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The Case for the Texas Children’s Hospital Center for Vaccine Development COVID-19 Vaccine Technology
Mark A. Wallace, President and CEO, Texas Children’s Hospital
Madison Haynes, Practice Administrator
“The pandemic has reminded us, in the starkest way possible, of the price we pay for weaknesses in health systems, social protections and public services.”
António Guterres, 2020
Nearly three years into the worst pandemic seen in a century, the global economy remains in a state of flux with Russia’s ongoing war of aggression in Ukraine, intensifying energy price shocks, rising inflation, and continuing uncertainty regarding the progression toward epidemiologic and market recoveries. As communities worldwide have been trying to recover from pandemic-related challenges, they are now also contending with global food insecurity and rising fuel prices attributable to global supply chain disruptions. According to some, these issues have now supplanted the pandemic as the primary factors impacting economic performance and stability.
However, with ~200,000 COVID-19-related deaths across the world in the first 4 months of 2023, and the virus retaining its ability to evolve into new variants with unpredictable characteristics, managing and mitigating the devastating impacts of this virus must remain a priority.i By continuing to invest in and strengthen global health security architecture, we can prevent, detect, respond and diminish the impact on both global health and economic losses stemming from future pandemic threats. Additionally, prioritizing our capacity to address future health threats will allow economies to better withstand the impact of ongoing sociopolitical and geopolitical conflicts.
As of May 2023, confirmed global case counts exceed 764 million, and while most of the population in upper-income countries have received complete vaccine dose series and booster shots, vaccinating the rest of the world remains challenging.ii While we have achieved the World Health Organization (WHO) global target of having countries and economies with vaccination rates above 70%, the majority of these are high-income countries. That leaves almost 2.4 billion people who have not received any vaccines, primarily in low and middle-income countries (LMICs) and economies. The uncertainty associated with emerging variants and the lack of equitable access, infrastructure, capacity and health workers to reach those at the highest risk, along with vaccine hesitancy, continue to be the key challenges in vaccinating the rest of the population. As long as large segments of the population remain unvaccinated or without access to booster shots, the risk remains for new variants to emerge, and in our interconnected world, we are only as protected as the least immunized country.
In 2020, the Texas Children’s Center for Vaccine Development (CVD) led by Drs. Maria Elena Bottazzi and Peter Hotez, developed a COVID-19 vaccine technology using a well-established protein sub-unit production platform. Developed by an incredible team of scientists, with an eye towards equity, grounded on a technology with proven safety and efficacy, practical in production and administration, affordable and free of the limits placed by patents and intellectual property protection, the Texas Children's CVD COVID-19 response was a promising and proven large-scale global solution.
The COVID-19 vaccines that resulted from the Texas Children's CVD technology have been proven effective at preventing fatal outcomes against the original Wuhan isolate of SARS-CoV-2 as well as the Alpha, Beta, Delta and Omicron variants. Ahead of the May 18, 2023, World Health Organization COVID-19 Vaccine Composition Advisory Group and the June 15, 2023 FDA Vaccine and Related Biological Products Advisory Committee (VRBPAC)iii announcements, Texas Children's CVD had already developed and transferred the new monovalent vaccine prototype against the XBB strain, which is an ideal strategic option for supporting the global immunization infrastructure.iv
Texas Children's CVD’s vaccine technology has been licensed and co-developed in India alongside Biological E, an India-based biopharmaceutical manufacturer, and branded as CORBEVAXTM, and in Indonesia alongside PT Bio Pharma, an Indonesian state-owned manufacturer, and branded as IndoVacTM. More than 100 million doses of these vaccines have been administered in India and Indonesia, providing proof-of-concept that it is possible to initiate ambitious vaccine development projects from the research arm of the United States-based children and women’s hospital. The Texas Children's CVD vaccine technology continues to be a critical tool in the race to outpace new variants of COVID-19.
In this paper, we present how the Texas Children's CVD COVID-19 vaccine technology could help the United States and the world achieve its key objectives in its ongoing COVID-19 global response and recovery efforts, namely vaccinating the highest risk and hardest to reach populations and preparing for future variants and pandemic threats by strengthening global health security infrastructure.v This includes development and production of new XBB variant-specific booster and a universal coronavirus vaccine.
