Search

Background: The antigen Na-GST-1, expressed by the hookworm Necator americanus, plays crucial biochemical roles in parasite survival. This study explores the development of mRNA vaccine candidates based on Na-GST-1, building on the success of recombinant Na-GST-1 (rNa-GST-1) protein, currently assessed as a subunit vaccine candidate, which has shown promise in preclinical and clinical studies., Methodology/findings: By leveraging the flexible design of RNA vaccines and protein intracellular trafficking signal sequences, we developed three variants of Na-GST-1 as native (cytosolic), secretory, and plasma membrane-anchored (PM) antigens. After one immunization in mice, mRNA vaccines induced an earlier onset of antigen-specific antibodies compared to rNa-GST-1. Following two immunizations, mRNA vaccines induced similar or superior levels of antigen-specific antibodies compared to rNa-GST-1. Secretory Na-GST-1 was comparable to rNa-GST1 in producing neutralizing antibodies against Na-GST-1's thiol transferase activity, while native Na-GST-1 induced a more robust CD8+ T cell response due to its intracellular accumulation. Although PM Na-GST-1 elicited one of highest titers of antigen-specific antibody and a diverse set of memory T-cell populations, it resulted in a lower ratio of neutralizing antibodies after IgG purification compared to the other vaccine candidates., Conclusions/significance: These findings emphasize the importance of antigen localization in tailoring immune responses and suggest that extracellular antigens are more effective for inducing humoral responses, whereas cytosolic antigen accumulation enhances MHC-1 peptide presentation. Future studies will determine if these in vitro and immunogenicity findings translate to in vivo efficacy. Altogether, mRNA vaccines offer numerous possibilities in the development of multivalent vaccines with single or multiple antigens., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: Maria Elena Bottazzi and Peter Hotez are patentholders and inventors on various vaccines against hookworm., (Copyright: © 2025 De Oliveira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Competing Interests: Peter Hotez is a co-inventor on non-revenue generating patents for neglected tropical diseases owned by Baylor College of Medicine (BCM). He is also a co-inventor of a COVID-19 recombinant protein vaccine technology owned by BCM that was recently licensed by Baylor Ventures non-exclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. These include Biological E (India), BioFarma (Indonesia), Incepta (Bangladesh) and ImmunityBio (United States with partnerships is the African Continent including Botswana and South Africa). The co-inventors have no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries and that result in a commercial license, a share of any royalty income. Any such distribution will be undertaken in accordance with BCM policy.

Background: Endemic in more than 20 countries, Chagas disease affects 6.3 million people worldwide, leading to 28,000 new infections and 7700 deaths each year. Previous meta-analyses on antiparasitic treatment need updates to encompass recent studies and to assess key clinically meaningful endpoints. This study aims to evaluate the impact of antitrypanosomal therapy in preventing or reducing disease progression and mortality in chronic Chagas disease., Methods: We performed a systematic review and meta-analysis of studies reporting the cardiovascular outcomes of antitrypanosomal therapy in patients with chronic Chagas disease. We searched Ovid Embase, Ovid MEDLINE, Ovid Global Health, Scopus, Web of Science Core Collection, Cochrane Library, PubMed, Google Scholar, and Virtual Health Library databases from inception to May 18, 2024. We included aggregated data from randomized controlled studies and observational reports (full articles and abstracts) featuring antiparasitic interventions with benznidazole or nifurtimox compared to a control group. Primary outcomes were electrocardiogram (ECG) changes, disease progression, cardiovascular death, and overall mortality. A customized risk of bias scale assessed the methodological quality of studies, and a random-effects model estimated the pooled risk ratios. This investigation was registered in PROSPERO (CRD42023495755)., Findings: Out of 4666 reports screened, 23 met the pre-specified inclusion criteria (8972 participants). Compared to no treatment or placebo, antiparasitic treatment led to a reduction in i) ECG changes (17 studies, 4994 participants: risk ratio (RR): 0.48, 95% CI 0.36-0.66, p < 0.001; I  = 76.4%) with a number needed to treat (NNT) of 5; ii) disease progression (12 studies, 5722 participants: RR: 0.35, 95% CI 0.23-0.51, p < 0.001; 2  = 72.4%) NNT of 6; iii) cardiovascular death (7 studies, 5662 participants: RR: 0.44, 95% CI 0.21-0.95, p = 0.04; I  = 50.5%) NNT of 22; and iv) overall mortality (10 studies, 7694 participants: RR: 0.54, 95% CI 0.34-0.87, p < 0.001; 2  = 72.4%) NNT of 6; iii) cardiovascular death (7 studies, 5662 participants: RR: 0.44, 95% CI 0.21-0.95, p = 0.04; I 2  = 50.5%) NNT of 22; and iv) overall mortality (10 studies, 7694 participants: RR: 0.54, 95% CI 0.34-0.87, p < 0.001; I 2  = 60%) NNT of 23., Interpretation: We found compelling evidence that antiparasitic treatment significantly reduces the risk of ECG changes, disease progression, cardiovascular death, and overall mortality in chronic Chagas disease. Although the quality of evidence ranges from low to intermediate, with considerable heterogeneity across studies, the potential benefits are substantial. These findings support the broader use of trypanocidal therapy in the management of Chagas disease, though further research remains necessary., Funding: This study had no funding source., Competing Interests: Maria Elena Bottazzi and Peter Hotez are part of a team of scientists advancing research toward the development of a therapeutic Chagas disease vaccine and are listed among the inventors on a Chagas disease vaccine patent submitted by Baylor College of Medicine. Dr. Andres F. Henao-Martinez received educational funds from F2G: Novel Therapeutics for Rare Fungal Infections; and support to attend 3ra Jornada Internacional de Enfermedades Infecciosas y Tropicales as a lecturer in Lima, Peru., (© 2024 The Author(s).)

