Posts Tagged ‘vaccine development’

The NIH-funded adjuvant improves the efficacy of India’s COVID-19 vaccine.

Posted in Allergy and Infectious Diseases, CEOs of Biotech Companies, coronavirus, COVID-19, Drug Development Process, Immunology, Infectious Disease Immunodiagnostics, Mechanisms of infection by SARS-CoV-2, SARS-CoV-2, SARS-CoV-2 circulating variants , SARS-CoV-2 Viral Variants, Viral diseases, Virology, tagged Antibodies, COVID Vaccine, COVID-19 SARS-CoV-2, COVID-19 Treatment, infection, National Institute of Allergy and Infectious Diseases (NIAID), NIH, vaccine adjuvant platorm technology, vaccine development on July 2, 2021| Leave a Comment »

The NIH-funded adjuvant improves the efficacy of India’s COVID-19 vaccine.

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Anthony S. Fauci, Director of the National Institute of Allergy and Infectious Diseases (NIAID), Part of National Institute of Health (NIH) said,

Ending a global pandemic demands a global response. I am thrilled that a novel vaccine adjuvant developed in the United States with NIAID support is now included in an effective COVID-19 vaccine that is available to individuals in India.”

**Image Source:**https://www.bharatbiotech.com/

Adjuvants are components that are created as part of a vaccine to improve immune responses and increase the efficiency of the vaccine. COVAXIN was developed and is manufactured in India, which is currently experiencing a terrible health catastrophe as a result of COVID-19. An adjuvant designed with NIH funding has contributed to the success of the extremely effective COVAXIN-COVID-19 vaccine, which has been administered to about 25 million individuals in India and internationally.

Alhydroxiquim-II is the adjuvant utilized in COVAXIN, was discovered and validated in the laboratory by the biotech company ViroVax LLC of Lawrence, Kansas, with funding provided solely by the NIAID Adjuvant Development Program. The adjuvant is formed of a small molecule that is uniquely bonded to Alhydrogel, often known as alum and the most regularly used adjuvant in human vaccines. Alhydroxiquim-II enters lymph nodes, where it detaches from alum and triggers two cellular receptors. TLR7 and TLR8 receptors are essential in the immunological response to viruses. Alhydroxiquim-II is the first adjuvant to activate TLR7 and TLR8 in an approved vaccine against an infectious disease. Additionally, the alum in Alhydroxiquim-II activates the immune system to look for an infiltrating pathogen.

Although molecules that activate TLR receptors strongly stimulate the immune system, the adverse effects of Alhydroxiquim-II are modest. This is due to the fact that after COVAXIN is injected, the adjuvant travels directly to adjacent lymph nodes, which contain white blood cells that are crucial in recognizing pathogens and combating infections. As a result, just a minimal amount of Alhydroxiquim-II is required in each vaccination dosage, and the adjuvant does not circulate throughout the body, avoiding more widespread inflammation and unwanted side effects.

This scanning electron microscope image shows SARS-CoV-2 (round gold particles) emerging from the surface of a cell cultured in the lab. SARS-CoV-2, also known as 2019-nCoV, is the virus that causes COVID-19. Image Source: **NIAID**

COVAXIN is made up of a crippled version of SARS-CoV-2 that cannot replicate but yet encourages the immune system to produce antibodies against the virus. The NIH stated that COVAXIN is “safe and well tolerated,” citing the results of a phase 2 clinical investigation. COVAXIN safety results from a Phase 3 trial with 25,800 participants in India will be released later this year. Meanwhile, unpublished interim data from the Phase 3 trial show that the vaccine is 78% effective against symptomatic sickness, 100% effective against severe COVID-19, including hospitalization, and 70% effective against asymptomatic infection with SARS-CoV-2, the virus that causes COVID-19. Two tests of blood serum from persons who had received COVAXIN suggest that the vaccine creates antibodies that efficiently neutralize the SARS-CoV-2 B.1.1.7 (Alpha) and B.1.617 (Delta) variants (1) and (2), which were originally identified in the United Kingdom and India, respectively.

