Vaccines for Children: List By Age, Benefits, Safety

Fears Grow Over The Future Of MRNA Vaccine Research In The US

Researchers are increasingly concerned about the future of messenger RNA (mRNA) vaccine research in the US. Initial worries were sparked by a US National Institutes of Health (NIH) review of the studies it funds in this area, while staff cuts at agencies that support this type of research have added to scientists' fears.

'Despite the promise of this technology … we are risking squandering our leadership in the mRNA space in the 21st century,' Jeff Coller, an expert on RNA biology from Johns Hopkins University (JHU) in Maryland, warned at a media briefing about the potential of mRNA medicines on 10 April.

'NIH [funded] researchers across the US are being targeted for projects involving mRNA vaccines,' he stated. 'Based on what we have seen in other research areas, the next steps could be for the administration to halt funding for projects that are developing these breakthrough mRNA therapeutics.'

Coller also highlighted 'the huge cuts in experienced staff' at the US Food and Drug Administration, and in particular the resignation of Peter Marks, the long-time director of the agency's unit that regulates vaccines and other biological products. Such departures raise significant questions about whether the US will maintain its leadership within this sector, he suggested.

mRNA projects lose budgets, partnerships and jobs

According to Coller, there are currently over 700 potential medicines based on mRNA at the preclinical development stage across academia and industry, and 267 in clinical development. Most of this activity is housed at companies located within the US, with around 65% of the 150,000 people working globally on mRNA research based in the country.

But Coller warned that 'skittishness' across the industry could see projects moved overseas, due to companies' concerns about the situation in the US.

Surveys of 100 senior life science professionals in the field, conducted in late March by the Alliance for mRNA Medicines that Coller helped found, indicated that about 30% would consider relocating their operations overseas if the US pulled away from investment in mRNA technology.

According to Coller, almost half of those surveyed reported already experiencing negative effects from policies enacted under President Donald Trump's second administration. These impacts include the reduction in the scope of projects, budget reductions, delayed capital investments, partnership terminations, job losses and hiring freezes, and relocation of projects or divisions at their companies to other shores, Coller said.

'Indeed, in conversations with our members, strategic partnerships have been lost because NIH funding has been cut, and companies are already looking overseas to turn their manufacturing operations into other countries,' he stated.

Amid 'the threat of indiscriminate cuts' to mRNA programmes in the US, Coller noted that governments in China, the EU, Australia and Brazil appear to be doubling down on their investments in this technology.

Meanwhile the deputy director of JHU's comprehensive cancer centre Elizabeth Jaffee, an oncologist focused on immune-based therapies for pancreatic and breast cancers, is worried that her NIH grant that funds research on an mRNA-based pancreatic cancer vaccine could be stopped, along with the ongoing associated clinical trial.

'We are very concerned, and our patients are concerned,' Jaffee stated at the JHU briefing. 'We don't have a lot of funding for doing these trials beyond the NIH, and the way things are going … you are told a day in advance that your grant is cut.'

In the meantime, Coller said that Republican lawmakers in at least seven states have introduced state measures to ban or restrict the usage of mRNA in treating various health disorders.

In response to questions Chemistry World raised about researchers' concerns over grant terminations and delays, and the threat of mRNA medical research projects moving overseas, an NIH spokesperson said: 'NIH is taking action to terminate research funding that is not aligned with NIH and HHS priorities. We remain dedicated to restoring our agency to its tradition of upholding gold-standard, evidence-based science.'

'As we begin to make America healthy again, it's important to prioritise research that directly affects the health of Americans. We will leave no stone unturned in identifying the root causes of the chronic disease epidemic as part of our mission to make America healthy again,' they added.

States Echo RFK Jr. Agenda In Push For Ban On Vaccine Mandates

State legislators are moving to advance US Health and Human Services Secretary Robert F. Kennedy Jr.'s push for greater scrutiny of vaccines, introducing a wave of bills that would limit or ban the use of messenger RNA shots and prohibit vaccine mandates.

Idaho this month passed a first-of-its-kind law prohibiting vaccine requirements as a condition for employment or school attendance. At least 15 other states have pending bills seeking to ban Covid-19 or mRNA vaccine mandates, establish a vaccine bill of rights, or prohibit any immunization containing mRNA material. Some bills would require manufacturers to label foods containing mRNA, according to data compiled by Bloomberg Government.

The bills echo Kennedy's skepticism of vaccine safety, which includes promoting discredited theories and holding positions connected to an anti-vaccine group. Proposed prohibitions on mandates have come up in previous state legislature sessions, but momentum is ramping up with a secretary that shares supporting views, attorneys say.

"There's been this underlying freedom of choice movement that's been there for a long time around vaccines," said Richard H. Hughes IV, a member at Epstein Becker & Green PC and an expert on vaccine access.