Trypanosoma cruzi is a protozoan parasite that causes Chagas disease. Globally 6 to 7 million people are infected by this parasite of which 20-30% will progress to develop Chronic Chagasic Cardiomyopathy (CCC). Despite its high disease burden, no clinically approved vaccine exists for the prevention or treatment of CCC. Developing vaccines that can stimulate T. cruzi-specific CD8+ cytotoxic T cells and eliminate infected cells requires targeting parasitic antigens presented on major histocompatibility complex-I (MHC-I) molecules. We utilized mass spectrometry-based immunopeptidomics to investigate which parasitic peptides are displayed on MHC-I of T. cruzi infected cells. Through duplicate experiments, we identified an array of unique peptides that could be traced back to 17 distinct T. cruzi proteins. Notably, six peptides were derived from Tcj2, a trypanosome chaperone protein and member of the DnaJ (heat shock protein 40) family, showcasing its potential as a viable candidate vaccine antigen with cytotoxic T cell inducing capacity. Upon testing Tcj2 as an mRNA vaccine candidate in mice, we observed a strong memory cytotoxic CD8+ T cell response along with a Th1-skewed humoral antibody response. In vitro co-cultures of T. cruzi infected cells with splenocytes of Tcj2-immunized mice restricted the replication of T. cruzi, demonstrating the protective potential of Tcj2 as a vaccine target. Moreover, antisera from Tcj2-vaccinated mice displayed no cross-reactivity with DnaJ in lysates from mouse and human indicating a decreased likelihood of triggering autoimmune reactions. Our findings highlight how immunopeptidomics can identify new vaccine targets for Chagas disease, with Tcj2 emerging as a promising new mRNA vaccine candidate., Competing Interests: LV, RA, JL, JW, NI, BK, MJV, CP, KJ, MEB, PH and JP collaborated in the development of Tc24-C4, a vaccine candidate against Chagas Disease that is currently undergoing clinical evaluation. JP, MEB and PH are listed among the inventors on a Chagas disease vaccine patent, submitted by Baylor College of Medicine., (Copyright: © 2024 Versteeg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: This study aims to understand factors contributing to pediatric COVID-19 vaccine hesitancy among pregnant and postpartum adults., Method: The study used targeted intercept advertising on Facebook, Twitter, and Instagram to recruit a panel of 3600 pregnant and postpartum US adults. Data were collected between December 2021 and April 2022 (i.e., before the introduction of pediatric COVID-19 vaccines in the U.S.). We used logistic regression to understand factors associated with pregnant and postpartum women's hesitancy towards getting children <5 vaccinated against COVID-19. Poststratification weights were applied to analyses to promote the representativeness of the sample. We also conducted a qualitative thematic analysis to determine the reasons for pediatric vaccine hesitancy., Results: Nearly half (45.6 %) of pregnant or postpartum women were hesitant to vaccinate their child against COVID-19. Vaccine hesitancy was lower among those who had a high perceived susceptibility to COVID-19, had increased perceived severity of COVID-19, and increased perceived benefits of the COVID-19 vaccine. Perceived barriers related to long-term side effects of vaccines were positively associated with hesitancy to vaccinate children. Older women, women in urban areas, and those born outside the US were less likely to be hesitant to vaccinate children <5 against COVID-19. Compared to respondents with a high school education or less, the odds of pediatric vaccine hesitancy were higher among respondents with some college. Pregnant and postpartum women who were hesitant about getting children <5 vaccinated cited the following reasons for hesitancy: concerns about the vaccine, lack of evidence on vaccine safety, and the COVID-19 vaccine is not necessary for children., Conclusion: Our findings suggest that public health messages to promote the COVID-19 vaccine for young children should focus on the risks and consequences of the disease and share data on the effectiveness of the vaccine in preventing severe COVID-19-related outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

The central tenets of international scientific collaborations leading to the development, testing, and the equitable distribution vaccines to combat poliomyelitis, smallpox, COVID-19, and other devasting infections, first accelerated in the mid-twentieth century. The genesis of vaccine science diplomacy also coincides with the publication of Le Phénomène Humain ( The Phenomenon of Man ) shortly after the death of its author, the French Jesuit priest and scientist, Dr. Teilhard de Jardin. Several tenets of Teilhard's posthumous essay, including our collective consciousness, and the "conjugated faces" of science and religion, are relevant to a modern vaccine diplomacy framework, even if Teilhard may not have specifically addressed vaccines in his writings. This could also include the potential for arriving at an "omega point" through international scientific collaboration and joint vaccine development, while simultaneously avoiding the destructive forces of anti-vaccine or anti-science activism. Collaborations between the Vatican, Catholic research universities and institutions; and leaders of the Catholic-majority nations in Africa, Asia, and Latin America in an integrated framework might accelerate these activities as they apply to both pandemic threats and neglected diseases of poverty., Competing Interests: The team of scientists at Texas Children’s Hospital Center for Vaccine Development including its co-director Professor Peter Hotez are co-inventors on non-revenue generating patents for neglected tropical diseases owned by Baylor College of Medicine (BCM). They are also co-inventors of a COVID-19 recombinant protein vaccine technology owned by BCM that was recently licensed by Baylor Ventures non-exclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. These include Biological E (India), BioFarma (Indonesia), Incepta (Bangladesh) and ImmunityBio (United States with partnerships is the African Continent including Botswana and South Africa). The co-inventors have no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries and that result in a commercial license, a share of any royalty income. Any such distribution will be undertaken in accordance with BCM policy. In addition, Dr. Hotez is also the author of several books published by academic presses (ASM-Wiley) and Johns Hopkins University Press, and he receives modest royalty income from this activity., (© The Author(s) 2024.)

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 have evaluated the biological and implementation feasibility of the vaccine development as well as the added value of such a novel tool. Based on pipeline landscaping and the current knowledge on key biological aspects of the pathogen and its interactions with the host, we found biological feasibility of development of a hookworm vaccine to be moderate. Also, our analysis on manufacturing and regulatory issues as well as potential uptake yielded moderate implementation feasibility. Modelling studies suggest a that introduction of a vaccine in parallel with ongoing integrated interventions (PC, WASH, shoe campaigns), could substantially reduce burden of disease in a cost - saving mode. Finally a set of actions are recommended that might impact positively the likelihood of timely development and introduction of a hookworm vaccine., Competing Interests: Declaration of Competing Interest The team of scientists at Texas Children’s Hospital Center for Vaccine Development including its co-directors, Professors Peter Hotez and Maria Elena Bottazzi, are co-inventors of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was recently licensed by BCM non-exclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. The co-inventors have no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries that result in a commercial license, a share of any royalty income. To date, BCM has not distributed any royalty income to the co-inventors on the COVID-19 recombinant protein vaccine technology. Any such distribution will be undertaken in accordance with BCM policy. Additionally, professors Hotez and Bottazzi are inventors and patentholders on vaccines against hookworm, schistosomiasis, Chagas disease, and other neglected diseases which are currently in development or in clinical trials. The other authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Competing Interests: We declare no competing interests.