Since 2009, the NIAID Adjuvant Program has supported the research of ViroVax’s founder and CEO, Sunil David, M.D., Ph.D. His research has focused on the emergence of new compounds that activate innate immune receptors and their application as vaccination adjuvants.

Dr. David’s engagement with Bharat Biotech International Ltd. of Hyderabad, which manufactures COVAXIN, began during a 2019 meeting in India organized by the NIAID Office of Global Research under the auspices of the NIAID’s Indo-US Vaccine Action Program. Five NIAID-funded adjuvant investigators, including Dr. David, two representatives of the NIAID Division of Allergy, Immunology, and Transplantation, and the NIAID India representative, visited 4 top biotechnology companies to learn about their work and discuss future collaborations. The delegation also attended a consultation in New Delhi, which was co-organized by the NIAID and India’s Department of Biotechnology and hosted by the National Institute of Immunology.

Among the scientific collaborations spawned by these endeavors was a licensing deal between Bharat Biotech and Dr. David to use Alhydroxiquim-II in their candidate vaccines. During the COVID-19 outbreak, this license was expanded to cover COVAXIN, which has Emergency Use Authorization in India and more than a dozen additional countries. COVAXIN was developed by Bharat Biotech in partnership with the Indian Council of Medical Research’s National Institute of Virology. The company conducted thorough safety research on Alhydroxiquim-II and undertook the arduous process of scaling up production of the adjuvant in accordance with Good Manufacturing Practice standards. Bharat Biotech aims to generate 700 million doses of COVAXIN by the end of 2021.

NIAID conducts and supports research at the National Institutes of Health, across the United States, and across the world to better understand the causes of infectious and immune-mediated diseases and to develop better methods of preventing, detecting, and treating these illnesses. The NIAID website contains news releases, info sheets, and other NIAID-related materials.

Main Source:

https://www.miragenews.com/adjuvant-developed-with-nih-funding-enhances-587090/

References

Other Related Articles published in this Open Access Online Scientific Journal include the following:

Comparing COVID-19 Vaccine Schedule Combinations, or “Com-COV” – First-of-its-Kind Study will explore the Impact of using eight different Combinations of Doses and Dosing Intervals for Different COVID-19 Vaccines

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/02/08/comparing-covid-19-vaccine-schedule-combinations-or-com-cov-first-of-its-kind-study-will-explore-the-impact-of-using-eight-different-combinations-of-doses-and-dosing-intervals-for-diffe/

Thriving Vaccines and Research: Weizmann Institute Coronavirus Research Development

Reporter:Amandeep Kaur, B.Sc., M.Sc.

https://pharmaceuticalintelligence.com/2021/05/04/thriving-vaccines-and-research-weizmann-coronavirus-research-development/

National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/07/19/national-public-radio-interview-with-dr-anthony-fauci-on-his-optimism-on-a-covid-19-vaccine-by-early-2021/

Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/04/10/cryo-em-disclosed-how-the-d614g-mutation-changes-sars-cov-2-spike-protein-structure/

Updates on the Oxford, AstraZeneca COVID-19 Vaccine

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/06/16/updates-on-the-oxford-astrazeneca-covid-19-vaccine/

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Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure.

Posted in coronavirus, Coronavirus Gene Expression, COVID-19, COVID-19, Drug Development Process, Genetics & Innovations in Treatment, Genetics & Pharmaceutical, Genome Biology, Image Processing/Computing, Infectious Disease Immunodiagnostics, Mechanisms of infection by SARS-CoV-2, Medical Imaging Technology, Mutagenesis, Population Health Management, Proteins, SARS-CoV-2, SARS-CoV-2 circulating variants , SARS-CoV-2 Viral Variants, Uncategorized, Vaccinology, Variation in human protein-coding regions, virology, Virology - Vector-borne DIsease, Virtual Drug Molecule Screening targeting SAR-CoV-2 proteins, tagged ACE2 receptor, Antibody, Boston Children's Hospital, cryo-electron microscopy, D614G mutation, genetic code, SARS-CoV-2 Entry Factors, spike protein, vaccine development on April 10, 2021| Leave a Comment »

Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure.