Globally, the Texas Children's CVD vaccine technology has enabled vaccine manufacturers to seek WHO licensure and pre-qualification, which will expand onward manufacturing and global distribution of the next generation of COVID-19 vaccines. In addition, with additional partnerships within the United States Government (USG) and donor community, this technology can equalize the playing field in emerging markets and help the US mark its place in history in leading global vaccine diplomacy.
The Case for Global Vaccination
COVID-19 impacted economies, global health and national security in ways that may never be accurately quantified. Prior to the availability of treatment and vaccines, containment measures established to mitigate the spread of the virus resulted in unprecedented economic loss across the world. Starting in March 2020, pandemic-related supply demands created downstream impacts on pricing and inflation as lockdowns resulted in factory shutdowns, stopping or delaying production and delivery, resulting in stretched supply chains globally. In the US, supply chain challenges collided with the provision of pandemic-related economic relief funds that yielded increased consumer demand and resulted in unstable market dynamics.
The economy, weakened by the pandemic, has not yet reached a “steady state” that resembles conditions in pre-pandemic times. COVID-19 continues to create economic challenges globally, especially with the emergence of new variants, which periodically create reverberations in the investment markets. We saw it clearly at the end of 2021 with the emergence of the Omicron variant. The potential that other future variants will force more restrictions and shutdowns, constrict an already tight labor market and slow the pace of economic growth remains valid.vi
Today, the economy remains strained with overlapping crises, including the war in Ukraine, which diminished the supply of energy and global commodities like wheat and fertilizer, together with significant disruptions in trade, and the surge in food and fuel prices, all fueling inflation and tightening global financing conditions. Supply constraints, related first to the pandemic and now to the war in Ukraine, together with surging demand and a tight labor market have all contributed to increased financial strains and declines in consumer and business confidence.
To mitigate economic vulnerability, the need for safe and effective, streamlined, low-cost vaccines for LMICs is central to the world’s fight against future COVID-19 threats and in preventing the next pandemic. Without widespread vaccination of populations in these areas, additional virus variants will continue to arise, hindering the progress achieved by currently available vaccines in the United States and other higher income countries. It is imperative to renew efforts in our approach to vaccinating the rest of the global population ahead of the emergence and spread of new COVID-19 variants and outbreaks of other pathogens with pandemic potential.
The Texas Children's CVD COVID-19 Vaccine Technology
The United States has committed to investing in global health security, outlining three objectives in the “US Global Response and Recovery Framework”, published by the Biden administration in September 2022: 1) Vaccinate the highest risk and hardest to reach 2) Scale and integrate testing and treatment and 3) Prepare for future variants and pandemic.vii In an effort to achieve these objectives, a vaccine technology, produced by a preeminent children and women’s hospital based in Houston, Texas, allows a unique opportunity to play a pivotal role in doing so in an efficient, effective and equitable way.
This vaccine technology, developed at the Texas Children’s Center for Vaccine Development, created by a team of scientists led by Drs. Maria Elena Bottazzi and Peter Hotez, is the result of a decade of scientific knowledge that began in 2011, after the SARS coronavirus outbreak. It was created using the same well-established protein sub-unit production platform as the one used to develop the Hepatitis B vaccine, producing proteins via microbial (yeast) fermentation that induce an immune response without causing disease.viii The Texas Children's CVD rapidly adapted and modified the strategy to create a specific vaccine target against COVID-19 and signed a non-exclusive license with Biological E Limited (BioE), a pharmaceutical company based in Hyderabad, India, to develop the first low-cost and affordable COVID-19 vaccine for global access, called CORBEVAXTM. The technology (i.e. cell banks), the recipes and other supporting reagents needed to develop CORBEVAXTM were originally shared with BioE in May of 2020. After completing phase three trials, BioE was granted Emergency Use Authorization (EUA) of CORBEVAXTM by the Drugs Controller General of India in December 2021. The government of India signed an advanced-purchase commitment for 300 million doses and has thus far administered the two-dose regimen to more than 70 million children and adolescents, with an estimated 500,000 doses distributed daily.ix Currently, CORBEVAXTM is also approved as a booster vaccine for individuals previously vaccinated with COVAXINTM and COVISHIELD,TM and more than 10 million boosters have been administered.
