HIV Vaccine Uses mRNA technology

An experimental HIV vaccine that uses the same technology as the COVID-19 mRNA vaccines from Moderna and Pfizer is showing promising results in both monkeys and mice. A press release from the National Institute of Allergy and Infectious Diseases (NIAID) explained that monkeys who received a multiple doses of the experimental vaccine had their chances of contracting an HIV-like virus lowered by 79%.

Scientists have spent decades struggling to create an HIV vaccine due to the speed at which the virus mutates and its remarkable ability to evade the immune system. Dr. Anthony Fauci, president of NIAID, leader of the United States’ battle against COVID-19, and a co-author of this HIV vaccine study published in Nature Medicine, expressed optimism about the progress made by the mRNA technology.

Despite nearly four decades of effort by the global research community, an effective vaccine to prevent HIV remains an elusive goal,” Fauci said. “This experimental mRNA vaccine combines several features that may overcome shortcomings of other experimental HIV vaccines and thus represents a promising approach.”

The trial involved a series of booster shots in macaques over the course of an entire year. The authors explained that not only did the trial yield a positive immune response, but also that “the vaccine was well tolerated with only mild adverse events after each inoculation,” with the most common side effect being loss of appetite.

Now the researchers are working on refining the process so less rounds of shots are needed, as they noted in Nature Medicine that “a vaccination regimen encompassing seven or more sequential immunizations would be difficult to implement in humans.” The study’s leader Dr. Paolo Lusso, said that if the team is successful at reducing the number of boosters in a safe and effective way, they will then move on to a phase 1 trial of the vaccine in adult humans.

Source: https://www.lgbtqnation.com/

Boris Johnson: UK faces ‘tidal wave’ of omicron cases

Prime Minister Boris Johnson warned Sunday that Britain faces a “tidal wave” of infections from the omicron coronavirus variant, and announced a huge increase in booster vaccinations to strengthen defenses against it. In a televised statement, Johnson said everyone age 18 and older will be offered a third shot of vaccine by the end of this month in response to the omicronemergency.” The previous target was the end of January.

He said cases of the highly transmissible variant are doubling every two to three days in Britain, and “there is a tidal wave of omicron coming.”

And I’m afraid it is now clear that two doses of vaccine are simply not enough to give the level of protection we all need,” Johnson said. “But the good news is that our scientists are confident that with a third dose – a booster dose – we can all bring our level of protection back up.”

He announced a “national mission” to deliver booster vaccines, with pop-up vaccination centers and seven-day-a-week getting extra support from teams of military planners and thousands of volunteer vaccinators. Johnson’s Dec. 31 target applies to England. The other parts of the U.K. — Scotland, Wales and Northern Ireland — are also expected to speed up their vaccination campaigns.

The U.K. Health Security Agency says existing vaccines appear less effective in preventing symptomatic infections in people exposed to omicron, though preliminary data show that effectiveness appears to rise to between 70% and 75% after a third vaccine dose.

Source: https://www.startribune.com/

Moderna says an omicron variant vaccine could be ready in early 2022

Modernas Chief Medical Officer Paul Burton said Sunday the vaccine maker could roll out a reformulated vaccine against the omicron coronavirus variant early next year. It’s not clear whether new formulations will be needed, or if current Covid vaccinations will provide protection against the new varianthat has begun to spread around the globe.

We should know about the ability of the current vaccine to provide protection in the next couple of weeks, but the remarkable thing about the MRNA vaccines, Moderna platform is that we can move very fast,” Burton said on BBC’s “Andrew Marr Show.”

The emergence of a new COVID-19 variant sparked a big rally in shares of Moderna on Monday as the company announced plans to combat the virus with more vaccines. Moderna jumped as much as 10% on Monday, extending its two-day rally to more than 30% amid budding fears of the Omicron variant.

https://www.cnbc.com/

Nasal Vaccine to prevent Alzheimer’s

Brigham and Women’s Hospital will test the safety and efficacy of a nasal vaccine aimed at preventing and slowing Alzheimer’s disease, the Boston hospital announced Tuesday. The start of the small, Phase I clinical trial comes after nearly 20 years of research led by Howard L. Weiner, MD, co-director of the Ann Romney Center for Neurologic Diseases at the hospital.

