On the hunt for climate disease
Moderna's MRNA Norovirus Vaccine Trials: To Hurl Or Not To Hurl. That Is The Endpoint.
Norovirus vaccines face significant hurdles, with virtually no success from past efforts from HilleVax and Vaxxart. But Moderna's mRNA-1403, now in Phase 3 trials, is based on the company's mRNA technology, which controlled the COVID pandemic. Will it work here? Keep a bucket handy, just in case.
When it comes to clinical trials of a norovirus vaccine – something that has been ongoing since the 1970s, it's the Wild West. The early vaccines were crude and the outcomes has been universally dismal. This could change if Moderna hits the mark with mRNA-1403, its experimental mRNA-based norovirus vaccine. More on this later.
Two types of trials
There are two very different types of trials that are used to determine whether such a vaccine might be efficacious. One isn't too bad and the other is seriously bad. Both involve treated and placebo groups, but the similarity ends there.
In challenge trials, participants are deliberately infected with the virus with one group getting a placebo and the other vaccine. This provides a fast, accurate indication of whether the vaccine works and requires relatively few people. The problem is that the participants are being exposed to a nasty pathogen, something that brings up (pun) some ethical issues. All participants are likely to get sick. (How are they exposed? Let your imagination run wild and see if you can figure out how that is done. It's disgusting.)
In population-based trials, a large number of people are followed over time to see if there is a difference between the vaccination and placebo groups. If they catch the bug they will do so naturally. The numbers will tell the story. This is the protocol that Moderna is employing.
What's going to happen to the participants in a challenge trial?
Let's examine the three possible outcomes:
#1 Placebo group: It's only a matter of how much comes out of a given orifice, when, and for how long. You're doomed.
#2 Vaccine-treated group: Assume that the vaccine will be ineffective. See #1.
#3 Challenge trial treated group with an effective vaccine. There aren't any effective vaccines. See #1.
So, unless your bathroom needs a quick makeover the challenge trial should be avoided.
What is Moderna doing?
A press release from the University of Aberdeen (Britain) asks for help in an innocent enough way :
This may sound pretty bad, but it's not.
The university is participating in one of the worldwide clinical trials of Moderna's mRNA-1403, the only messenger RNA-based vaccine currently in clinical trials. The Nova 301 trial is designed to evaluate the vaccine's efficacy in preventing or minimalizing the effects of norovirus (NoV), the so-called "Stomach Flu (1). Moderna is looking to recruit approximately 25,000 people globally to test the vaccine in Phase 3 clinical trials trial, the final phase before approval (or rejection). This will make or break the vaccine. My prediction? I haven't the slightest idea.
Requirements to be in the Moderna trials
Participants need to be 18 or older, in good health, and not have any of a variety of chronic gastrointestinal diseases. There is compensation for participants but Moderna won't reveal how much, saying only "participants are typically reimbursed for their time and any expenses incurred during the study." That doesn't sound so hot. Neither does this: "The Nova 301 Trial team will be available to support everyone who takes part in the trial." Does this include a mop?
HilleVax goes down in flames
There is ample cause for pessimism. Developing a norovirus vaccine is very far from easy. Norovirus has been a target of vaccine research for a long time and there is little to show. Takeda's TAK-214 (a different name for HilleVax's HIL-214, the same vaccine) (2) shows what happens when it fails.
HilleVax's stock price during the past year. You don't need to be Warren Buffet to figure out what happened on July 8th.
Past "achievements," such as they are
HilleVax's HIL-214 was ineffective by any measure. In its NEST-IN1 trial, a randomized, double-blind, placebo-controlled study a vaccine efficacy of 5% was observed. Nor did 214 show any efficacy in any of the secondary outcomes, hence the stock plunge.
Vaxxart has been developing oral vaccines to protect against the two most common NoV genotypes. It has not gone well so far:
While the 85% in viral shedding may look interesting I'm not so sure it's meaningful. NoV is one of the most contagious viruses around; it takes only 10-100 viral particles to cause infection. That ain't much, so it's hard to see how suppressing even 85% of viral shedding of any active infection will make a significant difference in transmission.
