Tropical Medicine Commons^™

Vaccine Value Profile For Schistosomiasis, Gavin Yamey, Kaci Kennedy Mcdade, Roy M Anderson, Sarah M Bartsch, Maria Elena Bottazzi, David Diemert, Peter J Hotez, Bruce Y Lee, Donald Mcmanus, Adebayo J Molehin, Meta Roestenberg, David Rollinson, Afzal A Siddiqui, Miriam Tendler, Joanne P Webster, Hong You, Raphaël M Zellweger, Caroline Marshall

Faculty, Staff and Students Publications

Schistosomiasis is caused by parasitic flatworms (Schistosoma). The disease in humans can be caused by seven different species of Schistosoma: S. mansoni, S. japonicum, S. haematobium, S. malayensis, S. mekongi, S. guineensis and S. intercalatum, as well as by hybrids between species, including livestock schistosome species. People are infected when exposed to infested water and the parasite larvae penetrate the skin. Poor and rural communities are typically the most affected, and the general population who lives in affected areas and is exposed to contaminated water is at risk. Areas with poor access to safe water and adequate sanitation are also …

Averting Collapse: Reimagining The Ntds Ecosystem Through G20 Health Diplomacy And Science Innovation, Maple Goh, Peter J Hotez

Faculty, Staff and Students Publications

The recent termination of the U.S. Government's neglected topical diseases (NTD) mass treatment program, following similar cuts by the UK, threatens decades of progress. Without a strategic reset, NTDs may re-emerge, exacerbating poverty across Africa and beyond. We call for a broadened donor base and reframing NTD control as a shared global interest, especially as NTDs rise in G20 nations due to climate change and urbanization. This moment demands investment in sustainable tools, like NextGen vaccines and biologics, and greater leadership from G20 countries. While USAID's exit is a setback, opportunities arise for decolonizing global health and fostering new partnerships.

Randomized, Observer-Blind, Controlled Phase 1 Study Of The Safety And Immunogenicity Of The Na-Gst-1/Alhydrogel Hookworm Vaccine With Or Without A Cpg Odn Adjuvant In Hookworm-Naïve Adults, David J Diemert, Maria Zumer, Mark Bova, Christina Gibbs-Tewary, Elissa M Malkin, Doreen Campbell, Lara Hoeweler, Guangzhao Li, Maria Elena Bottazzi, Peter J Hotez, Jeffrey M Bethony

Faculty, Staff and Students Publications

BACKGROUND: Recombinant Necator americanus Glutathione-S-Transferase-1 (Na-GST-1) formulated on Alhydrogel (Na-GST-1/Alhydrogel) is being developed to prevent anemia and other complications of N. americanus infection. Antibodies induced by vaccination with recombinant Na-GST-1 are hypothesized to interfere with the blood digestion pathway of adult hookworms in the host. Phase 1 trials have demonstrated the safety of Na-GST-1 formulated on Alhydrogel, but further optimization of the vaccine adjuvant formulation may improve humoral immune responses, thereby increasing the likelihood of vaccine efficacy.

METHODS: A randomized, observer-blind, dose escalation Phase 1 trial was conducted in 24 healthy, hookworm-naïve adults. In each cohort of 12 participants, 4 …

Vaccine Value Profile For Hookworm, Karl Philipp Puchner, Maria Elena Bottazzi, Victoria Periago, Martin Grobusch, Rick Maizels, James Mccarthy, Bruce Lee, Erika Gaspari, David Diemert, Peter Hotez

Faculty, Staff and Students Publications

Hookworm, a parasitic infection, retains a considerable burden of disease, affecting the most underprivileged segments of the general population in endemic countries and remains one of the leading causes of mild to severe anemia in Low and Middle Income Countries (LMICs), particularly in pregnancy and children under 5. Despite repeated large scale Preventive Chemotherapy (PC) interventions since more than 3 decades, there is broad consensus among scholars that elimination targets set in the newly launched NTD roadmap will require additional tools and interventions. Development of a vaccine could constitute a promising expansion of the existing arsenal against hookworm. Therefore, we …