The trial will include 16 participants between the ages of 60 and 85, all with early symptomatic Alzheimer’s but otherwise generally healthy. They will receive two doses of the vaccine one week apart, the hospital said in a press release. The participants will enroll from the Ann Romney Center.

A Phase I clinical trial is designed to establish the safety and dosage for a potential new medication. If it goes well, a much larger trial would be needed to test its effectiveness. The vaccine uses a substance called Protollin, which stimulates the immune system. “Protollin is designed to activate white blood cells found in the lymph nodes on the sides and back of the neck to migrate to the brain and trigger clearance of beta amyloid plaques — one of the hallmarks of AD [Alzheimer’s disease],” the hospital explains. It notes that Protollin has been found to be safe in other vaccines.

The launch of the first human trial of a nasal vaccine for Alzheimer’s is a remarkable milestone,” said Weiner in the hospital’s press release. “Over the last two decades, we’ve amassed preclinical evidence suggesting the potential of this nasal vaccine for AD. If clinical trials in humans show that the vaccine is safe and effective, this could represent a nontoxic treatment for people with Alzheimer’s, and it could also be given early to help prevent Alzheimer’s in people at risk.”

The researchers say they aim to “determine the safety and tolerability of the nasal vaccine” in the trial and observe how Protollin affects participants’ immune response, including how it affects their white blood cells.

The immune system plays a very important role in all neurologic diseases,” Weiner added. “And it’s exciting that after 20 years of preclinical work, we can finally take a key step forward toward clinical translation and conduct this landmark first human trial.”

Source: brighamandwomens.org
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https://www.cbsnews.com/

New Vaccine is Targeting All Coronaviruses

Army scientists working on a vaccine to target all coronaviruses, including mutations of the one causing COVID-19 and others that may emerge in the future, are finding data from early human trials promising and expect to publish the results by year-end.

Researchers at the Walter Reed Army Institute of Research have been working since the start of the COVID-19 pandemic on a pan-coronavirus vaccine and are currently analyzing data from the Phase I clinical trial, which began in April with dozens of volunteers. They are following up with participants to monitor the safety and effectiveness of the new vaccine one month after each received their last dose.

Everything that we have been seeing from early stages of design of our vaccine and testing, in all different animal species, has really just been consistent and predictive of a very good response,” Kayvon Modjarrad, director of Walter Reed’s Emerging Infectious Diseases Branch, said in an interview. “Indications are that we are on that same pathway.”

The Walter Reed vaccine — called SpFN — may eventually be used by people who have already received other COVID-19 vaccines “as a bridge towards providing individuals continued, broad, long-term immunity for SARS-like viruses, whether they be variants that emerge in the future or new species of SARS viruses,” Modjarrad said.

The SpFN vaccine deploys a soccer ball-shaped protein that can target the spikes of multiple coronavirus strains on its different faces.

Source: https://www.bradenton.com/

mRNA Vaccines will Soon Prevent Cancer

In the early 1990s, mRNA technology emerged as an alternative to traditional vaccine development, building on research conducted by Wolff et al. involving direct gene transfer into mouse muscle in vivo. Initially, mRNA technology came with drawbacks as it caused severe inflammation upon administration, degraded quickly in the body and was difficult to move across the membrane into the cell. However, breakthroughs using nanotechnology overcame some of these challenges; scientists encased the RNA and used synthetic RNA that the body’s immune system recognizes.

Other major technological innovation and research investment has improved the delivery, translation and stability, enabling mRNA to become a promising tool for vaccine development. These breakthroughs have allowed further research and development of mRNA vaccines, particularly against viruses such as HIV and influenza. In 2020, when the COVID-19 pandemic hit, several human clinical trials were underway to test mRNA vaccines against influenza and HIV. As a result of the pandemic, research efforts, funding and facilities prioritized the development of mRNA vaccines for COVID-19. Combined efforts of global research teams working on COVID-19 mRNA vaccinations accelerated the field of research, improving the knowledge, understanding and methods of mRNA vaccine technology. This allowed the progression of mRNA vaccines for other diseases, such as cancer, and clinical trials for mRNA cancer vaccinations are now underway. The MD Anderson Cancer Center (TX, USA) is conducting a clinical trial to test whether mRNA technology can be used to prevent the recurrence of colorectal cancer.