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

SARS-CoV-2, the virus that causes COVID-19, has had a major impact on human health globally; infecting a massive quantity of people around 136,046,262 (John Hopkins University); causing severe disease and associated long-term health sequelae; resulting in death and excess mortality, especially among older and prone populations; altering routine healthcare services; disruptions to travel, trade, education, and many other societal functions; and more broadly having a negative impact on peoples physical and mental health.

It’s need of the hour to answer the questions like what allows the variants of SARS-CoV-2 first detected in the UK, South Africa, and Brazil to spread so quickly? How can current COVID-19 vaccines better protect against them?

Scientists from the Harvard Medical School and the Boston Children’s Hospital help answer these urgent questions. The team reports its findings in the journal “Science” a paper entitled “Structural impact on SARS-CoV-2 spike protein by D614G substitution”. The mutation rate of the SARS-CoV-2 virus has rapidly evolved over the past few months, especially at the Spike (S) protein region of the virus, where the maximum number of mutations have been observed by the virologists.

Bing Chen, HMS professor of pediatrics at Boston Children’s, and colleagues analyzed the changes in the structure of the spike proteins with the genetic change by D614G mutation by all three variants. Hence they assessed the structure of the coronavirus spike protein down to the atomic level and revealed the reason for the quick spreading of these variants.

This model shows the structure of the spike protein in its closed configuration, in its **original D614 form** (left) and its **mutant form (G614)**. In the mutant spike protein, the 630 loop (in red) stabilizes the spike, preventing it from flipping open prematurely and rendering SARS-CoV-2 more infectious.

Fig. 1. Cryo-EM structures of the full-length SARS-CoV-2 S protein carrying G614.

(A) Three structures of the G614 S trimer, representing a closed, three RBD-down conformation, an RBD-intermediate conformation and a one RBD-up conformation, were modeled based on corresponding cryo-EM density maps at 3.1-3.5Å resolution. Three protomers (a, b, c) are colored in red, blue and green, respectively. RBD locations are indicated. (B) Top views of superposition of three structures of the G614 S in (A) in ribbon representation with the structure of the prefusion trimer of the D614 S (PDB ID: 6XR8), shown in yellow. NTD and RBD of each protomer are indicated. Side views of the superposition are shown in fig. S8.

IMAGE SOURCE: Bing Chen, Ph.D., Boston Children’s Hospital, https://science.sciencemag.org/content/early/2021/03/16/science.abf2303

The work

The mutant spikes were imaged by Cryo-Electron microscopy (cryo-EM), which has resolution down to the atomic level. They found that the D614G mutation (substitution of in a single amino acid “letter” in the genetic code for the spike protein) makes the spike more stable as compared with the original SARS-CoV-2 virus. As a result, more functional spikes are available to bind to our cells’ ACE2 receptors, making the virus more contagious.

**Fig. 2. Cryo-EM revealed how the D614G mutation changes SARS-CoV-2 spike protein structure.**

IMAGE SOURCE: Zhang J, et al., Science

Say the original virus has 100 spikes,” Chen explained. “Because of the shape instability, you may have just 50 percent of them functional. In the G614 variants, you may have 90 percent that is functional. So even though they don’t bind as well, the chances are greater and you will have an infection

Forthcoming directions by Bing Chen and Team

The findings suggest the current approved COVID-19 vaccines and any vaccines in the works should include the genetic code for this mutation. Chen has quoted:

Since most of the vaccines so far—including the Moderna, Pfizer–BioNTech, Johnson & Johnson, and AstraZeneca vaccines are based on the original spike protein, adding the D614G mutation could make the vaccines better able to elicit protective neutralizing antibodies against the viral variants

Chen proposes that redesigned vaccines incorporate the code for this mutant spike protein. He believes the more stable spike shape should make any vaccine based on the spike more likely to elicit protective antibodies. Chen also has his sights set on therapeutics. He and his colleagues are further applying structural biology to better understand how SARS-CoV-2 binds to the ACE2 receptor. That could point the way to drugs that would block the virus from gaining entry to our cells.