Bottom line
mRNA technology was spectacularly successful in helping control COVID. Will it repeat this success here? Unfortunately, we won't know the answer for about two years. Nonetheless, I wish them well.
And the rest of you too. The norovirus season is just getting started.
NOTES:
(1) "Stomach flu" is an inaccurate term. Norovirus and influenza are unrelated.
(2) HilleVax did not use live virus in its trials. Instead, virus-like particles, which cannot cause infection were used.
Africa: The Deadly Comeback Of A Preventable Killer - Measles
Vaccines can prevent the disease, but hundreds of thousands, mostly children, die every year
The world has seen a sharp resurgence of measles, with more than 10 million cases reported globally and 107,500 deaths, mostly among children under five, according to the World Health Organization (WHO) and the United States Centers for Disease Control and Prevention (CDC). The alarming increase is believed to result from declining vaccination rates, despite the availability of highly effective vaccines.
The measles virus is highly contagious, causing fever, watery eyes, and rash when it infects the respiratory system. At its most severe, it can lead to brain damage, blindness, pneumonia, and encephalitis, which can be fatal. According to the latest WHO statistics, over 100,000 people died from measles in 2023, the majority of whom were children. The most susceptible to complications from measles are young children under five years of age, pregnant women, adults over twenty, and those with compromised immune systems.
Vaccination with two doses is recommended to ensure immunity and prevent outbreaks since not all children develop immunity after the first injection. One dose of the measles vaccine is 93% effective, while two doses are 97% effective.
Yet more than 22 million children missed their first dose of measles vaccine in 2023.
Head of Measles and Rubella at Gavi, the Vaccine Alliance, Rebecca Casey, said that gaps in measles vaccination coverage expose millions of children to a preventable disease that still kills hundreds of thousands of people each year. She said such gaps also increase the risk of outbreaks that can overwhelm healthcare systems to the point where essential services cannot be delivered.
"One reassuring finding of the Morbidity and Mortality Weekly Report by the World Health Organization and Centers for Disease Control and Prevention (CDC) is that despite these global challenges, African countries - many of which partner with Gavi for routine immunization - demonstrated resilience and were able to increase vaccine coverage by 2% points to 70% despite a rising birth cohort and competing public health priorities," said Casey.
"Measles, which is one of the leading vaccine-preventable causes of death among children, is highly contagious," she said. "At least 95% vaccination coverage is required to protect children and communities. A single case is enough to lead to an outbreak if there aren't adequate levels of vaccination coverage. This presents a significant challenge to lower-income countries that continue to struggle to reach all children with measles vaccines and close immunity gaps."
A single case of measles can cause an outbreak without adequate vaccination levels, Casey said, which poses a significant challenge to lower-income nations needing to close immunity gaps and ensure that all children receive vaccines.
"To overcome the risk of missed children and reduce dropout between a child's first and second dose, Gavi works with countries to implement catch-up campaigns," she said.
Casey said that because of the "high contagiousness" of measles, they refer to it as a "tracer". When measles cases are identified, it is a sign that the country or region needs to strengthen its routine immunization program. The measles or measles-rubella vaccination campaign serves as an important entry point for routine immunizations and other essential services when an unimmunized child is identified and reached.
Bringing vaccines to the doorstep
Worldwide measles cases pose a risk to all countries and communities with low immunization coverage. In addition to occurring most often in communities that are under or un-vaccinated, outbreaks are indicative of weaknesses and inequities in immunization programs.
Casey said efforts to roll out vaccines must include reaching rural and underserved communities.
"In more complex settings, this calls for innovation to facilitate vaccine delivery and improve community demand and access," she said. "This is why Gavi and the Measles and Rubella Partnership have been looking into innovations such as Microarray patch vaccines (MR-MAPs), which showed promising trial results in 2022, allowing for easier vaccine delivery in hard-to-reach areas without extensive cold chain infrastructure."