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 significantly reduce parasite burden in the colon, liver and skin lesions from T. cruzi, L. infantum and L. mexicana challenged mice, respectively. These findings were supported by histopathological analysis, which revealed decreased inflammation in the colon, a reduced number of degenerated hepatocytes and an increased proliferation of connective tissue in the skin lesions of the corresponding T. cruzi, L. infantum and L. mexicana vaccinated and challenged mice. Collectively, our results support the protective effect of a polyprotein vaccine approach and further studies will elucidate the immune profile associated with this protection. Noteworthy, our results act as conceptual proof that a single multi-kinetoplastida vaccine can be used effectively to control different infectious etiologies, which in turn can have a profound impact on the development of a new generation of vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The COVID-19 pandemic has disproportionately impacted immunocompromised patients. This diverse group is at increased risk for impaired vaccine responses, progression to severe disease, prolonged hospitalizations and deaths. At particular risk are people with deficiencies in lymphocyte number or function such as transplant recipients and those with hematologic malignancies. Such patients' immune responses to vaccination and infection are frequently impaired leaving them more vulnerable to prolonged high viral loads and severe complications of COVID-19. Those in turn, have implications for disease progression and persistence, development of immune escape variants and transmission of infection. Data to guide vaccination and treatment approaches in immunocompromised people are generally lacking and extrapolated from other populations. The large clinical trials leading to authorisation and approval of SARS-CoV-2 vaccines and therapeutics included very few immunocompromised participants. While experience is accumulating, studies focused on the special circumstances of immunocompromised patients are needed to inform prevention and treatment approaches., Competing Interests: The authors report the following potential competing interests: PH and MEB are co-inventors of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was licensed by BCM non-exclusively and with no patent restrictions to several companies committed to advancing vaccines for low- and middle-income countries. The co-inventors have no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries that result in a commercial license, a share of any royalty income. To date, BCM has not distributed any royalty income to the co-inventors on the COVID-19 recombinant protein vaccine technology. Any such distribution will be undertaken in accordance with BCM policy. MH is Founder and Managing Director of SaudiVax. GK is a member of the WHO SAGE Working Group on COVID-19 vaccines. GK is independent director appointed by the Wellcome Trust, MSD Wellcome Trust Hilleman Laboratories Private Limited and Vice Chair of the Board, Coalition of Epidemic Preparedness Innovations (CEPI). HL reports grants and honoraria from GlaxoSmithKline for training talks and from Merck as a member of the Merck Vaccine Confidence Advisory Board, grants from J&J outside the submitted work. AWS serves as Consultant to WHO. The views presented here reflect her views and not necessarily those of WHO. TS reports grants from National Institute of Allergy and Infectious Disease and Fast Grants and research contracts from GlaxoSmithKline, and ViiV Healthcare. SS reports grants or contracts made to institution from U.S. Department of Defense (Joint Program Executive Office for Chemical, Biological, Radiological and Nuclear Defense), Defense Health Agency, Shionogi, Shire, Ansun, Cidara, Zeteo Tech Inc., F2G, Emergent Biosolutions, Bloomberg Philanthropies, the State of Maryland, NIH National Center for Advancing Translational Sciences, Mental Wellness Foundation, Moriah Fund, Octopharma, Shear Family Foundation, HealthNetwork Foundation, Mayo Clinic, University of Nebraska; consulting fees made directly to author from Immunome, Adagio Therapeutics, Celltrion Healthcare, Karius; payment or honoraria to author for lectures, presentations, speakers bureaus, manuscript writing or educational events from Prime Inc. and Peerview; travel support from Peerview for American Transplant Congress 2022, from NCCN for NCCN Guideline meeting, and from ACP for ACP board of governors meeting; paid participation on a Data Safety Monitoring Board or Advisory Board for Intermountain Health, Karyopharm, Adamis Health; a role on guideline panels for NCCN, IDSA, MSG/EORTC, on RSV vaccine workgroup for ACIP/CDC, as Governor of Washington DC Chapter of ACP, and as member of Board of Governors of ACP; stock or stock options from Immunome. JHK reports personal fees from SK biosciences. CB, YBA, OE, BL, DN, NSW, SOS, and PY declare no conflict of interests. The authors views and opinions in the Review do not necessarily represent the views, decisions, or policies of the institutions, universities, or health systems with which they are affiliated., (© 2023 The Author(s).)

Competing Interests: PJH is a co-inventor of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was recently licensed by BCM non-exclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. He has no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries that result in a commercial license, a share of any royalty income. To date, BCM has not distributed any royalty income to the co-inventors on the COVID-19 recombinant protein vaccine technology. Any such distribution will be undertaken in accordance with BCM policy.

Post-infectious conditions, where clinical symptoms fail to resolve even after pathogen clearance, present major health burdens. However, the mechanisms involved remain poorly understood. In Chagas disease (CD), caused by the parasite Trypanosoma cruzi , antiparasitic agents can clear T. cruzi but late-stage treatment does not improve clinical cardiac outcomes. In this study, we revealed differential metabolic trajectories of cardiac regions during T. cruzi infection, matching sites of clinical symptoms. Incomplete, region-specific, cardiac metabolic restoration was observed in animals treated with the antiparasitic benznidazole, even though parasites were successfully cleared. In contrast, superior metabolic restoration was observed for a combination treatment of reduced-dose benznidazole plus an immunotherapy (Tc24-C4 T. cruzi flagellar protein and TLR4 agonist adjuvant), even though parasite burden reduction was lower. Overall, these results provide a mechanism to explain prior clinical treatment failures in CD and to test novel candidate treatment regimens. More broadly, our results demonstrate a link between persistent metabolic perturbation and post-infectious conditions, with broad implications for our understanding of post-infectious disease sequelae., Competing Interests: Additional Declarations: Yes there is potential Competing Interest. KMJ, ALK, ACL, JP, MEB, PJH and FG currently are involved in a Chagas vaccine development program. MEB and PJH are listed among the inventors on a Chagas disease vaccine patent, submitted by Baylor College of Medicine. FG is employed at Eisai Inc.

Recent surges in antivaccine activism and other antiscience trends now converge with rising antisemitism. During the COVID-19 pandemic, authoritarian elements from the far right in North America and Europe often invoked Nazi imagery to describe vaccinations or at times even blame the Jewish people for COVID-19 origins and vaccine profiteering. Such tropes represent throwbacks to the 14th century, when European Jews were persecuted during the time of the bubonic plague. This article provides both historical and recent perspectives on the links between antiscience and antisemitism, together with the author's personal experience as a Jewish vaccine scientist targeted by both dark forces. New approaches to uncoupling antisemitism from antiscience, while combating both, are essential for saving lives and preserving democratic values.