A B cell displays antibodies specific to antigens on a colorectal cancer cell and signals killer T cells to destroy it.

People with colorectal cancer often undergo surgery to remove the cancerous tumor; however, cancer cells remain in the body and shed DNA into the bloodstream, which is known as circulating tumor DNA (ctDNA) and can cause further complications and metastasis. Van Morris and Scott Kopetz are leading the Phase II trial (NCT04486378) for a personalized mRNA cancer vaccine. People who have stage II or III colorectal cancer are given a blood test after their surgery to check for ctDNA. The patient’s tumor tissue is genetically profiled to identify mutations that fuel cancer growth. The tumor mutations are then ranked from the most to the least common to create a personalized mRNA vaccine for the patient. “We’re hopeful that with the personalized vaccine, we’re priming the immune system to go after the residual tumor cells, clear them out and cure the patient,” explains Morris.

Source: https://www.future-science.com/

Moderna Is Testing new Vaccine Stored in Refrigerators, no More in Freezers

Moderna Inc said it had dosed the first participant in an early-stage study of a new COVID-19 vaccine candidate that could potentially be stored and shipped in refrigerators instead of freezers. The company said its new candidate could make it easier for distribution, especially in developing countries where supply chain issues could hamper vaccination drives.

The early-stage study will assess the safety and immunogenicity of the next-generation vaccine, designated as mRNA-1283, at three dose levels, and will be given to healthy adults either as a single dose or in two doses 28 days apart, the company said. Moderna also plans to evaluate the new vaccine, mRNA-1283, as a potential booster shot in future studies.

Last week, Moderna began dosing the first participants in a study testing COVID-19 booster vaccine candidates targeting the variant, known as B.1.351, that first emerged in South Africa.

The booster vaccine candidates, designated mRNA-1273.351, will be tested in a trial of both a variant-specific shot and a multivalent shot, according to the company’s announcement.

New Nanoparticle-delivered COVID-19 Vaccine

Researchers from Cleveland Clinic’s Global Center for Pathogen Research & Human Health have developed a promising new COVID-19 vaccine candidate that utilizes nanotechnology and has shown strong efficacy in preclinical disease models.

According to new findings published in mBio, the vaccine produced potent neutralizing antibodies among preclinical models and also prevented infection and disease symptoms in the face of exposure to SARS-CoV-2 (the virus that causes COVID-19). An additional reason for the vaccine candidate’s early appeal is that it may be thermostable, which would make it easier to transport and store than currently authorized COVID-19 vaccines.

Our vaccine candidate delivers antigens to trigger an immune response via nanoparticles engineered from ferritin–a protein found in almost all living organisms,” said Jae Jung, PhD, director of the Global Center for Human Health & Pathogen Research and co-senior author on the study. “This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, including that it does not require strict temperature control.”

Added Dokyun (Leo) Kim, a graduate student in Dr. Jung’s lab and co-first author on the study, “This would dramatically ease shipping and storage constraints, which are challenges we’re currently experiencing in national distribution efforts. It would also be beneficial for distribution to developing countries.”

Other benefits of the protein nanoparticles include minimizing cellular damage and providing stronger immunity at lower doses than traditional protein subunit vaccines against other viruses, like influenza.

The team’s vaccine uses the ferritin nanoparticles to deliver tiny, weakened fragments from the region of the SARS-CoV-2 spike protein that selectively binds to the human entry point for the virus (this fragment is called the receptor-binding domain, or RBD). When the SARS-CoV-2 RBD binds with the human protein called ACE2 (angiotensin-converting enzyme 2), the virus can enter host cells and begin to replicate.

The researchers tested their vaccine candidate on a ferret model of COVID-19, which reflects the human immune response and disease development better than other preclinical models. Dr. Jung, a foremost authority in virology and virus-induced cancers, previously developed the world’s first COVID-19 ferret model–a discovery that has significantly advanced research into SARS-CoV-2 infection and transmission.

