Research Roundup: Breakthrough antibiotic discovery, Rapid Hepatitis B test, New drug delivery method

It is the wish of mothers everywhere to give their babies the healthiest possible start to life. It’s a feeling I remember well as I prepared to give birth to my son Homer amid an active flu and respiratory syncytial virus (RSV) season and a global pandemic—full of hope and full of fear. The first few weeks of a baby’s life are particularly worrisome and nerve-racking for any new parent. That’s because while our little ones are quickly learning to see, grasp, and respond to our voices, it will take up to three months for parts of their still-developing immune systems to mature fully. During this time, they are particularly vulnerable to viruses and bacteria that are an everyday part of life. While my husband and I were lucky to have our son enter this world in a clean and modern hospital and to be able to mostly “bubble” ourselves off from the outside world during those early days, not every parent is so fortunate. It is a well-established reality in global health that a person’s chance of survival is heavily influenced by the circumstances of their birth—including where they are born—but this disparity is especially pronounced in neonatal health.  Each year, more than 2 million babies die in their first month of life and around 2 million more are stillborn—with 98 percent of those deaths occurring in low- and middle-income countries (LMICs). These losses reflect some of the most profound and preventable health inequities globally. The potential of maternal immunization To save more babies during their vulnerable first weeks of life, scientists are increasingly looking to harness the potential of the long-standing approach of maternal immunization in an entirely new way. Pregnant women naturally pass on protective antibodies to their developing babies during pregnancy in a process known as passive immunity. As a result, vaccinating women during pregnancy can not only protect them from dangerous diseases but can also protect their newborns during their first few weeks to months of life. Maternal immunization is not a new concept. Flu vaccines, as well as tetanus, diphtheria, and pertussis (whooping cough), or Tdap, vaccines are given to mothers worldwide as a routine part of prenatal care—I received both in my third trimester—and have proved stunningly successful. Neonatal tetanus deaths worldwide have been reduced by more than 95 percent since the late 1980s thanks, in significant part, to maternal immunization, and maternal pertussis vaccination has been shown to be 95 percent effective in preventing infant deaths from whooping coughMore nascent on the scientific front are efforts to develop vaccines designed specifically for pregnant women for the purpose of maternal immunization.  Historically, research into maternal vaccines has been limited, largely due to concerns about the ethical and safety considerations of studying and administering vaccines during pregnancy.  But thanks to interest and investments from major global health research funders like the Gates Foundation and its efforts to better characterize statistical baselines for “normal” pregnancy outcomes to meaningfully enable comparative research, a small but promising pipeline of new maternal vaccines has emerged. Harnessing maternal vaccines to combat leading causes of infant death The first-to-market new maternal vaccine was an RSV vaccine from Pfizer, which was first approved by the US Food and Drug Administration in August 2023, making it the first and, still, the only available maternal vaccine to protect infants against RSV, a common respiratory disease that claims the lives of 100,000 children under five each year, with half of those deaths occurring before six months of age. The vaccine, which is given to pregnant women between weeks 32 to 36 of pregnancy, helps protect infants during their first six months of life.More recently, the vaccine was recommended and then later prequalified last month by the World Health Organization, which should help support the procurement and uptake of the vaccine worldwide, particularly in LMICs, where the mortality burden of RSV is the greatest.Beyond RSV, maternal vaccines are being advanced against two other infections that are significant drivers of infant deaths worldwide, Group B Streptococcus (GBS) and Escherichia coli. GBS bacteria, if transmitted to an infant during pregnancy or childbirth, can lead to serious and deadly conditions, including meningitis, pneumonia, or sepsis. It’s a common infection: about one in four pregnant women carry it, but the resulting health outcomes for infants are drastically different depending on where in the world one gives birth. In high-income countries, pregnant women are screened for GBS as part of routine prenatal care, and, if infected, they are given antibiotic treatments prior to delivery. In low-income countries, with less capacitated health systems, this care is less likely to occur, leading to a stark difference in health outcomes. An estimated 97 percent of infant GBS deaths are in LMICs.But the future could look brighter. A promising maternal vaccine for GBS from Pfizer completed Phase 2 clinical