Pancreatic ACE2 receptor expression, together with increased prevalence of insulin-requiring hyperglycemia in patients with coronavirus disease 2019 (COVID-19), suggested that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pancreatic infection might trigger a β-cell-selective inflammation precipitating autoimmune type 1 diabetes (T1D). We examined T1D incidence in patients with COVID-19 inside a large, global population using a "big data" approach. The incidence in 0-30-year-old patients with confirmed COVID-19 over an ∼15-month period from the beginning of the COVID-19 pandemic was compared with an age-matched population without COVID-19 inside the TriNetX COVID-19 Research Network (>80 million deidentified patient electronic medical records globally). The cohorts were used to generate outcomes of T1D postindex. In those up to 18 years of age, the incidence of insulin-requiring diabetes that could represent T1D in patients with already diagnosed, confirmed COVID-19 was statistically indistinguishable from the control population without COVID-19. In contrast, in those aged 19-30 years, the incidence was statistically greater. These data suggest that the incidence of T1D among patients with COVID-19 <30 years of age, at least up to this time since the beginning of the pandemic, is not greater when compared with an age-, sex-, and BMI-matched population without COVID-19. Nevertheless, we caution that patients with COVID-19 could be asymptomatic of a diabetic/prediabetic state and therefore would not be expected to come to medical attention, remaining undiagnosed. Hence, it is still possible that asymptomatic virus-infected individuals could acquire β-cell autoimmunity, eventually progressing to dysglycemia and clinical T1D at higher rates., (© 2022 by the American Diabetes Association.)

Background: The Necator americanus hemoglobinase, aspartic protease-1 (Na-APR-1), facilitates the ability of adult hookworms to parasitize the intestine of their human hosts. A recombinant version of APR-1 protected laboratory animals against hookworm infection by inducing neutralizing antibodies that block the protein's enzymatic activity and thereby impair blood feeding. A catalytically inactive version of the wild-type hemoglobinase (Na-APR-1(M74)) was expressed by infiltrating Nicotiana benthamiana tobacco plants with an Agrobacterium tumefaciens strain engineered to express the vaccine antigen, which was adjuvanted with aluminum hydroxide adjuvant (Alhydrogel)., Methods: An open-label dose-escalation Phase 1 clinical trial was conducted in 40 healthy, hookworm-naïve adult volunteers in the United States. Participants received 30 or 100 µg of recombinant Na-APR-1(M74) with Alhydrogel or with Alhydrogel co-administered with one of two doses (2.5 or 5.0 µg) of an aqueous formulation of Glucopyranosyl Lipid A (GLA-AF). Intramuscular injections of study vaccine were administered on days 0, 56, and 112., Results: Na-APR-1(M74)/Alhydrogel was well-tolerated; the most frequent adverse events were mild or moderate injection site tenderness and pain, and mild or moderate nausea and headache. No serious adverse events or adverse events of special interest related to vaccination were observed. Significantly higher levels of antigen-specific IgG antibodies were induced in those who received 100 µg Na-APR-1(M74) than those who received 30 µg of antigen. Adding GLA-AF to Na-APR-1(M74)/Alhydrogel resulted in higher levels of IgG against Na-APR-1(M74) in both the 30 and 100 µg Na-APR-1(M74) groups in comparison to the non-GLA formulations at the same antigen dose., Conclusions: Vaccination of hookworm-naïve adults with recombinant Na-APR-1(M74) was well-tolerated, safe, and induced significant IgG responses against the vaccine antigen Na-APR-1(M74). Given these favorable results, clinical trials of this product were initiated in hookworm-endemic areas of Gabon and Brazil., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: David Diemert has patent Multivalent Antihelminthic Vaccine issued to The Albert B. Sabin Vaccine Institute, The George Washington University, The Council of the Queensland Institute of Medical Research. Peter J. Hotez has patent Multivalent Antihelminthic Vaccine issued to The Albert B. Sabin Vaccine Institute, The George Washington University, The Council of the Queensland Institute of Medical Research. Jeffrey Bethony has patent Multivalent Antihelminthic Vaccine issued to The Albert B. Sabin Vaccine Institute, The George Washington University, The Council of the Queensland Institute of Medical Research. Maria Elena Bottazzi has patent Multivalent Antihelminthic Vaccine issued to The Albert B. Sabin Vaccine Institute, The George Washington University, The Council of the Queensland Institute of Medical Research. Peter J. Hotez has patent Human Hookworm Vaccine issued to The George Washington University. Maria Elena Bottazzi has patent Human Hookworm Vaccine issued to The George Washington University. Jeffrey Bethony has patent Human Hookworm Vaccine pending to The George Washington University., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Chagas disease (CD) is caused by Trypanosoma cruzi and affects 6-7 million people worldwide. Approximately 30% of chronic patients develop chronic chagasic cardiomyopathy (CCC) after decades. Benznidazole (BNZ), one of the first-line chemotherapy used for CD, induces toxicity and fails to halt the progression of CCC in chronic patients. The recombinant parasite-derived antigens, including Tc24, Tc24-C4, TSA-1, and TSA-1-C4 with Toll-like receptor 4 (TLR-4) agonist-adjuvants reduce cardiac parasite burdens, heart inflammation, and fibrosis, leading us to envision their use as immunotherapy together with BNZ. Given genetic immunization (DNA vaccines) encoding Tc24 and TSA-1 induce protective immunity in mice and dogs, we propose that immunization with the corresponding recombinant proteins offers an alternative and feasible strategy to develop these antigens as a bivalent human vaccine. We hypothesized that a low dose of BNZ in combination with a therapeutic vaccine (TSA-1-C4 and Tc24-C4 antigens formulated with a synthetic TLR-4 agonist-adjuvant, E6020-SE) given during early chronic infection, could prevent cardiac disease progression and provide antigen-specific T cell immunity., Methodology/ Principal Findings: We evaluated the therapeutic vaccine candidate plus BNZ (25 mg/kg/day/7 days) given on days 72 and 79 post-infection (p.i) (early chronic phase). Fibrosis, inflammation, and parasite burden were quantified in heart tissue at day 200 p.i. (late chronic phase). Further, spleen cells were collected to evaluate antigen-specific CD4+ and CD8+ T cell immune response, using flow cytometry. We found that vaccine-linked BNZ treated mice had lower cardiac fibrosis compared to the infected untreated control group. Moreover, cells from mice that received the immunotherapy had higher stimulation index of antigen-specific CD8+Perforin+ T cells as well as antigen-specific central memory T cells compared to the infected untreated control., Conclusions: Our results suggest that the bivalent immunotherapy together with BNZ treatment given during early chronic infection protects BALB/c mice against cardiac fibrosis progression and activates a strong CD8+ T cell response by in vitro restimulation, evidencing the induction of a long-lasting T. cruzi-immunity., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: María Elena Bottazzi and Peter J. Hotez are part of a team of scientists advancing research towards the development of a therapeutic Chagas disease vaccine and are listed among the inventors on Chagas disease vaccine patents submitted by Baylor College of Medicine and others. Author Fabian Gusovsky is employed by Eisai, Inc. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