Gavi launched a novel type of partnership in 2022 as a result of a focus on innovation
A program called the Zero-Dose Immunization Programme, or ZIP, aimed to reach millions of children in fragile areas of the Sahel and Horn of Africa, who were at the time being completely ignored by health systems. Gavi worked with two consortia of organizations (led by World Vision and International Rescue Committee) who had extensive operational experience in the area, investing U.S.$100 million to find and serve these missing millions.
"Further, Gavi's health system and immunization strengthening support are aimed at enabling countries to build strong, equitable, sustainable, and high-quality systems and to strengthen the management of their programs and vaccines," said Casey. "This is also a key lever in helping countries reach zero-dose children and underserved communities."
Measles fight intensifies in conflict areas
Health systems may not seem to be a priority in a war or conflict zone. According to the WHO, nearly a quarter of the world's population lives in fragile, conflict-affected, and vulnerable regions. More than 70% of epidemic-prone diseases, such as cholera, measles, and meningitis, and half of all deaths in children under five, take place in these countries.
According to Casey, conflict areas present huge challenges to immunization programmes, posing a high risk of health threats, and Gavi is working to address this through multi-faceted strategies that aim to address both immediate and long-term issues.
"This approach includes working in partnership with local governments and humanitarian organizations to ensure that vaccination campaigns are integrated with broader health interventions," she said. "For instance, in Sudan, we are working with organizations like UNICEF and Save the Children to deliver vaccines reaching vulnerable populations in hard-to-reach areas. This allowed the rollout of a campaign amid the ongoing conflict."
Gavi committed U.S.$20 million to ensure that thousands of children in the Gaza Strip, West Bank, and Palestinian refugee camps in Lebanon receive essential vaccinations, and remains committed to strengthening health systems in conflict-affected areas by providing technical assistance and funding for healthcare infrastructure, including training for healthcare and community outreach professionals.
"Through the Measles & Rubella Partnership's Outbreak Response Fund, Gavi is the main funder of measles outbreak response activities in low-income countries, investing more than U.S.$11 million in 2024 in the partnership's Outbreak Response Fund to support outbreak response in six countries," she said.
Vaccine hesitancy
Measles infections can be prevented with vaccines, such as the MMR (measles, mumps, rubella) vaccine, which provides up to 97% protection after two doses. Vaccine hesitancy and misinformation, on the other hand, have fueled the resurgence of measles, placing unvaccinated individuals at heightened risk for infection. According to WHO Director-General Dr. Tedros Adhanom Ghebreyesus, the measles vaccine has saved more lives than any other vaccine over the past 50 years, and to continue saving lives and preventing this deadly virus from harming the most vulnerable, we must invest in immunization for everyone, regardless of where they live.
"Misinformation about vaccines can lead to hesitancy, but hesitancy can also stem from people lacking the right information about a vaccine or its lifesaving benefits. Gavi takes a multi-pronged approach to ensuring information is available in the context of different communities, regions, and countries," said Casey.
She said that Gavi is working with Ministries of Health, UNICEF, WHO, local leaders, healthcare providers, and civil society organizations as part of a broader alliance to address hesitancy, dispel myths, and build public trust in vaccines by conducting public awareness campaigns and engaging community members.
"We are also involved at national and community levels to support adequate community leadership, engagement, and awareness. Parents and caregivers need to hear accurate messages from trusted sources, and the answer as to who that trusted source is can be different in every context ranging from healthcare workers, religious leaders, local leaders, and renowned personalities among others," said Casey. "A big part of any vaccine introduction or campaign factored into the budget that Gavi finances, is training for healthcare workers to be accurate sources of information for parents and caregivers with questions, as well as ensuring other leaders within the community are equipped with the right information as well."