trials in 2023 and received a breakthrough designation from the US Food and Drug Administration to expedite its development and review. A second vaccine candidate from MinervaX is also in Phase 2 development. Researchers estimate that maternal GBS vaccination could prevent more than 50,000 GBS-related deaths and 170,000 preterm births annually. Similar to GBS, E. coli is a common bacterium, often transmitted from mothers to their babies during childbirth, which can cause serious illnesses, including meningitis and sepsis. Proper screening and antibiotic treatment during pregnancy can greatly reduce these risks, but for those newborns that do develop sepsis, the speed with which treatment is delivered is a key determinant of survival. The risk of death from neonatal sepsis increases by 7.6 percent every hour that treatment is delayed, underscoring the risk for infants in LMICs, who are more often born outside health facilities and far from medical care.GHTC member the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator is supporting the development of GlyProVac’s maternal E. coli vaccine, which is still in the early stages of development but, if proven effective, could one day save the lives of at-risk newborns.Healthy beginnings, hopeful futuresAs a parent, I’ve experienced the fear and feeling of helplessness that often comes with having a sick infant. You snuggle and comfort their fragile bodies, doing what you can—including vaccination when available and accessible—but often, especially in low-resource settings, there is little to do beyond monitoring, waiting, and hoping they get better. I know that if the option existed to get a few additional shots to help protect my baby during those early vulnerable weeks of life, I, and so many mothers worldwide, would joyfully jump at the opportunity. In the years ahead, maternal immunization could play an even greater role in preventing hundreds of thousands of newborn and fetal deaths. By embracing its promise, we can help give babies everywhere a healthy beginning and a hopeful future. 

The World Health Organization’s (WHO’s) prequalification (PQ) program plays a critical role in certifying the quality, safety, and efficacy of medical products to expand access to health technologies in low- and middle-income countries (LMICs). In our PQ Pulse interview series, GHTC speaks with stakeholders involved in the PQ process about persistent challenges within this evolving regulatory ecosystem and potential reforms to promote equitable access to innovative medical products.  Our first guest is Pierre Hugo, Vice President of Market Dynamics and Global Supply Security at the Medicines for Malaria Venture (MMV), a nonprofit product development partnership working to advance accessible medicines to treat, prevent, and eliminate malaria. MMV works end-to-end along the research and development pipeline, developing novel products, engaging with regional regulatory bodies, and supporting local manufacturers.In our interview, which has been lightly edited and condensed below, Pierre discusses MMV’s experience navigating WHO PQ and his hopes for the future of the R&D ecosystem.Can you tell us about MMV and the unique role and perspective it brings to product development?We fill the gap and, by and large, are a risk mitigation tool as one of the product development partnerships, or PDPs, within the malaria space to discover, develop, and deliver malaria products. Regarding access, our key ethos is that no drug is a medicine until it's in the hands of the patient. It's all very good and well developing drugs, but if they aren't developed correctly or affordably for the target population and ultimately made available, it's a dead-end game. So, we try to ensure that in the last mile, or the death-mile, drugs are getting to the patients. WHO PQ and organizations like MMV play a very important role.Broadly speaking, how would you describe MMV's experience with engaging in the WHO PQ process?  We’ve got a number of products that are now WHO prequalified, working with our pharmaceutical partners. We see the whole PQ process as a critical mechanism to ensure that quality standards are adhered to and, ultimately, to make quality-assured products available in LMICs, where maybe those regulatory pathways are a little bit less mature. I think what's great to see is that the landscape is changing, with a lot more countries achieving WHO maturity-level 3 status [Editor note: a WHO designation for countries with stable, well-functioning regulatory systems]. Yes, there have been challenges. WHO has been very collaborative, the team has been engaging, and we are grateful for the support that WHO PQ provides.Looking forward, it's going to be critical to see how WHO PQ needs to evolve and change to further strengthen and work more closely with countries’ regulatory mechanisms or pathways.How do you see the regulatory landscape evolving in the coming years, including the potential role of the African Medicines Agency (AMA) and other regional bodies?  