There has been substantial research on adult COVID-19 and how to treat it. But how do severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections afflict children? The COVID-19 pandemic has yielded many surprises, not least that children generally develop less severe disease than older adults, which is unusual for a respiratory disease. However, some children can develop serious complications from COVID-19, such as multisystem inflammatory syndrome in children (MIS-C) and Long Covid, even after mild or asymptomatic COVID-19. Why this occurs in some and not others is an important question. Moreover, when children do contract COVID-19, understanding their role in transmission, especially in schools and at home, is crucial to ensuring effective mitigation measures. Therefore, in addition to nonpharmaceutical interventions, such as improved ventilation, there is a strong case to vaccinate children so as to reduce possible long-term effects from infection and to decrease transmission. But questions remain about whether vaccination might skew immune responses to variants in the long term. As the experts discuss below, more is being learned about these important issues, but much more research is needed to understand the long-term effects of COVID-19 in children.

The development of a new vaccine is a challenging exercise involving several steps including computational studies, experimental work, and animal studies followed by clinical studies. To accelerate the process, in silico screening is frequently used for antigen identification. Here, we present Vaxi-DL, web-based deep learning (DL) software that evaluates the potential of protein sequences to serve as vaccine target antigens. Four different DL pathogen models were trained to predict target antigens in bacteria, protozoa, fungi, and viruses that cause infectious diseases in humans. Datasets containing antigenic and non-antigenic sequences were derived from known vaccine candidates and the Protegen database. Biological and physicochemical properties were computed for the datasets using publicly available bioinformatics tools. For each of the four pathogen models, the datasets were divided into training, validation, and testing subsets and then scaled and normalised. The models were constructed using Fully Connected Layers (FCLs), hyper-tuned, and trained using the training subset. Accuracy, sensitivity, specificity, precision, recall, and AUC (Area under the Curve) were used as metrics to assess the performance of these models. The models were benchmarked using independent datasets of known target antigens against other prediction tools such as VaxiJen and Vaxign-ML. We also tested Vaxi-DL on 219 known potential vaccine candidates (PVC) from 37 different pathogens. Our tool predicted 175 PVCs correctly out of 219 sequences. We also tested Vaxi-DL on different datasets obtained from multiple resources. Our tool has demonstrated an average sensitivity of 93% and will thus be a useful tool for prioritising PVCs for preclinical studies., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

We conducted preclinical studies in mice using a yeast-produced SARS-CoV-2 RBD subunit vaccine candidate formulated with aluminum hydroxide (alum) and CpG deoxynucleotides. This formulation is equivalent to the CorbevaxTM vaccine that recently received emergency use authorization by the Drugs Controller General of India. We compared the immune response of mice vaccinated with RBD/alum to mice vaccinated with RBD/alum+CpG. We also evaluated mice immunized with RBD/alum+CpG and boosted with RBD/alum. Mice were immunized twice intramuscularly at a 21-day interval. Compared to two doses of the /alum formulation, the RBD/alum+CpG vaccine induced a stronger and more balanced Th1/Th2 cellular immune response, with high levels of neutralizing antibodies against the original Wuhan isolate of SARS-CoV-2 as well as the B.1.1.7 (Alpha), B.1.351 (Beta), B.1.617.2 and (Delta) variants. Neutralizing antibody titers against the B.1.1.529 (BA.1, Omicron) variant exceeded those in human convalescent plasma after Wuhan infection but were lower than against the other variants. Interestingly, the second dose did not benefit from the addition of CpG, possibly allowing dose-sparing of the adjuvant in the future. The data reported here reinforces that the RBD/alum+CpG vaccine formulation is suitable for inducing broadly neutralizing antibodies against SARS-CoV-2 including variants of concern.

The coronavirus disease 2019 (COVID-19) pandemic will change how we communicate biomedical science to reflect the new realities of increasing politicization of vaccines or therapeutics, as well as targeted attacks against prominent US scientists. The stakes are high, given how thousands of Americans are losing their lives by refusing vaccinations or demanding unproven treatments., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: MEB and PJH are developers of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E Ltd., a commercial vaccine manufacturer for scale up, production, testing and licensure. MG participates in one of eight SARS-CoV-2 vaccine development projects supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) since March 2020. MH is Founder and Managing Director of SaudiVax. JPF, GK and DCK are members of the WHO SAGE Working Group on COVID-19 vaccines. GK is independent director appointed by the Wellcome Trust, MSD Wellcome Trust Hilleman Laboratories Private Limited and Vice Chair of the Board, Coalition of Epidemic Preparedness Innovations (CEPI). DCK reports grants from Bill and Melinda Gates Foundation (BMGF) and grants from CEPI, JHK reports personal fees from SK biosciences. HL reports grants and honoraria from GlaxoSmithKline for training talks and from Merck as a member of the Merck Vaccine Confidence Advisory Board, grants from J&J outside the submitted work. AWS serves as Consultant to WHO. The views presented here reflect her views and not necessarily those of WHO. TS reports grants from National Institute of Allergy and Infectious Disease and Fast Grants and research contracts from GlaxoSmithKline, and ViiV Healthcare. SS reports grants from Ansun BioPharma, Astellas Pharma, Cidara Therapeutics, F2G, Merck, T2 Biosystems, Shire Pharmaceuticals, Shionogi, and Gilead Sciences, outside the submitted work; and personal fees from Amplyx Pharmaceuticals, Acidophil, Janssen Pharmaceuticals, Reviral, Intermountain Healthcare, Karyopharm Therapeutics, Immunome, Celltrion, and Adagio outside the submitted work. EH and S-JL are currently employed by FIND. All the other authors report no conflicts.