In parallel, Texas Children's CVD signed a non-exclusive license with PT BioFarma, a state-owned pharmaceutical company in Indonesia, to develop a “Halal” COVID-19 vaccine for global access. A halal vaccine means it was manufactured in full compliance with Islamic law, containing no components that would be deemed “impure”. Socio-cultural differences and religious beliefs are leading factors contributing to vaccine hesitancy, and the halal certification mitigates this for the Muslim community. In October 2022, the Texas Children's CVD vaccine technology received EUA in Indonesia and was also certified as the first halal COVID-19 vaccine under the name of IndoVacTM. To date, more than 20 million doses have been deployed in Indonesia. Currently, IndoVacTM is also approved as a booster vaccine in individuals previously vaccinated with Pfizer mRNA vaccines and more than 10 million boosters have been administered.
Most recently, the Texas Children's CVD rapidly developed the XBB-based vaccine technology, which could be used as a heterologous booster for other vaccine platforms globally. Furthermore, a universal coronavirus vaccine platform is under development using the same low-cost and patent-free approach that was successfully used to vaccinate India and Indonesia.
Texas Children's CVD’s role in the US Global Response and Recovery Framework
Vaccinate the highest risk and hardest to reach
While the goal to “Vaccinate the highest risk and hardest-to-reach” has been indicated by the USG, with an emphasis on making vaccines more widely available to increase rates of vaccination, increasing the supply is an incomplete solution. Combined with vaccine hesitancy, supply flows overwhelming existing administration capacities and ultra-cold chain requirements have contributed to delayed global vaccination, creating a point of entry for the Texas Children's CVD Vaccine Technology.
With equity and ease of access at the forefront of this development, this Texas-made vaccine technology is nearly 20 times less expensive than current mRNA (messenger RNA) vaccines in the market and far easier to produce and distribute in remote settings, with no ultra-cold refrigeration requirements. Whereas the ultra-cold chain (-70° C) delivery and storage requirements of mRNA vaccines have made it challenging, if not nearly impossible, to deliver and administer stocks of donations ahead of expiration, wasting resources and funding.
Simple enough to deliver in resource-constrained settings due to its uncomplicated cold chain requirements, and safe enough to administer with other vaccines, this vaccine is the most feasible and least expensive option for LMICs to overcome these challenges. In addition, Texas Children's CVD’s technology is transparent, with every step of the design, production process and testing published in open access biomedical literature.
Preparing for future variants and pandemics
The SARS coronavirus, H1N1 influenza and Ebola virus created lasting impacts at the country, regional and global levels, exposing major weaknesses in the global system for addressing epidemic threats, and with the increasing rate of growth and interconnectedness of the global population, it can be predicted that zoonotic diseases and outbreaks will continue to surface. In his recent book, “Preventing the Next Pandemic” (Johns Hopkins University Press), Dr. Peter Hotez, who served as United States Science Envoy for the White House and State Department in 2015 and 2016, stated that viruses are now emerging at an accelerated pace due to the confluence of climate change, rapid urbanization and shifting patterns of human and animal migrations.x Dr. Hotez also noted recently that, “new coronaviruses are jumping from bats to people hundreds or even thousands of times daily. Every few years one catches fire and causes a pandemic. We should expect yet another major and entirely new coronavirus pandemic to strike us before 2030.”xi The Texas Children's CVD vaccine technology is not only a critical tool to global vaccination to avert new variants of COVID-19, but it is also a strategic option for supporting the global immunization infrastructure to prepare for future pandemics, the Response and Recovery Framework’s third objective. The patent-free technology, available to any manufacturer capable of mass producing, creates an opportunity to close the vaccine gaps felt across the world, created by the more expensive, newer vaccine technologies that today are still not able to be quickly scaled for global production.
The current vaccine ecosystem still depends heavily on multinational companies to advance innovations and provide safe and effective vaccines. Texas Children's CVD’s approach provides access to the technology and underlying research, presents a critical step in leveling the existing model of biopharmaceutical engagement and directly supports international cooperation by allowing local scientists a seat at the table; aligning with the USG’s statement to “Invest in and support local and regional supply production and to ensure more diversified manufacturing of and a sustainable market and ecosystem for vaccines and ancillary products.” The US has an opportunity to continue its leadership in global health and vaccine diplomacy by strengthening the biopharma manufacturing capacity of LMICs.