In January, the team showed that a structurally engineered “decoy” ACE2 protein binds to SARS-CoV-2 200 times more strongly than the body’s own ACE2. The decoy potently inhibited the virus in cell culture, suggesting it could be an anti-COVID-19 treatment. Chen is now working to advance this research into animal models.

Main Source:

Abstract

Substitution for aspartic acid by glycine at position 614 in the spike (S) protein of severe acute respiratory syndrome coronavirus 2 appears to facilitate rapid viral spread. The G614 strain and its recent variants are now the dominant circulating forms. We report here cryo-EM structures of a full-length G614 S trimer, which adopts three distinct prefusion conformations differing primarily by the position of one receptor-binding domain. A loop disordered in the D614 S trimer wedges between domains within a protomer in the G614 spike. This added interaction appears to prevent premature dissociation of the G614 trimer, effectively increasing the number of functional spikes and enhancing infectivity, and to modulate structural rearrangements for membrane fusion. These findings extend our understanding of viral entry and suggest an improved immunogen for vaccine development.

https://science.sciencemag.org/content/early/2021/03/16/science.abf2303?rss=1

Other Related Articles published in this Open Access Online Scientific Journal include the following:

COVID-19-vaccine rollout risks and challenges

Reporter : Irina Robu, PhD

https://pharmaceuticalintelligence.com/2021/02/17/covid-19-vaccine-rollout-risks-and-challenges/

COVID-19 Sequel: Neurological Impact of Social isolation been linked to poorer physical and mental health

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2021/03/30/covid-19-sequel-neurological-impact-of-social-isolation-been-linked-to-poorer-physical-and-mental-health/

Reporter: Aviva Lev-Ari, PhD, RN

COVID-19 T-cell immune response map, immunoSEQ T-MAP COVID for research of T-cell response to SARS-CoV-2 infection

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/11/20/covid-19-t-cell-immune-response-map-immunoseq-t-map-covid-for-research-of-t-cell-response-to-sars-cov-2-infection/

Tiny biologic drug to fight COVID-19 show promise in animal models

Reporter : Irina Robu, PhD

https://pharmaceuticalintelligence.com/2020/10/11/tiny-biologic-drug-to-fight-covid-19-show-promise-in-animal-models/

Miniproteins against the COVID-19 Spike protein may be therapeutic

Reporter: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/09/30/miniproteins-against-the-covid-19-spike-protein-may-be-therapeutic/

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Black doctors’ group creates panel to vet Covid-19 vaccines

Posted in COVID-19, Economic Impact of Coronavirus Pandemic, Population Health Management, Genetics & Pharmaceutical, tagged black community, Clinical Trials, COVID-19, vaccine development on September 28, 2020| Leave a Comment »

Black doctors’ group creates panel to vet Covid-19 vaccines

Reporter : Irina Robu, PhD

A group of black physicians have been working on creating their own expert task force to vet regulators’ decisions about COVID-19 drugs and vaccines, due to the fact that the trust in federal agencies has weakened over the last few months.

According to the president of NMA, Leon McDougle, the new task force will address the suspicion around COVID-19 vaccines. The fear is that the vaccines might not be safe or properly tested before they are approved which makes it the reason some patients of color are wary about taking part in the clinical trials. The task force will evaluate how well the clinical trials participants characterize demographic breakdown of American population and the fairness of the federal plans to distribute a vaccine to Black, Latino and Native American communities.

The leaders of the black community task force are still figuring out how it will work and what happens if FDA authorizes the use of product without releasing the full data to support it. As past president of the NMA, Dr. Rodney Hood knows that the organization has in its ranks the kind of expertise that could analyze clinical trial data along with expertise in epidemiology and infectious disease.

The black community task force hopes that they are able to tell their patients about the scientific findings regarding COVID-19 vaccine with full transparency and disclosure.