Competing Interests: FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose.

Competing Interests: The authors have no declarations to make.

In 2020, the state of Texas implemented coronavirus disease 2019 (COVID-19) social distancing guidelines in order to prevent surges at Texas hospital emergency rooms and in intensive care units. As noted in other states, an unintended consequence of these activities was significant declines in childhood immunizations. After analyzing state-wide immunization register data for Texas, we observed a 47% relative decline in immunization rates between 2019 and 2020 among 5-month-olds and a 58% decline among 16-month-olds. We observed a small decline (5%) among 24-month-olds, and no decline in vaccines received at birth (Hepatitis B). Declines were larger in rural counties compared to urban. These declines are superimposed on increases in state vaccine exemptions over the last five years due to an aggressive anti-vaccine movement in Texas. There are concerns that continued declines in childhood immunization coverage due to COVID-19 could lead to co-endemics of measles and other vaccine preventable diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Introduction: As a primary stability-indicating parameter, potency should be strategically evaluated during each phase of vaccine development. Herein, we present potency testing during the early clinical development of the Schistosoma mansoni ( Sm ) Tetraspanin-2 vaccine formulated on Alhydrogel (Sm -TSP-2/Al). As Sm -TSP-2/Al does not induce sterilizing immunity against its target pathogen ( Sm ) in animal models, potency is measured by " serological substitution", a method that can add significant variation to the potency metric, especially when used in a compliance (or ' single data point' ) approach., Methods: Potency data were analyzed using the compliance approach to determine if two clinical lots of Sm -TSP-2/Al retained potency over 84 and 36 months post-release, respectively. These same data were also analyzed by: i) least-squares regression with a joinpoint regression analysis; ii) control charting of stability slopes; and iii) bootstrap modeling. Nested-regression and bootstrapping were used to compare the potency of the first (#11-69F-003) and second (#1975) clinical lots of Sm -TSP-2/Al., Results: Despite significant variability in the immune assay, both clinical lots of Sm -TSP-2/Al remained potent for 84 and 36 months, respectively, in all four statistical approaches. The first lot of Sm -TSP-2/Al showed a gain in potency starting at 36 months post-release as captured by joinpoint regression. The two clinical lots of Sm -TSP-2/Al had comparable long-term potency., Conclusion: While a compliance approach can monitor the long-term stability of Sm -TSP-2/Al, it risks putting this critical stability-indicating parameter out of specification with each time point tested due to statistical multiplicity. Alternative statistical methods, such as joinpoint regression or bootstrapping, do not have this limitation and offer even more precise estimations of potency, with the added benefit of also providing predictive analytics. Nested regression and bootstrapping were shown to be a viable alternatives for lot-to-lot comparisons of the stability of Sm -TSP-2/Al. Instructions for implementing both these potency testing approaches are provided., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 The Authors.)

Competing Interests: MEB and PH are developers of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E Ltd., a commercial vaccine manufacturer for scale up, production, testing and licensure. MG participates in one of eight SARS-CoV-2 vaccine development projects supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) since March 2020. SG is cofounder of Vaccitech and has a patent on ChAdOx1 nCoV-19 licensed to AstraZeneca. MH is Founder and Managing Director of SaudiVax. JPF and GK are members of the WHO SAGE Working Group on COVID-19 vaccines. GK is independent director of Hilleman Laboratories Private Limited and Vice Chair of the Board, Coalition of Epidemic Preparedness Innovations (CEPI). DK reports grants from Bill and Melinda Gates Foundation (BMGF) and grants from CEPI. JK reports personal fees from SK biosciences. HL reports grants and honoraria from GlaxoSmithKline for training talks and from Merck as a member of the Merck Vaccine Confidence Advisory Board, outside the submitted work. TS reports grants from National Institute of Allergy and Infectious Disease and Fast Grants and research contracts from GlaxoSmithKline, and ViiV Healthcare. SS reports grants from Ansun BioPharma, Astellas Pharma, Cidara Therapeutics, F2G, Merck, T2 Biosystems, Shire Pharmaceuticals, Shionogi, and Gilead Sciences, outside the submitted work; and personal fees from Amplyx Pharmaceuticals, Acidophil, Janssen Pharmaceuticals, Reviral, Intermountain Healthcare, Karyopharm Therapeutics, Immunome, and Celltrion, outside the submitted work. All other authors declare no conflict of interests. The authors views and opinions in the Commentary do not necessarily represent the views, decisions, or policies of the institutions, universities, or health systems with which they are affiliated.

Competing Interests: MEB and PH are developers of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E Ltd., a commercial vaccine manufacturer for scale up, production, testing and licensure. MG participates in one of eight SARS-CoV-2 vaccine development projects supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) since March 2020. SG is cofounder of Vaccitech and has a patent on ChAdOx1 nCoV-19 licensed to AstraZeneca. MH is Founder and Managing Director of SaudiVax. JPF and GK are members of the WHO SAGE Working Group on COVID-19 vaccines. GK is independent director of Hilleman Laboratories Private Limited and Vice Chair of the Board, Coalition of Epidemic Preparedness Innovations (CEPI). DK reports grants from Bill and Melinda Gates Foundation (BMGF) and grants from CEPI. JHK reports personal fees from SK biosciences. HL reports grants and honoraria from GlaxoSmithKline for training talks and from Merck as a member of the Merck Vaccine Confidence Advisory Board, outside the submitted work. TS reports grants from National Institute of Allergy and Infectious Disease and Fast Grants and research contracts from GlaxoSmithKline, and ViiV Healthcare. SS reports grants from Ansun BioPharma, Astellas Pharma, Cidara Therapeutics, F2G, Merck, T2 Biosystems, Shire Pharmaceuticals, Shionogi, and Gilead Sciences, outside the submitted work; and personal fees from Amplyx Pharmaceuticals, Acidophil, Janssen Pharmaceuticals, Reviral, Intermountain Healthcare, Karyopharm Therapeutics, Immunome, and Celltrion, outside the submitted work. All other authors declare no conflict of interests. The authors views and opinions in the Commentary do not necessarily represent the views, decisions, or policies of the institutions, universities, or health systems with which they are affiliated.

