“The Big Catch-Up,” the theme of this year’s World Immunization Week (April 24-30), is both a reference to the state of global immunizations following the acute phase of the COVID-19 pandemic and a call to action.
The annual observance “comes at a critical time” said William J. Moss, MD, MPH, moderator of a recent panel on potentially game-changing vaccine developments in honor of WIW. Because of COVID-19, “[immunization] levels decreased in more than 100 countries with millions of children missing out on lifesaving protection … It’s critical that we restore immunization services.”
The pandemic also made possible the potential for real innovation in terms of the technology, evaluation, and speed with which vaccines come to the market, Moss pointed out.
It’s a good time to take stock. In the webinar, five public health experts presented exciting advances in the world of vaccines—some of which could help facilitate “The Big Catch-Up,” and perhaps even leapfrog the field beyond the previous status quo. These include microarray patches and new advances in much-needed vaccines for malaria, RSV, tuberculosis, and Shigella. There’s also interplay between these advances: As we learned with COVID, breakthroughs in vaccines for one disease can lend knowledge and problem solving to others.
INNOVATION 1: Microarray Patches Could Deliver Vaccines Virtually Anywhere
Microarray patches have “the potential to revolutionize accessibility,” said Birgitte Giersing, PhD, who leads the Vaccine Prioritisation and Platform work within the WHO’s Immunization Department.
In LMICs, which are disproportionately affected by many vaccine-preventable diseases, both cost and logistics present considerable challenges to immunization programs. More than half of the price tag required to vaccinate a child is “generated in the last mile,” Giersing said. That’s due to the costs of shipping and storing vaccines at cold temperatures upon arrival, then the mixing and administration by a registered health professional in a clinical setting. Then there are the logistics of actually getting shots into arms, which can be challenging in remote locations where health care might not be accessible.
Microarray patches, or MAPs, are coin-sized patches covered either with tiny needles coated in dry vaccine that painlessly penetrate the skin or a formula that dissolves when the patch is pressed onto the skin for 2-5 minutes. These patches don’t require cold temperatures, weigh significantly less than vials requiring needles and syringes, don’t require any mixing, and can be given by untrained community health workers in almost any conditions. Plus, there’s a needle-free advantage of painless delivery, upping the odds that people will get all of the vaccinations they need.
Importantly: although MAP vaccines would be more expensive to purchase up front than needle-and-syringe vaccines, said Giersing, the overall price tag would be lowered by eliminating many of the costlier factors of that “last mile.”
There are currently two MAP’s in the market pipeline: one for measles and one for rubella. Two important next steps, Giersing said, are to evaluate where and in what circumstances MAPs would most likely be used—i.e., for routine, seasonal, or other kinds of immunizations and in what countries or settings—and then leverage those use cases to spur commercial partnerships between vaccine manufacturers and MAP developers.
Ultimately, “the public health and socioeconomic impacts of vaccinating groups you couldn’t previously reach” can’t be ignored, said Giersing, and there’s high interest in many lower- and middle-income countries. Ethiopia, for example, is looking for “a full switch from needle-and-syringe for routine immunizations,” and it’s likely other countries may follow suit.
INNOVATION 2: Two Shelf-Stable Malaria Vaccines
Researchers have been trying to develop a malaria vaccine for over 100 years, but “it’s been pretty tough,” said Sir Adrian Hill, director of the Jenner Institute at Oxford University. “You need exceptionally high titers of antibodies to protect against any stage of the parasite’s life cycle,” which is hard to achieve.
Two vaccines are now showing promise, however: RTS,S and R21/Matrix-M, both of which target a specific protein on the malaria parasite. Although both require four doses to achieve the immune response needed to fight off an infection, the vaccines showed efficacy of 67-75% in adults and up to 80% in children aged 5 to 17 months. Both have met safety standards and vaccinated people maintained good antibody levels for more than two years after the primary series.
Even better: RTS,S and R21/MM don’t require sub-zero storage temperatures. R21/MM, in particular, has a long shelf life, comes in a single vial that doesn’t need to be mixed, and can withstand temperatures up to 104°F for two weeks, making it extremely portable in countries where malaria is endemic.
Ghana and Nigeria have both approved the vaccine for use in children aged 5 months to 3 years, and in 2021 the WHO recommended RTS,S to all children under two in sub-Saharan Africa.
INNOVATION 3: RSV Vaccines Could Put a Major Dent in Global Hospitalizations
“2023 is the year of RSV,” Ruth Karron, MD, professor in International Health said, in terms of licensure and, hopefully, deployment of new products.
As we saw this past winter, RSV poses a significant threat to very young children and elderly adults in every country in the world, but the majority of hospitalizations and deaths occur in LMICs where care options may be limited at best and first come, first served at worst.
There are currently three strategies to mitigate RSV:
- Passive immunization, which involves vaccinating pregnant women so they can pass on antibodies to the fetus.
- “Immunization” of infants with a single dose of monoclonal antibodies.
- Live attenuated or mRNA vaccines for infants, toddlers, and older adults.