"This is like a populist movement behind President Trump, sort of spurred on by the Covid-19 pandemic, which meets up with Robert F. Kennedy Jr.," Hughes said. "You blend all this together, and we're living in a time where anti-vaccine policy is finding its way into the books."

Kennedy promised to review the science behind vaccine safety and childhood immunization schedules, but he's faced pushback from public health advocates who say the move ignores safety data approved by federal regulators.

His messaging about vaccine effectiveness has also been inconsistent—specifically amid a measles outbreak across the US that has killed two unvaccinated children in Texas.

Kennedy wrote in an April 5 post on X that the "most effective way to prevent the spread of measles is the MMR vaccine." It was his clearest endorsement of the measles, mumps, and rubella shot.

Hours later, Kennedy claimed in another post that two Texas doctors "healed" about 300 children with measles by using a steroid treatment and an antibiotic. Neither is proven to treat the viral infection.

Kennedy in an interview with CBS on April 9 said "people should get the measles vaccine," but "the government should not be mandating those." He also raised doubts in the interview about Novavax Inc.'s Covid-19 vaccine.

State Action

Vaccine-related bills introduced in states this year include limiting the use of mRNA technology and broadly prohibiting immunization requirements. They have varying odds of being enacted.

At least 12 states are considering legislation on mRNA vaccines, which trigger an immune response to teach the body how fight a particular virus. Kennedy and others have questioned the safety of the mRNA Covid-19 vaccines, despite the Food and Drug Administration's backing and ongoing safety monitoring.

Republicans in Montana, New York, South Carolina, and Texas are sponsoring bills to prohibit the administration of Covid-19 vaccines or any medical product containing mRNA material, as well as mandates for those products.

In Arkansas, Oklahoma, and Tennessee, legislators want pharmaceutical products to explicitly include mRNA technology in their ingredients list or specify if foods were derived from animals or other sources that received mRNA vaccinations.

Some legislation mirrors the Idaho law, with a Republican-sponsored bill in New York (AB 3807) seeking to establish the right of a person "to determine what is in their own best medical interest without threat to their livelihood, schooling, or freedom of movement."

In Texas, a proposed constitutional amendment (HJR 91) would give residents within the state an "unalienable and natural right to refuse a vaccination."

A bill (HB 357) that passed the New Hampshire state House in March would limit childhood immunization requirements to diseases identified in statute, including mumps, pertussis, and tetanus. It would remove the state health commissioner's authority to adopt rules requiring additional shots and expire existing vaccine mandates for chickenpox and other infections by June 30, 2026.

Democrats in the state have criticized the legislation, arguing it will remove a rigorous decision-making process led by infectious disease professionals and hand responsibility over to legislators with political agendas.

The bill's sponsor, state Rep. Jim Kofalt (R), said in an interview that lawmakers make efforts to weigh the testimony of subject matter experts, but a "mandated medical intervention is a pretty serious matter."

The legislation "really puts the decision-making power into the hands of parents," Kofalt said.

'Freedom of Choice'

Lawmakers and "Make America Healthy Again" proponents say the time is ripe for legislation that prioritizes consumer choice and limits explicit government directives.

"What you have right now is a moment where the citizens of this country are not only engaged and wanting change, they're empowered and believing they have the power to make change," said Del Bigtree, CEO of MAHA Action, a grassroots group promoting Kennedy's agenda.

Bigtree in a press hearing in February said MAHA Action hired professional investigators and scientists to go through bills across the US, determining whether the legislation aligns with the MAHA movement. The tracker would allow the public to view how state representatives are voting on issues related to MAHA, according to Bigtree.

At a press conference in Utah on April 7 promoting MAHA legislation, Kennedy said "it's a moral imperative that we all believe in freedom of choice in this country."

Aimee Pugh Bernard, a professor in the Department of Immunology and Microbiology at the University of Colorado Anschutz Medical Campus, said in an interview that "having choice is a good thing," but "it needs to be based on evidence and science."

She noted that vaccine mandates are essential for individuals who are immunocompromised or too young to receive certain vaccines.

"There are all kinds of people in the community that rely on other people to get vaccinated to shield them from these dangerous diseases," Bernard said.

Scientists Are Optimistic About New COVID-19 Vaccine Studies From Novavax

Novavax, the little-known Maryland company that received a $1.6 billion deal from the federal government for its experimental coronavirus vaccine, announced encouraging results in two preliminary studies on Tuesday.

In one study, 56 volunteers produced a high level of antibodies against the virus without any dangerous side effects. In the other, researchers found that the vaccine strongly protected monkeys from coronavirus infections.

Although it's not possible to directly compare the data from clinical trials of different coronavirus vaccines, John Moore, a virologist at Weill Cornell Medicine who was not involved in the studies, said the Novavax results were the most impressive he had seen so far.

"This is the first one I'm looking at and saying, 'Yeah, I'd take that,'" Moore said.