Competing Interests: MEB and PH are developers of a COVID-19 vaccine construct, which was licensed by Baylor College of Medicine to Biological E Ltd., a commercial vaccine manufacturer for scale up, production, testing and licensure. MG participates in one of eight SARS-CoV-2 vaccine development projects supported by The Scientific and Technological Research Council of Turkey (TÜBİTAK) since March 2020. JK reports personal fees from SK biosciences. JPF and GK are members of the WHO SAGE Working Group on COVID vaccines. GK is independent director of Hilleman Laboratories Private Limited and Vice Chair of the Board, Coalition of Epidemic Preparedness Innovations (CEPI). SG has a patent ChAdOx1 licensed to Vaccitech, and a patent ChAdOx1 nCoV-19 licensed to AstraZeneca. SG also reports other work from Vaccitech outside the submitted work. MH is Founder and Managing Director of SaudiVax. HL reports grants and other from GSK, and grants and other from Merck, grants from J&J, outside the submitted work. TS reports grants from National Institute of Allergy and Infectious Disease, research contracts from GlaxoSmithKline, research contracts from ViiV Healthcare, and grants from Fastgrants. SS reports grants from Ansun, personal fees from Amplyx, grants from Astellas, personal fees from Acidophil, grants from Cidara, grants from F2G, personal fees from Jannssen, grants from Merck, grants from T2, personal fees from Reviral, grants from Shire, grants from Shionogi, grants from Gilead, personal fees from Intermountain Health, personal fees from Karyopharm, personal fees from Immunome, personal fees from Celltrion, outside the submitted work. NSW reports being a member of the steering committee of the COVID-19 research coalition and sponsor of a COVID-19 therapeutics trial. All other authors declare no conflict of interests. The authors views and opinions in the Commentary do not necessarily represent the views, decisions, or policies of the institutions, universities, or health systems with which they are affiliated.

The history of the neglected tropical disease movement is seen through the lens of authors who worked during the last 4 decades in different roles and in different settings, from Western-based laboratories to clinical roles in endemic countries and in critical policy roles in the World Health Organization (WHO). The authors seek to identify key players from the introduction of the word 'neglected' by the late Kenneth Warren in his Rockefeller Foundation-supported Great Neglected Diseases of Mankind movement through to the more recent developments after the London Declaration of 2012. The role of the various actors-endemic countries, major pharmaceutical companies, the WHO, non-government development organizations, bilateral donors and academia-are discussed. The critical events and decisions are highlighted that were essential enabling factors in creating a viable and successful movement and with a resultant massive global public health and antipoverty impact. The importance of advocacy is emphasized in creating the momentum to establish a globally recognized public health 'brand' as a target in the United Nations Sustainable Development Goals., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PJH has developed subunit vaccines against SARS and MERS coronavirus infection and is involved in the process of developing a vaccine against SARS-CoV-2.

Hookworm is an intestinal parasite that infects nearly 230 million people, with another 5.1 billion at risk, especially in poverty-stricken tropical and subtropical regions. Pregnancy is an especially vulnerable time for hookworm infection because of its effect on both maternal and subsequently fetal health. A systematic review and meta-analysis was conducted. The meta-analysis was performed on the association between maternal hookworm and maternal anemia, as well as maternal hookworm coinfection with malaria. The prevalence of hookworm ranged from 1% to 78% in pregnant women, whereas malaria prevalence ranged from 11% to 81%. Pregnant women with hookworm infection were more likely to have anemia (combined odds ratio [cOR] 2.55 [2.20, 2.96], P < 0.001). In addition, pregnant woman with hookworm were more likely to have malaria coinfection (cOR 1.60 [1.38, 1.86], P < 0.001). Other effects on maternal and child health were investigated and summarized without systematic review or meta-analysis because of the limited study numbers. Despite current deworming recommendations in pregnant women, heavy hookworm burden, coinfection with malaria, and subsequent anemia persist. Although this is likely due, in part, to a lack of implementation of preventive chemotherapy, additional interventions such as health education, proper waste management, or linking malaria and soil-transmitted helminth treatment and prevention programs may also be needed. Further investigations on maternal-child outcomes as a result of hookworm infection during pregnancy will highlight public health interventional targets to reduce morbidity in pregnant women and children globally.

[This corrects the article DOI: 10.1371/journal.pntd.0005574.].

Competing Interests: The authors declare no conflicts of interest exist.

Background: Toxoplasma gondii infection, if acquired as an acute infection during pregnancy, can have substantial adverse effects on mothers, fetuses and newborns. Latent toxoplasmosis also causes a variety of pathologies and has been linked to adverse effects on pregnancy., Objective: Here, we present results of a comprehensive systematic review and meta-analysis of the global prevalence of latent toxoplasmosis in pregnant women., Data Source: We searched PubMed, EMBASE, Web of Science, SciELO and Scopus databases for relevant studies that were published between 1 January 1988 and 20 July 2019., Study Eligibility Criteria: All population-based, cross-sectional and longitudinal studies reporting the prevalence of latent toxoplasmosis in healthy pregnant women were considered for inclusion., Participants: Pregnant women who were tested for prevalence of latent toxoplasmosis., Interventions: There were no interventions., Method: We used a random effects model to calculate pooled prevalence estimates with 95% confidence intervals (CIs). We grouped prevalence data according to the geographic regions defined by the World Health Organization (WHO). Multiple subgroup and meta-regression analyses were performed., Results: In total, 311 studies with 320 relevant data sets representing 1 148 677 pregnant women from 91 countries were eligible for inclusion in the meta-analysis. The global prevalence of latent toxoplasmosis in pregnant women was estimated at 33.8% (95% CI, 31.8-35.9%; 345 870/1 148 677). South America had the highest pooled prevalence (56.2%; 50.5-62.8%) of latent toxoplasmosis in pregnant women, whereas the Western Pacific region had the lowest prevalence (11.8%; 8.1-16.0%). A significantly higher prevalence of latent toxoplasmosis was associated with countries with low income and low human development indices (p < 0.001)., Conclusion: Our results indicate a high level of latent toxoplasmosis in pregnant women, especially in some low- and middle-income countries of Africa and South America, although the local prevalence varied markedly. These results suggest a need for improved prevention and control efforts to reduce the health risks to women and newborns., (Copyright © 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Purpose of Review: In this commentary, we summarize and put into perspective the recent information that highlights the associations between coronavirus disease and poverty. We also bring attention to another dimension that will most likely exacerbate the severity and long-term sequelae of COVID-19 in impoverished populations, that is, the comorbidities and the presence of tropical infections., Recent Findings: During this first half of 2020, the COVID-19 pandemic has emerged as a poverty-related neglected disease on at least two fronts. First, is its significant impact in low-income neighborhoods in the USA, the epicenter of the pandemic. Second, is its emergence in poor urban areas of South America, and now in Asia and Africa. In both fronts, the pandemic is contributing heavily towards the loss of public health gains that we managed to achieve globally during the last two decades. Specifically, any advances made as part of the United Nations Millennium Development Goals (United Nations, 2020) is eroding, and for the first time, the number of people entering extreme poverty is increasing. Adding to this descent into poverty are new disruptions in ongoing disease control programs, routine vaccination strategies, and a reduction of capacity building efforts globally. Therefore, and as highlighted by many others, we support the notion that a way forward to eliminate this coronavirus pandemic should include linking COVID-19 control to other tropical or poverty-related diseases., Summary: COVID-19 is slowing or reversing global health and development gains. To be successful and achieve the global goals including the control of pandemics such as the one seen from the COVID-19, we must rely on strong leadership leading to impactful public policies and global collaborations, including global COVID-19 vaccinations, and potentially linking them to programs for childhood and adult vaccinations and programs for malaria, tuberculosis, HIV/AIDS, and neglected tropical disease treatments. Opportunities also include the creation of unique research opportunities and funding models and increase science engagement for international diplomacy. This can only be done with a better understanding of the relationships between coronavirus disease, poverty, and tropical diseases., Competing Interests: Conflict of InterestMaria Elena Bottazzi and Peter Hotez are inventors of a low-cost COVID-19 vaccine for global health which was recently licensed by Baylor College of Medicine to a commercial third party for scale up and production., (© Springer Nature Switzerland AG 2020.)