Onward development and distribution will not only support a diversified base of manufacturing partners, but it will also contribute to a more equitable and trusted approach to the development of, and access to, life-saving immunizations.
With partnerships for vaccine research and development, as well as training and capacity-building projects in process or underway in Latin America, Southeast Asia, Africa and the Middle East, the vaccine infrastructure in LMICs is being empowered to develop and test locally made vaccines based on culturally relevant and population-based needs. The Indonesian version of the Texas Children's CVD vaccine technology, IndoVacTM, is a prime example of this after receiving halal certification.
The vaccine inequities seen in the COVID-19 pandemic remind us that advancing promising new vaccine technologies is not sufficient. For example, VSV was effective for the Ebola virus but failed for SARS-CoV-2; similarly, the mRNA approach may or may not be widely successful beyond SARS-CoV-2. It is equally urgent to maintain traditional technologies, ones that are universally trusted, can be easily transferred and scaled up by vaccine producers globally. A study published in January 2023 found that parental hesitancy to vaccinate children younger than 18 years remains high in many high-income countries, including France, Germany, Sweden, the United Kingdom, the United States and South Korea, as well as some LMICs, such as Kenya and Nigeria.xii This recombinant protein-based technology has been used for decades to produce a highly safe and effective recombinant Hepatitis B vaccine for adults and children. The advantages of Texas Children's CVD recombinant protein technology include: affordability, ease of scalability, compatibility with LMIC vaccine producers, widespread acceptance and proven equity and safety profiles. If there was ever a COVID-19 vaccine technology that might triumph over vaccine hesitancy and refusal in some parts of the world, this could be the one.
Scale and integrate testing
While partnerships for vaccine research and development continue to be established, the Texas Children's Hospital and Baylor College of Medicine (BCM) global healthcare network infrastructure can be leveraged to help deploy tests and vaccines and allows for a pathway to engage with local leaders. With our already established in-country public-private partnerships and a direct line of communication with local communities and ministries of health, our network of locally led, managed, and registered independent non-governmental organizations (NGOs) is an immediately available platform. Texas Children's Hospital and BCM partner facilities in Romania, Botswana, Lesotho, Eswatini, Malawi, Tanzania, Uganda, Colombia, and Argentina, can serve as a key asset by which information can be locally disseminated to increase demand, facilitate vaccination, and support data collection and tracking efforts. The Texas Children's CVD will continue to work with the Texas Children's Hospital and BCM global network towards improving the scaling of supply inputs and manufacturing capabilities worldwide with a goal of increasing the efficiency of existing vaccine development capacity, repurposing existing or unused capacity, and adding new capacity.
Additionally, countries are not only COVID-19 under-vaccinated—they are far behind on routine immunizations. WHO and UNICEF recently reported the largest sustained decline in childhood vaccinations in approximately 30 years. With its versatile abilities, the Texas Children's CVD vaccine technology can be a proponent in re-initiating protection for children at risk of other vaccine-preventable diseases, mitigating the decline in routine vaccinations and avoiding the risk of the re-establishment of previously eliminated diseases, continued strains to health systems, and further weakening already challenged economies. Within the foreign assistance architecture and upon the Texas Children's CVD partner manufacturers receiving WHO PQ, the United States Agency for International Development (USAID), GAVI, the Vaccine Alliance and other global agencies could support rollout of their COVID-19 vaccines as part of routine childhood immunization campaigns. Health and Human Services/ Office of Global Affairs (HHS/OGA) can also play a leading role in facilitating ministerial dialogue in countries where the Texas Children's Hospital and Baylor College of Medicine networks are not as established.
US investment in vaccine diplomacy
The pandemic showed us a threat anywhere can quickly become a threat everywhere. This applies to more than just pathogens. Between concurrent outbreaks of infectious diseases, geopolitical instability and a climate crisis that threatens multiple regions at once, the imperative for global health preparedness is greater than ever before. The US has an opportunity to mark its place in history as a critical leader in rescuing and supporting its own, and pulling other economies out of the global decline driven by the COVID-19 pandemic through global vaccine diplomacy. The US can invest in ending the pandemic by funding onward development, production and distribution of the Texas Children's CVD vaccine technologies, but also by facilitating additional partnerships within the government and donor community. Even though CORBEVAXTM and IndoVacTM received no major federal or G7 support, it is notable to highlight the impact of the Texas Children's CVD vaccine technology, with more than 100 million doses administered in India and Indonesia.