The AMA I think is the future; it's critical that it is a success. There's a fair amount of, I wouldn't say pessimism but [questions about] how long it will take for them to be up and running, simply because they just have so many different countries and regional regulatory systems.By and large, the East African collaborative registration or collaborative processes [The Eastern African collaborative registration process is a regional initiative that aims to facilitate the registration of medicines and medical products through a collaborative process, including joint assessments and mutual recognition of regulatory decisions] have been working to some success. There are other regional harmonization networks, but it takes time, and there is still a lot of work that is needed.How do you view recent reforms made to the PQ program? Overall, we are encouraged to see efforts that enable the fast-tracking of innovative product introduction. The new WHO framework for novel products [a reform implemented in 2024 to initiate parallel, rather than sequential, processes for recommending the use of novel products and evaluating them through PQ] is just entering its pilot phase. The new web portal [an online PQ application platform that will provide real-time information for applicants, regulators, and other stakeholders on the status of products in review] will give us greater transparency. The Coordinated Scientific Advice [a new procedure that allows product developers to engage with WHO early on to better understand the evidence that they will need to generate to support PQ review and generation of policy recommendations] should ensure that later review of the finished product is as streamlined as possible.There also needs to be some thought on how AMA will work with the European Medicines Agency, the US Food and Drug Administration, and WHO PQ to avoid complexity for local manufacturers.  If you had a hypothetical magic wand to wave to influence the program, what changes would you make?Something that is critical is to have clarity on timelines and the interaction between PQ and national regulatory bodies and lessons learned. Ultimately, what is the incentive for a manufacturer to go that extra mile to ensure that a product is quality approved [through PQ]? That's where the funders play a critical role in endorsing and supporting the process. Without that support, if you speak to a lot of the manufacturers, they say, “Well, there's no way I'll be going through the WHO PQ process. It's a major investment, and it's an additional long-term commitment that you need to make as a manufacturer.” So, ensuring that there is coordination between normative bodies, funders, procurement partners, and regulators is critical to ensure fast uptake of innovative products.The dream is to have a lot more quality-approved manufacturers in Africa, where over 95 percent of the patient population is. If you look at our new products coming down the line, like single-dose cures or long-acting injectables, greater upfront alignment is key, between WHO PQ and these stringent regulatory authorities, to offer clearer guidance in terms of what those regulatory expectations are for new products. We need to ensure that global procurement agencies, like the Global Fund to Fight AIDS, Tuberculosis and Malaria, the President’s Malaria Initiative, or UNICEF, are working as closely as possible with AMA and with WHO PQ to ensure the rapid uptake of new qualified drugs.I would love to see harmonization between PQ and national regulatory authorities to fast-track important innovation and ensure that new quality-assured drugs get to market faster.Putting on your advocacy hat, where do we, as an advocacy community, need to put our energy in the next couple of years to make some of those improvements become reality?  To unleash the potential [of PQ], we need to simplify the processes for manufacturers, ensure procurement commitments for a clear return on investment, and provide continuous and sustained funding to support manufacturers to embark on the lengthy quality assurance process. If I look at the manufacturers, we did an extensive exercise with the Africa Centres for Disease Control and Prevention to identify manufacturers throughout the whole continent that would want to take malaria products forward to be WHO PQ’d. We only had about 50 manufacturers that were interested in taking part in this initiative [out of 400], so that's a very low number. I mean, we're talking small molecules, not vaccines, and you've got to ask yourself why? They obviously don't see a need to have products WHO PQ’d, which is, on the one hand, a problem. The Africa Centres for Disease Control and Prevention and MMV and other partners believe that the African manufacturing sector can take its place long term alongside manufacturers from India and China, who today supply the vast majority of public health medicines for malaria on the continent.Big Pharma, if anything, is disinvesting in Africa. So, having those in-Africa partners is critical within the malaria space and, obviously, not just for malaria, but for HIV and tuberculosis and so forth.So, I'm just thinking that if manufacturers are going down the WHO PQ route, it might be a really nice carrot to say, “Look, if you are applying for the WHO PQ process, this is a financial incentive in place.” That could be a really nice carrot to keep the Big Pharma guys in the game.