Vaccination is one of public health's greatest achievements, responsible for saving billions of lives. Yet, 20% of children worldwide are not fully protected, leading to 1·5 million child deaths annually from vaccine-preventable diseases. Millions more people have severe disabling illnesses, cancers, and disabilities stemming from underimmunisation. Reasons for falling vaccination rates globally include low public trust in vaccines, constraints on affordability or access, and insufficient governmental vaccine investments. Consequently, an emerging crisis in vaccine hesitancy ranges from hyperlocal to national and worldwide. Outbreaks often originate in small, insular communities with low immunisation rates. Local outbreaks can spread rapidly, however, transcending borders. Following an assessment of underlying determinants of low vaccination rates, we offer an action based on scientific evidence, ethics, and human rights that spans multiple governments, organisations, disciplines, and sectors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background Chronic chagasic cardiomyopathy (CCC), caused by Trypanosoma cruzi infection, is an important public health problem attributable to progressive cardiomyopathy in patients, for which there is no cure. Chronic chagasic cardiomyopathy is characterized by myocarditis and cardiac fibrosis, which leads to life-threatening arrhythmogenic and circulatory abnormalities. This study aimed to investigate cardiac fibrosis progression in a mouse model of chronic chagasic cardiomyopathy. Methods and Results Cardiac cells infected with T cruzi produced significantly higher concentrations of transforming growth factor-β (TGF-β), connective tissue growth factor, endothelin-1, and platelet-derived growth factor-D than noninfected controls. Female Balb/c mice infected with T cruzi were compared with naïve mice. TGF-β genes and other TGF-β superfamily genes, as well as connective tissue growth factor, endothelin-1, and platelet-derived growth factor, were upregulated in infected mouse hearts. Serum concentrations of TGF-β, connective tissue growth factor, and platelet-derived growth factor-D were higher in infected mice and correlated with cardiac fibrosis. Strain analysis performed on magnetic resonance images at 111 and 140 days postinfection and echocardiography images at 212 days postinfection revealed significantly elevated left ventricular strain and cardiac fibrosis and concomitantly significantly decreased cardiac output in infected mice. Conclusions TGF-β, connective tissue growth factor and platelet-derived growth factor-D are potentially useful biomarkers of cardiac fibrosis, as they correlate with cardiac fibrosis. Strain analysis allows for use of noninvasive methods to measure fibrosis in the chronic stages of chagasic cardiomyopathy in a mouse model. These findings can be applied as noninvasive tools to study the effects of interventions and/or therapeutics on cardiac fibrosis development when using a mouse model of chronic chagasic cardiomyopathy.

Background: Schistosomiasis caused by Schistosoma mansoni (Sm) is a chronic, debilitating and potentially deadly neglected tropical disease. The licensure of a vaccine to prevent schistosomiasis would represent a major breakthrough in public health., Methods: The safety and immunogenicity of a candidate Sm vaccine were assessed in this phase I, double-blind, dose-escalation trial. Seventy-two healthy Sm-naïve 18-50 year olds were randomized to receive 3 doses ∼ 8 weeks apart of saline placebo, or 10 µg, 30 µg, or 100 µg of recombinant Sm-Tetraspanin-2 vaccine formulated on aluminum hydroxide adjuvant (Sm-TSP-2/Al) with or without 5 µg of glucopyranosyl lipid A aqueous formulation (GLA-AF). Clinical and serologic responses were assessed for 1 year after dose 3., Results: Vaccines were safe and well-tolerated. The most common reactions were injection site tenderness and pain, and headache and fatigue. Tenderness and pain were more frequent in groups receiving vaccine with GLA-AF than placebo (p = 0.0036 and p = 0.0014, respectively). Injection site reactions among those given Sm-TSP-2/Al with GLA-AF lasted 1.22 and 1.33 days longer than those receiving Sm-TSP-2/Al without GLA-AF or placebo (p < 0.001 for both). Dose- and adjuvant-related increases in serum IgG against Sm-TSP-2 were observed. Peak IgG levels occurred 14 days after dose 3. Seroresponse frequencies were low among recipients of Sm-TSP-2/Al without GLA-AF, but higher among subjects receiving 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF. More seroresponses were observed among those given 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF compared to placebo (p = 0.023 and p < 0.001, respectively). Seroresponse frequencies were 0%, 30%, 50%, and 89%, respectively, among those given placebo, or 10 µg, 30 µg or 100 µg of Sm-TSP-2/Al with GLA-AF, suggesting a dose-response relationship for Sm-TSP-2/Al with GLA-AF (p = 0.0001)., Conclusions: Sm-TSP-2/Al with or without GLA-AF was safe and well tolerated in a Sm-naïve population. A vaccine like the one under development may represent our best hope to eliminating this neglected tropical disease., (Copyright © 2019 Elsevier Ltd. All rights reserved.)