. RaDVaC - SARS-CoV-2 (2019-nCoV) vaccine, Version 4-1-3, September 16, 2021
  19. RaDVaC - SARS-CoV-2 (2019-nCoV) vaccine, Version 5-0-0, January 14, 2022
  20. Lu, Xiaolu; Pan, Ji'an; Tao, Jiali; Guo, Deyin (February 2011). "SARS-CoV nucleocapsid protein antagonizes IFN-β response by targeting initial step of IFN-β induction pathway, and its C-terminal region is critical for the antagonism". Virus Genes. 42 (1): 37–45. doi:10.1007/s11262-010-0544-x. ISSN   1572-994X. PMC   7088804 . PMID   20976535.
  21. "RaDVaC step-up challenge trial: design and rationale, version 1-1-0" (PDF). RaDVaC. April 10, 2022.
  22. Alexander, Scott (2021-12-28). "ACX Grants Results". Astral Codex Ten. Retrieved 2022-07-01.
  23. @RADVACproject (May 3, 2022). "Excited to announce that RaDVaC has been awarded $2.5M USD from Balvi, in order to advance work to close the vaccine access gap. Balvi is a direct giving fund established by @VitalikButerin, for high-impact COVID projects. Full announcement here: http://radvac.org/updates" (Tweet). Archived from the original on 2022-07-02. Retrieved 2022-07-01 via Twitter.
  24. Buterin, Vitalik [@VitalikButerin] (May 5, 2022). "Update from Balvi! (moonshot anti-covid effort funded by @ShibainuCoin @CryptoRelief_ ). We have our first round of funding recipients" (Tweet). Archived from the original on 2022-07-02. Retrieved 2022-07-01 via Twitter.