A Trivalent Protein-Based Pan-Betacoronavirus Vaccine Elicits Cross-Neutralizing Antibodies Against A Panel Of Coronavirus Pseudoviruses, Syamala Rani Thimmiraju, Rakesh Adhikari, Jeanna R Redd, Maria Jose Villar, Jungsoon Lee, Zhuyun Liu, Yi-Lin Chen, Suman Sharma, Amandeep Kaur, Nestor L Uzcategui, Shannon E Ronca, Wen-Hsiang Chen, Jason T Kimata, Bin Zhan, Ulrich Strych, Maria Elena Bottazzi, Peter J Hotez, Jeroen Pollet

Faculty, Staff and Students Publications

The development of broad-spectrum coronavirus vaccines is essential to prepare for future respiratory virus pandemics. We demonstrated broad neutralization by a trivalent subunit vaccine, formulating the receptor-binding domains of SARS-CoV, MERS-CoV, and SARS-CoV-2 XBB.1.5 with Alum and CpG55.2. Vaccinated mice produced cross-neutralizing antibodies against all three human Betacoronaviruses and others currently exclusive to bats, indicating the epitope preservation of the individual antigens during co-formulation and the potential for epitope broadening.

A Journey In Science: Molecular Vaccines For Global Child Health In Troubled Times Of Anti-Science, Peter J Hotez

Faculty, Staff and Students Publications

My scientific life in translational medicine runs in two parallel, yet often converging paths. The first, is four-decade-long commitment to develop new vaccines for parasitic and neglected tropical diseases, as well as pandemic threats. This includes a vaccine for human hookworm infection that I began as an MD-PhD student in New York City in the 1980s, and a new low-cost COVID vaccine that reached almost 100 million people in low- and middle-income countries. Alongside this life in scientific research, is one in public engagement for vaccine and neglected disease diplomacy to ensure that people who live in extreme poverty can …

Optimizing Immunogenicity And Product Presentation Of A Sars-Cov-2 Subunit Vaccine Composition: Effects Of Delivery Route, Heterologous Regimens With Self-Amplifying Rna Vaccines, And Lyophilization, William R Lykins, Jeroen Pollet, Jessica A White, Brian Keegan, Leroy Versteeg, Ulrich Strych, Wen-Hsiang Chen, Raodoh Mohamath, Gabi Ramer-Denisoff, Sierra Reed, Christina Renshaw, Samuel Beaver, Alana Gerhardt, Emily A Voigt, Mark A Tomai, Robert Sitrin, Robert K M Choy, Frederick J Cassels, Peter J Hotez, Maria Elena Bottazzi, Christopher B Fox

Faculty, Staff and Students Publications

INTRODUCTION: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.) route has been shown to improve protective mucosal responses in comparison to intramuscular (i.m.) delivery. As we gain knowledge of the limitations of existing vaccines, it is of interest to understand if changes in product presentation or combinations of multiple vaccine modalities can further improve immunological outcomes.

METHODS: We investigated a commercial-stage SARS-CoV-2 receptor binding domain (RBD) antigen adjuvanted with a clinical-stage TLR-7/8 agonist …

The Zebrafish As A Potential Model For Vaccine And Adjuvant Development, Peter J Hotez, Maria Elena Bottazzi, Nelufa Yesmin Islam, Jungsoon Lee, Jeroen Pollet, Cristina Poveda, Ulrich Strych, Syamala Rani Thimmiraju, Nestor L Uzcategui, Leroy Versteeg, Daniel Gorelick

Faculty, Staff and Students Publications

Introduction: Zebrafishes represent a proven model for human diseases and systems biology, exhibiting physiological and genetic similarities and having innate and adaptive immune systems. However, they are underexplored for human vaccinology, vaccine development, and testing. Here we summarize gaps and challenges.