Source: https://www.lerner.ccf.org/
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https://www.eurekalert.org/

New Variant of SARS-CoV-2 Spreading Fast

A coronavirus variant called B1525 has become one of the most recent additions to the global variant watch list and has been included in the list of variants under investigation by Public Health England.

Scientists are keeping a watchful eye on this variant because it has several mutations in the gene that makes the spike protein – the part of the virus that latches onto human cells. These changes include the presence of the increasingly well-known mutation called E484K, which allows the virus to partly evade the immune system, and is found in the variants first identified in South Africa (B1351) and Brazil (P1).

While there is no information on what this means for B1525, there is growing evidence that E484K may impact how effective COVID vaccines are. But there is no suggestion so far that B1525 is more transmissible or that it leads to more severe disease.

There are other mutations in B1525 that are also noteworthy, such as Q677H. Scientists have repeatedly detected this changeat least six times in different lineages in the US, suggesting that it gives the virus an advantage, although the nature of any benefit has not been identified yet.

The B1525 variant also has several deletions – where “letters” (G, U, A and C) of the virus’s RNA are missing from its genome. These letters are also missing in B117, the variant first detected in Kent, England. Research by Ravindra Gupta, a clinical microbiologist at the University of Cambridge, found that these deletions may increase infectivity twofold in laboratory experiments.

As with many variants, B1525 appears to have emerged quite recently. The earliest example in the shared global database of coronavirus genomes, called Gisaid, dates from 15 December 2020. It was identified in a person in the UK. And like many variants, B1525 had already travelled the world before it came to global attention. A total of 204 sequences of this variant in Gisaid can be traced to 18 countries as of 20 February 2021.

Source: https://theconversation.com/

COVID-19 Vaccine AstraZeneca confirms 100% protection against severe disease, hospitalisation and death

The primary analysis of the Phase III clinical trials from the UK, Brazil and South Africa, published as a preprint in The Lancet confirmed COVID-19 Vaccine AstraZeneca is safe and effective at preventing COVID-19, with no severe cases and no hospitalisations, more than 22 days after the first dose.

Results demonstrated vaccine efficacy of 76% (CI: 59% to 86%) after a first dose, with protection maintained to the second dose. With an inter-dose interval of 12 weeks or more, vaccine efficacy increased to 82% (CI: 63%, 92%).

The analysis also showed the potential for the vaccine to reduce asymptomatic transmission of the virus, based on weekly swabs obtained from volunteers in the UK trial. The data showed that PCR positive readings were reduced by 67% (CI: 49%, 78%) after a single dose, and 50% (CI: 38% to 59%) after the two dose regimen, supporting a substantial impact on transmission of the virus.

The primary analysis for efficacy was based on 17,177 participants accruing 332 symptomatic cases from the Phase III UK (COV002), Brazil (COV003) and South Africa (COV005) trials led by Oxford University and AstraZeneca, a further 201 cases than previously reported.

“This primary analysis reconfirms that our vaccine prevents severe disease and keeps people out of hospital. In addition, extending the dosing interval not only boosts the vaccine’s efficacy, but also enables more people to be vaccinated upfront. Together with the new findings on reduced transmission, we believe this vaccine will have a real impact on the pandemic,”said Sir Mene Pangalos, Executive Vice President BioPharmaceuticals R&D.

These new data provide an important verification of the interim data that has helped regulators such as the MHRA in the UK and elsewhere around the world to grant the vaccine emergency use authorisation. It also helps to support the policy recommendation made by the Joint Committee on Vaccination and Immunisation for a 12-week prime-boost interval, as they look for the optimal approach to roll out, and reassures us that people are protected 22 days after a single dose of the vaccine,” explained Professor Andrew Pollard, Chief Investigator of the Oxford Vaccine Trial, and co-author of the paper.

Data will continue to be analysed and shared with regulators around the world to support their ongoing rolling reviews for emergency supply or conditional approval during the health crisis. AstraZeneca is also seeking Emergency Use Listing from the World Health Organization for an accelerated pathway to vaccine availability in low-income countries.

The vaccine can be stored, transported and handled at normal refrigerated conditions (two-eight degrees Celsius/36-46 degrees Fahrenheit) for at least six months and administered within existing healthcare settings.

Source: https://www.astrazeneca.com/