SOURCE

https://www.statnews.com/2020/09/21/black-doctors-group-creates-panel-to-vet-covid19-vaccines/?utm_source=STAT+NewslettersTop of Form

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Online Event: Vaccine matters: Can we cure coronavirus? An AAAS Webinar

Posted in Biomarkers: Inflammation, Coronavirus Gene Expression, COVID-19, COVID-19, COVID-19: Pandemic Surgery Guidance, Economic Impact of Coronavirus Pandemic, Immune-Mediation (independent immunopathology: lung and reticuloendothelial system), number of asymptomatic infections, Population Health Management, REAL TIME Conference Coverage Twitter's Hashtags and Handles per Presentation/session, SARS-CoV-2, SARS-COV2 Hijacking the Complement and Coagulation Systems, Scientific & Biotech Conferences: Press Coverage, Seasonality & Environmental Factors in Resurgence, Small Molecules in Development of Therapeutic Drugs, Treatment Protocols for COVID-19, Vaccinology, Virology, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged covid19, SARS-CoV-2, vaccine development on August 12, 2020| Leave a Comment »

Online Event: Vaccine matters: Can we cure coronavirus? An AAAS Webinar on COVID19: 8/12/2020

Reporter: Stephen J. Williams. PhD

Source: Online Event

Top on the world’s want list right now is a coronavirus vaccine. There is plenty of speculation about how and when this might become a reality, but clear answers are scarce.Science/AAAS, the world’s leading scientific organization and publisher of the Science family of journals, brings together experts in the field of coronavirus vaccine research to answer the public’s most pressing questions: What vaccines are being developed? When are we likely to get them? Are they safe? And most importantly, will they work?

link: https://view6.workcast.net/AuditoriumAuthenticator.aspx?cpak=1836435787247718&pak=8073702641735492

Presenters

Speaker: Sarah Gilbert, Ph.D.

University of Oxford
Oxford, UK
View Bio

Speaker: Kizzmekia Corbett, Ph.D.

National Institute of Allergy and Infectious Diseases, NIH
Bethesda, MD
View Bio

Speaker: Kathryn M. Edwards, M.D.

Vanderbilt Vaccine Research Program
Nashville, TN
View Bio

Speaker: Jon Cohen

Science/AAAS
San Diego, CA
View Bio

Moderator: Sean Sanders, Ph.D.

Science/AAAS
Washington, DC
View Moderator Bio

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National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Posted in Biomarkers: Inflammation, Coronavirus Gene Expression, Drug Development Process, Economic Impact of Coronavirus Pandemic, FDA, FDA, CE Mark & Global Regulatory Affairs: process management and strategic planning - GCP, GLP, ISO 14155, Inflammatory Pathophysiology, number of asymptomatic infections, Pharmaceutical Discovery, Population genetics, SARS-CoV-2, Systemic Inflammatory Response Related Disorders, Treatment Protocols for COVID-19, Vaccinology, Virus Infective Acute Respiratory Syndrome: SARS-CoV, tagged #COVID-19, Anthony Fauci, Coronavirus Vaccines, interview with scientific leaders, National Public Radio, neutralizing antibody, NPR, pharmaceutical development, SARS-CoV-2, vaccine development on July 19, 2020| Leave a Comment »

National Public Radio interview with Dr. Anthony Fauci on his optimism on a COVID-19 vaccine by early 2021

Reporter: Stephen J. Williams, PhD

Below I am giving a link to an important interview by NPR’s Judy Woodruff with Dr. Anthony Fauci on his thoughts regarding the recent spikes in cases, the potential for a COVID-19 vaccine by next year, and promising therapeutics in the pipeline. The interview link is given below however I will summarize a few of the highlights of the interview.