Areas covered: Zebrafish models have four potential applications: 1) Vaccine safety: The past successes in using zebrafishes to test xenobiotics could extend to vaccine and adjuvant formulations for general safety or target organs due to the zebrafish embryos' optical transparency. 2) Innate immunity: The zebrafish offers refined ways to examine vaccine effects through signaling via Toll-like or NOD-like receptors …

Pseudoviruses, A Safer Toolbox For Vaccine Development Against Enveloped Viruses, Syamala R Thimmiraju, Jason T Kimata, Jeroen Pollet

Faculty, Staff and Students Publications

Introduction: Pseudoviruses are recombinant, replication-incompetent, viral particles designed to mimic the surface characteristics of native enveloped viruses. They are a safer, and cost-effective research alternative to live viruses. With the potential emergence of the next major infectious disease, more vaccine scientists must become familiar with the pseudovirus platform as a vaccine development tool to mitigate future outbreaks.

Areas covered: This review aims at vaccine developers to provide a basic understanding of pseudoviruses, list their production methods, and discuss their utility to assess vaccine efficacy against enveloped viral pathogens. We further illustrate their usefulness as wet-lab simulators for emerging mutant variants, …

Neglected Tropical Disease Vaccines: Hookworm, Leishmaniasis, And Schistosomiasis, Peter J Hotez, Maria Elena Bottazzi, Paul M Kaye, Bruce Y Lee, Karl Philipp Puchner

Faculty, Staff and Students Publications

No abstract provided.

The Impact Of Vaccine-Linked Chemotherapy On Liver Health In A Mouse Model Of Chronic Trypanosoma Cruzi Infection, Duc Minh Nguyen, Cristina Poveda, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez, Kathryn Marie Jones

Faculty, Staff and Students Publications

BACKGROUND: Chagas disease, chronic infection with Trypanosoma cruzi, mainly manifests as cardiac disease. However, the liver is important for both controlling parasite burdens and metabolizing drugs. Notably, high doses of anti-parasitic drug benznidazole (BNZ) causes liver damage. We previously showed that combining low dose BNZ with a prototype therapeutic vaccine is a dose sparing strategy that effectively reduced T. cruzi induced cardiac damage. However, the impact of this treatment on liver health is unknown. Therefore, we evaluated several markers of liver health after treatment with low dose BNZ plus the vaccine therapy in comparison to a curative dose of BNZ. …

Development Of Chimeric Protein As A Multivalent Vaccine For Human Kinetoplastid Infections: Chagas Disease And Leishmaniasis, Marianna De Carvalho Clímaco, Luiza Almeida De Figueiredo, Rayane Cristina Lucas, Guilherme Rafael Gomide Pinheiro, Luísa Mourão Dias Magalhães, Ana Laura Grossi De Oliveira, Raquel Martins Almeida, Fernando Sérgio Barbosa, Daniella Castanheira Bartholomeu, Lilian Lacerda Bueno, Tiago Antonio Mendes, Bin Zhan, Kathryn Marie Jones, Peter Hotez, Maria Elena Bottazzi, Fabrício Marcus Silva Oliveira, Ricardo Toshio Fujiwara

Faculty, Staff and Students Publications

Leishmania spp. and Trypanosoma cruzi are parasitic kinetoplastids of great medical and epidemiological importance since they are responsible for thousands of deaths and disability-adjusted life-years annually, especially in low- and middle-income countries. Despite efforts to minimize their impact, current prevention measures have failed to fully control their spread. There are still no vaccines available. Taking into account the genetic similarity within the Class Kinetoplastida, we selected CD8+ T cell epitopes preserved among Leishmania spp. and T. cruzi to construct a multivalent and broad-spectrum chimeric polyprotein vaccine. In addition to inducing specific IgG production, immunization with the vaccine was able to …

