V451 vaccine

Last updated
V451 vaccine
Vaccine description
Target SARS-CoV-2
Vaccine type Protein subunit
Clinical data
Other namesSARS-CoV-2 Sclamp
Routes of
administration
Intramuscular
Legal status
Legal status
  • Terminated

V451 was a COVID-19 vaccine candidate developed by the University of Queensland and the Australian pharmaceutical company CSL Limited. The vaccine candidate used the University of Queensland's molecular clamp technology [1] and the MF59 adjuvant. [2]

Contents

Description

V451 is a protein subunit vaccine. As part of the vaccine's design, researchers added "a fragment of one protein found on the HIV virus" [3] as a "ground-breaking molecular clamp technology". [4]

Terminated trial

The development of the vaccine was cancelled on 11 December 2020 during its Phase I trial, after a number of trial participants were found to give false positive test results for HIV antibodies when they did not in fact have HIV. [5] [6] This was due to the HIV virus fragment used as a molecular clamp leading to "a partial antibody response" to HIV. This is an undesirable outcome as it will interfere with future HIV screening tests for affected participants. [7]

Nine days prior to the termination, on 2 December, the first emergency use authorisation had been granted to a COVID-19 vaccine; the Pfizer–BioNTech COVID-19 vaccine in the United Kingdom. [8] Following the termination of V451, vaccine production capacity by CSL Limited was diverted to the Oxford–AstraZeneca COVID-19 vaccine. [9]

Related Research Articles

HIV vaccine development In-progress vaccinations that may prevent or treat HIV infections

An HIV vaccine could be either a preventive vaccine or a therapeutic vaccine, which means it will either protect individuals from being infected with HIV or treat HIV-infected individuals. It could either induce an immune response against HIV or consist of preformed antibodies against HIV.

<i>Adenoviridae</i> Family of viruses

Adenoviruses are medium-sized, nonenveloped viruses with an icosahedral nucleocapsid containing a double stranded DNA genome. Their name derives from their initial isolation from human adenoids in 1953.

In immunology, seroconversion is the development of specific antibodies in the blood serum as a result of infection or immunization. After seroconversion has occurred, the antibodies can be detected in blood tests for the disease. During an infection or immunization, antigens enter the blood, and the immune system begins to produce antibodies in response. Before seroconversion, the antigen itself may or may not be detectable, but the antibody is, by definition, absent. During seroconversion, the antibody is present but not yet detectable.

CSL Limited Australian biotechnology company

CSL Limited is an Australian multinational specialty biotechnology company that researches, develops, manufactures, and markets products to treat and prevent serious human medical conditions. CSL's product areas include blood plasma derivatives, vaccines, antivenom, and cell culture reagents used in various medical and genetic research and manufacturing applications.

Antibody-dependent enhancement A way in which antibodies can (rarely) make an infection worse instead of better

Antibody-dependent enhancement (ADE), sometimes less precisely called immune enhancement or disease enhancement, is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells, followed by its replication. The suboptimal antibodies can result from natural infection or from vaccination. ADE may cause enhanced respiratory disease and acute lung injury after respiratory virus infection (ERD) with symptoms of monocytic infiltration and an excess of eosinophils in respiratory tract. ADE along with type 2 T helper cell-dependent mechanisms may contribute to a development of the vaccine associated disease enhancement (VADE), which is not limited to respiratory disease. Some vaccine candidates that targeted coronaviruses, RSV virus and Dengue virus elicited VADE, and were terminated from further development or became approved for use only for patients who had those viruses before.

GeoVax is a clinical-stage biotechnology company initially established primarily to develop an effective and safe vaccine against many serious human diseases for which there are significant unmet medical needs. GeoVax’ novel development platform builds on the proven clinical and commercial success of the Modified Vaccinia Ankara (MVA) vector technology, with improvements to antigen design and manufacturing capabilities. GeoVax technology approach uses recombinant DNA or recombinant viruses to produce virus-like particles (VLPs) in the person being vaccinated. In human clinical trials of the company’s HIV vaccines, GeoVax demonstrated that VLPs are safe and eliciting both strong and durable humoral and cellular immune response.