Some notes on the interview

Judy Woodruff began her report with some up to date news regarding the recent spike and that Miami Florida has just ordered the additional use of facemasks. She asked Dr. Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases (NIAD), about if the measures currently in use are enough to bring this spike down. Dr. Fauci said that we need to reboot our efforts, mainly because people are not doing three things which could have prevented this spike mainly

universal wearing of masks
distancing properly from each other
close the bars and pubs (see Wisconsin bars packed after ruling)

It hasn’t been a uniform personal effort

Dr. Fauci on testing

We have to use the tests we have out there efficiently and effectively And we have to get them out to the right people who can do the proper identification, isolation, and do proper contract tracing and need to test more widely in a surveillance way to get a feel of the extent and penetrance of this community spread. there needs to be support and money for these testing labs

We have a problem and we need to admit and own it but we need to do the things we know are effective to turn this thing around.

On Vaccines

“May be later this year”

His response to Merck’s CEO Ken Frazer who said officials are giving false hop if they say ‘end of year’ but Dr. Fauci disagrees. He says a year end goal is not outlandish.

What we have been doing is putting certain things in line with each other in an unprecedented way.

Dr. Fauci went on to say that, in the past yes, it took a long time, even years to develop a vaccine but now they have been able to go from sequence of virus to a vaccine development program in days, which is unheard of. Sixty two days later we have gone into phase 1 trials. the speed at which this is occurring is so much faster. He says that generally it would take a couple of years to get a neutralizing antibody but we are already there. Another candidate will be undergoing phase 3 trials by end of this month (July 2020).

He is “cautiously optimistic” that we will have one or more vaccines to give to patients by end of year because given the amount of cases it will be able to get a handle on safety and efficacy by late fall.

Now he says the game changer is that the government is working with companies to ramp up the production of doses of the candidate vaccines so when we find which one works we will have ample doses on hand. He is worried about the anti vaccine movement derailing vaccine testing and vaccinations but says if we keep on informing the public we can combat this.

Going back to school

Dr. Fauci is concerned for the safety of the vulnerable in schools, including students and staff. He wants the US to get down to a reasonable baseline of cases but in the US that baseline after the first wave was still significantly higher than in most countries, where the baseline was more like tens of cases not hundreds of cases.

For more information on COVID-19 Please go to our Coronavirus Portal at

https://pharmaceuticalintelligence.com/coronavirus-portal/

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Promises on Covid-19 Vaccines

Posted in COVID-19, Population Health Management, Genetics & Pharmaceutical, Treatment Protocols for COVID-19, Vaccinology, tagged COVID-19, Immunology, RNA vaccine, vaccine development on May 11, 2020| Leave a Comment »

Promises on Covid-19 Vaccines

Reporter: Irina Robu, PhD

Vaccines play a vital role in keeping us healthy. Currently, scientists are racing through development at speeds never before seen. Even if the stages of vaccine development could be compressed and supplies could be quickly manufactured, it could take months or longer before people can have access to it.

The World Health Organization closely monitors Covid-19 vaccines which are designed in academic laboratories without having the commercial production capacity. Whereas China has widespread vaccine production capacity and other developing countries including India, Indonesia, and Brazil are amongst the world’s largest vaccine producers and exporters, a sizable amount of the manufacturing capacity belonging to pharmaceutical companies that sell vaccine in North America and Europe is based in the United States.

Assuming a vaccine can be developed rapidly, the production of some vaccine candidates could be easily ramped up than others it is conceivable that they could use the existing plants to produce more vaccines. Production of this type of candidate could reach hundreds of millions of doses within about a year, yet any vaccines would require longer time to reach those output levels.

An RNA vaccine project is being developed by Pfizer and BioNTech, began testing four possible vaccines in a compressed Phase ½ trial in the US on May 5, 2020. In addition, Moderna signed a deal with pharmaceutical company Lonzo to produce 1 billion doses of the vaccine in the U.S. and in Switzerland. Nevertheless, of who gets vaccines, it is believed that most new vaccines will require at least two doses to be effective, so any estimates of numbers of doses available in the autumn will need to be divided by two to find out how many people could expect to be vaccinated. The public, both in US and abroad need clear communications about realistic times to COVID-19 vaccine access. Yet when vaccines do start to become available, demand will be enormous and supply will be minimal.

SOURCE