Angela Rasmussen, a virologist at Columbia University who was not involved in the studies, called them "encouraging preliminary results," but cautioned that it won't be possible to say whether the vaccine is safe and effective until Novavax conducts a large-scale study — known as Phase 3 — comparing people who get vaccinated to people who get a placebo.

The studies are being submitted to scientific journals to be reviewed for publication, said Dr. Gregory Glenn, the president of research and development at Novavax.

The company has said that if its vaccine is shown to be effective, it can produce 100 million doses by the beginning of next year, or enough to give to 50 million people if administered in two doses. Under its deal with the federal government, the company will also receive money to undertake large-scale manufacturing of millions more doses if the vaccine is shown to work.

Novavax's vaccine is one of more than two dozen products to have entered the first round of safety tests in people, known as Phase 1 trials. Five other coronavirus vaccines are already in Phase 3 trials, in which thousands of people are tested to see if a vaccine works.

But Novavax, which has never brought a vaccine to market in its 33-year history, uses a formula that's different from all the other vaccines that have produced results in humans so far.

Its vaccines contain a coronavirus protein that prompts a response from the immune system. Protein-based vaccines have a longer track record than some of the newer approaches used by competing coronavirus vaccines, such as those based on viral genes or so-called adenoviruses.

Protein-based vaccines are licensed for diseases such as hepatitis B and shingles. Novavax successfully completed a Phase 3 trial for a protein-based vaccine for influenza earlier this year and has done research on other diseases, such as Middle East respiratory syndrome.

Novavax's technology turns moth cells into factories for a coronavirus protein called spike, which studs the surface of coronaviruses. Its vaccine combines several of the spike proteins in a nanoparticle.

To improve the performance of the vaccine, Novavax mixed the spike proteins with a compound called an adjuvant. Studies on mice had previously shown that the adjuvant stimulates immune cells so that they develop a potent response to the virus.

The researchers gave the protein and adjuvant to monkeys in different combinations of doses. The monkeys began making high levels of antibodies that could specifically block the coronavirus.

When the monkeys were infected, some versions of the vaccine left them with no trace of the vaccine in their lungs or noses.

"That's pretty remarkable," said Akiko Iwasaki, an immunologist at Yale University. She noted that the Novavax vaccine provided stronger protection for monkeys than have other coronavirus vaccines, such as Moderna's messenger RNA vaccine.

In May, Novavax started a Phase 1 human trial on 134 volunteers. Some of the people who received the vaccine experienced tenderness at the spot where they got injected. But the researchers found no serious side effects.

The researchers extracted serum from the vaccinated volunteers and mixed it with coronaviruses and cells. This showed that the volunteers produced high levels of antibodies that prevented the viruses from infecting cells. The vaccine produced more antibodies in the volunteers than in patients who had recovered from COVID-19 on their own.

"There's no way to know yet what level leads to protection," said Matt Frieman, a virologist at the University of Maryland School of Medicine and a co-author of the Phase 1 study. "But all of these pieces point to it being quite effective."

Volunteers who only received the spike protein in their vaccine did not make a lot of antibodies, the researchers found. "The adjuvant is critical," Glenn of Novavax said.

Moore said that the volunteers' strong response to the vaccine "does not surprise me in the slightest." In June, he and his Weill Cornell colleague P.J. Klasse predicted protein-based vaccines would produce a strong antibody response in a review they published in the Journal of Virology.

Although Novavax is the first company to share clinical results on the immune response of a protein vaccine, it is not the only one testing this technology. Three other protein-based vaccines for COVID-19 — from Clover Biopharmaceuticals, the University of Queensland and Vaxine — are also in Phase 1 trials.

The World Health Organization lists more than 50 protein-based coronavirus vaccines in preclinical trials. One of them is being developed by Sanofi and GlaxoSmithKline, a partnership that last month was granted $2.1 billion from the federal government for 100 million doses. Sanofi expects to start its Phase 1 trial next month.

Sanofi and Novavax both manufacture their vaccines inside the cells of the fall armyworm moth, which allows them to be produced more quickly than older methods that use mammal cells. This technique is one reason Novavax's vaccine candidate has gotten so much attention — in addition to its deal with the U.S. Government, the company has also secured up to $388 million from the nonprofit Coalition for Epidemic Preparedness Innovations, which seeks to make vaccines available outside of the United States. Sanofi's Flublok vaccine, which is already on the market, uses this technology.

Immunologists have been debating the importance of antibodies for fighting the coronavirus. It's possible that another part of the immune system, T cells, is also needed to fend off the virus. Moore speculated that the best vaccine against COVID-19 might marshal both types of responses.

A protein vaccine could provide strong antibody protection, while another vaccine — perhaps one based on messenger RNA or an adenovirus — could enlist T cells.

"If these first-generation vaccines are safe but they're just not potent enough, then you would certainly want to look at combining them," Moore said.

c.2020 The New York Times Company

Originally Published: August 4, 2020 at 8:29 PM EDT

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