Covid-19 Vaccines And The Pandemic: Lessons Learnt For Other Neglected Diseases And Future Threats, Peter J Hotez, Sarah Gilbert, Melanie Saville, Lois Privor-Dumm, Salim Abdool-Karim, Didi Thompson, Jean-Louis Excler, Jerome H Kim

Faculty, Staff and Students Publications

Through the experiences gained by accelerating new vaccines for both Ebola virus infection and COVID-19 in a public health emergency, vaccine development has benefited from a 'multiple shots on goal' approach to new vaccine targets. This approach embraces simultaneous development of candidates with differing technologies, including, when feasible, vesicular stomatitis virus or adenovirus vectors, messenger RNA (mRNA), whole inactivated virus, nanoparticle and recombinant protein technologies, which led to multiple effective COVID-19 vaccines. The challenge of COVID-19 vaccine inequity, as COVID-19 spread globally, created a situation where cutting-edge mRNA technologies were preferentially supplied by multinational pharmaceutical companies to high-income countries while …

Sars-Cov-2 Variants Offer A Second Chance To Fix Vaccine Inequities, Peter J Hotez

Faculty, Staff and Students Publications

Global COVID-19 vaccine equity remains aspirational for much of the world. But the emergence of rapidly evolving SARS-CoV-2 variants provides new opportunities to correct past public policies, support local vaccine production and combat rising anti-vaccine aggression.

Vaccine-Linked Chemotherapy Improves Cardiac Structure And Function In A Mouse Model Of Chronic Chagas Disease, Kathryn M Jones, Elise N Mangin, Corey L Reynolds, Liliana E Villanueva, Julio Vladimir Cruz, Leroy Versteeg, Brian Keegan, April Kendricks, Jeroen Pollet, Fabian Gusovsky, Maria Elena Bottazzi, Peter J Hotez

Faculty, Staff and Students Publications

INTRODUCTION: Chagas disease, caused by chronic infection with the protozoan parasite Trypanosoma cruzi, affects 6-7 million people worldwide. The major clinical manifestation of Chagas disease is chronic Chagasic cardiomyopathy (CCC), which encompasses a spectrum of symptoms including arrhythmias, hypertrophy, dilated cardiomyopathy, heart failure, and sudden death. Current treatment is limited to two antiparasitic drugs, benznidazole (BNZ) and nifurtimox, but both have limited efficacy to halt the progression of CCC. We developed a vaccine-linked chemotherapy strategy using our vaccine consisting of recombinant Tc24-C4 protein and a TLR-4 agonist adjuvant in a stable squalene emulsion, in combination with low dose benznidazole treatment. …

Editorial: The Regulatory Immune System As A Target To Improve Adjuvants And Novel Vaccines, Carlos Jiménez-Cortegana, Cristina Poveda, Gabriel Cabrera

Faculty, Staff and Students Publications

No abstract provided.

Vaxi-Dl: An Artificial Intelligence-Enabled Platform For Vaccine Development, P Preeti, Swarsat Kaushik Nath, Nevidita Arambam, Trapti Sharma, Priyanka Ray Choudhury, Alakto Choudhury, Vrinda Khanna, Ulrich Strych, Peter J Hotez, Maria Elena Bottazzi, Kamal Rawal

Faculty, Staff and Students Publications

Vaccine development is a complex and long process. It involves several steps, including computational studies, experimental analyses, animal model system studies, and clinical trials. This process can be accelerated by using in silico antigen screening to identify potential vaccine candidates. In this chapter, we describe a deep learning-based technique which utilizes 18 biological and 9154 physicochemical properties of proteins for finding potential vaccine candidates. Using this technique, a new web-based system, named Vaxi-DL, was developed which helped in finding new vaccine candidates from bacteria, protozoa, viruses, and fungi. Vaxi-DL is available at: https://vac.kamalrawal.in/vaxidl/ .