MVA-B, or Modified Vaccinia Ankara B, is a HIV vaccine created to give immune resistance to infection by the human immunodeficiency virus. It was developed by a team of Spanish researchers at the Spanish National Research Council's Biotechnology National Centre headed by Dr. Mariano Esteban. The vaccine is based on the Modified vaccinia Ankara (MVA) virus used during the 1970s to help eradicate the smallpox virus. The B in the name "refers to HIV-B, the most common HIV subtype in Europe". It has been stated by Dr. Esteban that, in the future, the vaccine could potentially reduce the virulence of HIV to a "minor chronic infection akin to herpes".

Dan Barouch is an American physician, immunologist, and virologist. He is known for his work on the pathogenesis and immunology of viral infections and the development of vaccine strategies for global infectious diseases.

A molecular clamp is a polypeptide used to maintain the shape of proteins in some experimental vaccines. On a virus, pre-fusion proteins on their surface provide an attractive target for an immune reaction. However, if these proteins are removed or made by recombinant technology, they lose their shape and form what is called a "post-fusion form". When part of a virus, these proteins maintain their form by forming a quaternary structure with other viral proteins. The pre-fusion state of the protein is a higher energy metastable state. The extra energy is used to overcome the activation barrier of the fusion to the cell membrane. The virus protein in combination with the clamp polypeptide is called a chimeric polypeptide.

COVID-19 vaccine Vaccine designed to provide acquired immunity against SARS-CoV-2

A COVID‑19 vaccine is a vaccine intended to provide acquired immunity against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2), the virus that causes coronavirus disease 2019 (COVID‑19). Prior to the COVID‑19 pandemic, an established body of knowledge existed about the structure and function of coronaviruses causing diseases like severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). This knowledge accelerated the development of various vaccine platforms during early 2020. The initial focus of SARS-CoV-2 vaccines was on preventing symptomatic, often severe illness. On 10 January 2020, the SARS-CoV-2 genetic sequence data was shared through GISAID, and by 19 March, the global pharmaceutical industry announced a major commitment to address COVID-19. The COVID‑19 vaccines are widely credited for their role in reducing the spread, severity, and death caused by COVID-19.

COVID-19 drug development Preventative and therapeutic medications for COVID-19 infection

COVID-19 drug development is the research process to develop preventative therapeutic prescription drugs that would alleviate the severity of coronavirus disease 2019 (COVID-19). From early 2020 through 2021, several hundred drug companies, biotechnology firms, university research groups, and health organizations were developing therapeutic candidates for COVID-19 disease in various stages of preclinical or clinical research, with 419 potential COVID-19 drugs in clinical trials, as of April 2021.

Marylyn Martina Addo is a German virologist who is a Professor and the German Center for Infection Research (DZIF) Head of Infectious Disease at the University Medical Center Hamburg-Eppendorf. Addo has developed and tested vaccinations that protect people from Ebola virus disease and the MERS coronavirus EMC/2012. She is currently developing a viral vector based COVID-19 vaccine.

Jason S. McLellan is a structural biologist, associate professor in the Department of Molecular Biosciences and Robert A. Welch Chair in Chemistry at The University of Texas at Austin who specializes in understanding the structure and function of viral proteins, including those of coronaviruses. His research focuses on applying structural information to the rational design of vaccines and other therapies for viruses, including SARS-CoV-2, the novel coronavirus that causes COVID-19. McLellan and his team collaborated with researchers at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center to design a stabilized version of the SARS-CoV-2 spike protein, which biotechnology company Moderna used as the basis for the vaccine mRNA-1273, the first COVID-19 vaccine candidate to enter phase I clinical trials in the U.S. At least three other vaccines use this modified spike protein: those from Pfizer and BioNTech; Johnson & Johnson and Janssen Pharmaceutica; and Novavax.

ZF2001 Vaccine against COVID-19

ZF2001, trade-named ZIFIVAX or ZF-UZ-VAC-2001, is an adjuvanted protein subunit COVID-19 vaccine developed by Anhui Zhifei Longcom in collaboration with the Institute of Microbiology at the Chinese Academy of Sciences. The vaccine candidate is in Phase III trials with 29,000 participants in China, Ecuador, Malaysia, Pakistan, and Uzbekistan.