The US pledged $4B to COVID-19 Vaccines Global Access (COVAX), and while that funding has supported the delivery and administration of more than 500 million vaccines, inequities remain. With only 40% of people in LMICs having received at least one dose of a COVID-19 vaccine two years into the pandemic, compared to the 77% in higher income countries, the need to support local manufacture, delivery and administration of these vaccines is critical.xiii
The Texas Children's CVD philosophy to develop vaccines that can be rapidly transferrable to LMIC vaccine producers and deployed rapidly to vulnerable populations is the surest way to avoid current and future catastrophic vaccine and health inequities. With additional funding, the Texas Children's CVD can continue with our successful and proven model and establish additional non-exclusive licensing partnerships with other regional or country specific manufacturers. This approach provides economic incentives from manufacturing and sales, and supports vaccine collaborative research through enhanced scientific cooperation. Furthermore, it complements the current model of biopharma manufacture, presenting a sustainable option for localizing vaccine development and manufacturing around the world.
In the launch of the US White House and G7 Build Back Better Worldxiv (B3W) partnership to mobilize private capital for health and health security infrastructure investments, a number of groups were specifically called out as critical partners in the implementation of the global recovery, including: DFC (US International Development Finance Corporation), USAID, MCC (Millennium Challenge Corporation), EXIM (Export Import Bank), and US Trade and Development Agency. The DFC has already played a pivotal role in supporting the manufacture of CORBEVAXTM in India by entering into a $50M agreement for the expansion of Biological E’s vaccine manufacturing facility in Hyderabad, which expanded their capacity to produce COVID-19 vaccines.xv As part of the Quadrilateral Security Dialogue (QSD), commonly known as the Quad, a vaccine partnership was established to help enhance equitable access to safe and effective COVID-19 vaccines in the Indo-Pacific and the world. The partnership demonstrates the USG’s leadership in promoting global health security by developing global, regional and country-level capabilities needed to meet future pandemic threats. Supporting vaccine manufacture in emerging markets not only enables cost-effective and agile country-specific preparedness and response capabilities, but it also protects the global population and economy against future major disruptions in the biopharmaceutical supply chain.
The DFC can continue to promote overseas manufacture, hedging bets in favor of improved bilateral cooperation both commercially and politically for the US. And while considered only in times of humanitarian disaster, the DOD’s capabilities in logistics should not be forgotten. Existing networks of cooperation, both in delivery and in engineering can prove useful in the actual infrastructural development required to promote vaccine manufacture.
Facilitating public–private partnerships across chemical, manufacturing, and control hubs, supply chain actors and national regulatory authorities can support local manufacture of drugs and vaccines and in turn support economic growth, contribute to innovations in treatments and facilitate more agile responses in an outbreak endemic world. Such partnerships should be built and funded so they function in multiple regions and LMICs where almost no vaccine development or manufacturing is currently underway.
Ultimately, vaccine diplomacy requires the balancing of emerging and traditional technologies to achieve our goals of increased access and affordability; safety and efficacy; global production and consistent, trusted quality; collaborative vaccine research; and combatting global anti-vaccine activity. We strive for an ecosystem in which portfolios are aligned, opportunity costs are identified, and development risks are shared and/or reduced. The global COVID-19 vaccine needs are constantly changing with regard to variants of concern, length of immunity, access and availability to children, need for boosters or second-generation vaccines and the development and maintenance of surplus doses.
The Texas Children's CVD COVID-19 vaccine technology is the clearest and most cost-effective option to achieving global vaccination, in that vaccines derived from this flexible and easily replicated formula can be manufactured, delivered and administered at a low cost, in addition to its ease of access. The ability to provide a lifesaving tool and improve global health infrastructure, while bringing about employment opportunities for local manufacturing, makes it a global good without comparison.
viii New COVID vaccine from Texas could be a global game changer : Goats and Soda : NPR
ix https://www.mohfw.gov.in/ x Hotez, P. J. (2021). Preventing the next pandemic: Vaccine diplomacy in a time of anti-science. Johns Hopkins University Press.
xii A survey of COVID-19 vaccine acceptance across 23 countries in 2022