There are advancements across all three.
The maternal RSVpreF vaccine from Pfizer, which was given to pregnant women at 24-36 weeks’ gestation during Phase III clinical trials, saw 70-80% protection against severe disease for infants up to 6 months after birth.
Two monoclonals, nirsevimab and clesrovimab, in late-stage development show “high efficacy against all endpoints,” Karron said, which includes lower-respiratory tract infections, hospitalizations, and deaths. Both have been submitted to the FDA, and it’s anticipated that the new products will be on the market by the end of 2023.
Several vaccine candidates for the young and elderly passed Phase 3 clinical trials, and two have applied for licensure from the FDA which has already given favorable reviews.
But there are challenges with uptake to consider: Maternal vaccination rates in the U.S. for flu and TDAP are already abysmal, so it’s unclear what the demand would be for an RSV vaccine. Deployment strategies could get more bang for the buck by targeting countries where there are often severe shortages of hospital beds for children during RSV/respiratory virus seasons.
INNOVATION FOUR: A Slow Process for a New TB Vaccine Creates Opportunities to Build Demand Ahead of Time
The WHO’s End TB Strategy calls for reducing new cases by 80% and deaths by 90% before 2030, said Rupali Limaye, PhD, MPH, an associate scientist in International Health with joint appointments in Health, Behavior and Society and Epidemiology. If there’s not enough investment in new treatments and vaccines to meet these targets, she said, we could see 43 million people develop TB and 6.6 million die by then, totaling $1 trillion in economic costs.
There’s currently one TB vaccine on the market—bacile Calmette-Guerin, or BCG—a live, attenuated (weakened) vaccine with so-so efficacy (18% against infection, and a 75% reduction in deaths but only through age 15) and limited use, as it’s not safe for those with HIV—a key population of people at risk of TB.
A lackluster vaccine won’t move the needle towards ending TB but there are significant challenges inherent to cooking up a new TB vaccine. One is that there’s limited knowledge about the human protective immune response to TB. Another is a lack of animal models that can accurately predict how humans may respond, which significantly hampers a critical step in vaccine development. Other challenges include a lack of clear correlates that relate to protection (for example, the presence of a specific titer in the blood that can indicate higher immunity levels), the need for large and expensive trials to do all of this work, and a disproportionate lack of funding priority from international groups despite TB’s incredible burden.
A TB vaccine pipeline with several candidates in Phase III clinical trials does exist. That process is slow and it’s unlikely we’ll see a new TB vaccine brought to market this year, Limaye said, but this offers another opportunity to start building demand.
“Vaccines do not save lives, vaccinations do,” Limaye said, and now is an opportune time to restore trust in vaccines and apply lessons learned from the COVID-19 vaccine rollouts during the pandemic. While waiting for a TB vaccine to come to market, there’s time to collect and evaluate data around misinformation, mistrust in science, and look at what makes for successful vaccine campaigns.
“Behavioral and social data collection is important to help prepare countries so once a vaccine is available people are interested in/able to access it.”
INNOVATION FIVE: Considering Dual Markets for Shigella Vaccines
Shigella is the second leading cause of diarrheal deaths worldwide and the most common bacterial cause of moderate-to-severe diarrhea in children under 5, said Kawsar Talaat, MD, an associate professor in International Health and co-director of clinical research at the Johns Hopkins Institute for Vaccine Safety. In addition to huge numbers of infections in children in LMICs, Shigella infects travelers and is “a significant antimicrobial threat” all over the world, making it an excellent candidate for vaccine development.
It’s been nearly 100 years since the first attempts at Shigella vaccines. A few things have stood in the way: first, the fact that Shigella vaccines must be “quadvalent,” or containing four different serotypes in order to protect against the majority of strains. Second, oral vaccines showed less efficacy in LMICs so needle-and-syringe vaccines would most likely be needed. Finally, many attempts have resulted in vaccines that cause too many side effects or aren’t effective, so there’s little incentive for manufacturers to invest time or money in creating a low-cost vaccine.
But there are some potential solutions, Talaat said. First, presenting a “dual market” for the vaccines to include children in LMICs and travelers from higher-income countries to those same LMICs. Travelers could pay more for the vaccine which might offset costs for children. Another idea is to create a combination vaccine that protects against other diarrheal diseases that could work for both populations in a dual-market solution.
With these in mind, Talaat said, there are some promising candidates in clinical trials and she hopes there will be something brought to market in the next five to 10 years.
Bottom Line: Vaccine Innovations Save Lives
New methods of delivery, shelf-stable formulas, consideration of benefits of a vaccine campaign beyond preventing disease in an individual, creating robust communications to build vaccine demand, and tapping into new and innovative markets can all build global momentum towards better immunization coverage.
“We’re looking towards the future where we can protect millions of more lives from malaria, TB, RSV, and Shigella,” Moss concluded.
Lindsay Smith Rogers, MA, is the producer of the Public Health On Call podcast, an editor for Expert Insights, and the director of content strategy for the Johns Hopkins Bloomberg School of Public Health.
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