Measles immunization rebooted post-COVID
The number of people getting even standard vaccinations decreased globally since the Covid-19 epidemic. The COVID-19 pandemic led to a setback in surveillance and immunization efforts, according to the WHO. Millions of children have been exposed to preventable diseases such as measles as a result of the suspension of immunization services and declines in immunization rates and surveillance across the globe.
Because of its high transmissibility, measles serves as an early warning system, exposing immunity gaps quickly. The number of children who missed their first dose of measles in 2016 was 22.22 million, far higher than the 19.3 million who missed it in 2019. As of 2023, 83% of children had received one dose of measles-containing vaccine by their second birthday, and 74% had received two doses of measles vaccine.
"Across the world, the pandemic led to a decline in routine immunization including measles vaccination coverage, and achieving high coverage was already challenging before the pandemic," said Casey. "Despite many Gavi-supported countries getting back on track, global measles vaccination coverage remains below the 86% pre-pandemic coverage. To increase coverage further, we continue to work with countries to strengthen health care workforces, improve health service delivery, build trust and demand for vaccines within communities, and address gaps and obstacles to restoring immunization."
This is why Gavi, she said, in partnership with lower-income countries, has committed to strengthening routine immunization by introducing a second dose measles vaccine, as well as implementing timely, high-quality preventive campaigns to further reduce the risk of outbreaks.
Sign up for free AllAfrica Newsletters Get the latest in African news delivered straight to your inbox
Success!Almost finished...
We need to confirm your email address.
To complete the process, please follow the instructions in the email we just sent you.
Error!There was a problem processing your submission. Please try again later.
In the WHO and CDC measles report, she said that African countries increased vaccine coverage by 2% points to 70% in 2023 with the help of Gavi and other partners, despite a rising birth cohort and competing public health priorities.
As of 2024, Gavi is supporting countries in implementing vaccination campaigns in 24 countries to reach over 100 million children. In addition, the Gavi Board approved U.S.$290 million in funding in 2023 for the "Big Catch Up" initiative. This initiative is designed to support countries in closing immunity gaps created by disrupted immunization programs during the COVID-19 pandemic.
Global vision for eradication
Over the past 23 years, Gavi has supported lower-income countries to reach more than 859 million children with measles and measles-rubella through measles and measles-rubella campaigns; more than 437 million with measles follow-up campaigns; and more than 214 million with routine vaccinations.
Casey said that in their current strategic period (2021-2025), the total investment in measles and rubella is U.S.$604 million. The funds enable vaccine procurement and support for routine immunization (including the introduction of a second dose of measles, and rubella vaccines), the implementation of preventive campaigns, and outbreak response through the Measles & Rubella Partnership's Outbreak Response Fund.
For the next strategic period, 2026-2030, Gavi aims to protect more people against a greater variety of diseases, including measles, faster than ever before. Gavi reached 1 billion children (across all antigens) in the first two decades of its existence. Its goal is to reach the next billion in half the time. The ongoing replenishment for the next strategic period is critical to ensuring continued access to vaccines.
"For measles, this translates to maintaining our efforts as well as innovating further to reach more children, everywhere," she said. "This will see more innovation and strategies for easier vaccine delivery in hard-to-reach areas to overcome challenges such as lack of extensive cold chain infrastructure. Efforts will be going into safeguarding funding for measles and rubella follow-up campaigns which will be consolidated into one cash envelope to support the country with advance planning and mitigation of outbreaks.
"The ability to access vaccines for children and all people throughout their life course will help reduce childhood mortality rates, improve health outcomes, and improve the quality of life for communities around the world," she said. In her role as Gavi's Director of Vaccine Programs, Casey is motivated to lead these efforts because of the possibilities they accomplish.
Fact Check: Smallpox Eradicated In 1980, Not Just 'held In Check' By Vaccines
Your browser is not supportedstatesman.Com
statesman.Com wants to ensure the best experience for all of our readers, so we built our site to take advantage of the latest technology, making it faster and easier to use.
Unfortunately, your browser is not supported. Please download one of these browsers for the best experience on statesman.Com
Comments
Post a Comment