CoVLP COVID-19 vaccine candidate produced in a plant

CoVLP is a COVID-19 vaccine candidate developed by Medicago and GlaxoSmithKline (GSK). It is a coronavirus virus-like particle vaccine grown in the Australian weed, Nicotiana benthamiana.

EpiVacCorona EpiVacCorona vaccine against COVID-19

EpiVacCorona is a peptide-based vaccine against COVID-19 developed by the VECTOR center of Virology. It 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. The third phase of a clinical trial, which should show whether the vaccine is able to protect people from COVID-19 or not, was launched in November 2020 with more than three thousand participants. The interim results of the Phase III study are expected to be announced in late 2021 or early 2022. According to the vaccine developers, the peptides and the viral part of the chimeric protein should immunize people who received this vaccine against SARS-CoV-2 and trigger the production of protective antibodies. However, some experts in the field have expressed concerns about the selection of peptides for use as vaccine antigens. In addition, there are also serious concerns about the vaccine immunogenicity data, which have fueled independent civic research efforts and criticism by some experts. Meanwhile, the EpiVacCorona has received vaccine emergency authorization in a form of government registration in Russia and is available for vaccination outside the clinical trials. The vaccine delivered via intramuscular route and aluminum hydroxide serves as an immunological adjuvant.

SCB-2019 Vaccine candidate against COVID-19

SCB-2019 is a protein subunit COVID-19 vaccine candidate developed by Clover Biopharmaceuticals using an adjuvant from Dynavax technologies. Positive results of Phase I trials for the vaccine were published in The Lancet and the vaccine completed enrollment in its Phase II/III trials in July 2021, with efficacy results expected to be announced by Q3 2021. SCB-2019 is being funded by CEPI as part of COVAX and has received advanced purchase orders from GAVI for 400 million doses.

Sanofi–GSK COVID-19 vaccine Vaccine candidate against COVID-19

The Sanofi–GSK COVID-19 vaccine code-named VAT00002 and VAT00008 is a COVID-19 vaccine candidate developed by Sanofi Pasteur and GSK.

COVAX-19 Vaccine candidate against COVID-19

COVAX-19 is a recombinant protein-based COVID-19 vaccine candidate developed by South Australian based biotech company, Vaxine. It is under clinical trial in collaboration with the Iranian company CinnaGen.

COVID-19 vaccine clinical research

COVID-19 vaccine clinical research is the clinical research on COVID-19 vaccines, including their efficacy, effectiveness and safety. There are 22 vaccines authorized for use by national governments, with six vaccines being approved for emergency or full use by at least one WHO-recognised stringent regulatory authority; and five of them are in Phase IV. 204 vaccines under clinical trials that have not yet been authorized. There are also nine clinical trials on heterologous vaccination courses.

References

  1. "UQ-CSL V451 Vaccine". www.precisionvaccinations.com. Archived from the original on 2020-12-19. Retrieved 2020-12-11.
  2. Meneguzzi J (13 November 2020). "Why a COVID-19 vaccine could further imperil deep-sea sharks". National Geographic.
  3. Slezak, Michael (11 December 2020). "How the UQ coronavirus vaccine induced false-positive HIV test results and why scientists were prepared". ABC News.
  4. Smyth J (11 December 2020). "Australia abandons local Covid vaccine over HIV test concerns". Financial Times.(subscription required)
  5. "Covid: Australian vaccine abandoned over false HIV response". BBC News. 2020-12-11. Retrieved 2020-12-11.
  6. Reuters Staff (2020-12-10). "BRIEF-CSL Says Will Not Progress UQ-CSL V451 COVID-19 Vaccine Candidate To Phase 2/3 Clinical Trials". Reuters. Retrieved 2020-12-11.
  7. "Australia ends local COVID vaccine trials due to HIV false positives". Deutsche Welle. 11 December 2020.
  8. "UK medicines regulator gives approval for first UK COVID-19 vaccine". Medicines and Healthcare products Regulatory Agency (MHRA). 2 December 2020. Archived from the original on 2 December 2020. Retrieved 2 December 2020.
  9. "COVID-19 Update". www.csl.com. Retrieved 2021-01-31.