Vaccines, Autism, and “Blue Marble” Health
Peter Hotez, M.D., Ph.D.
Texas Children’s Hospital Endowed @PeterHotez Chair in Tropical Pediatrics
Dean, National School of Tropical Medicine at Baylor College of Medicine
Former US Science Envoy The Global Goals (and a new world order)
Current New World Order Anti‐science Regional Conflicts Climate Change US/UK Retreat from Globalization, China’s neo‐Silk Road,
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xxx00.#####.ppt 5/31/2018 12:12:47 PM Page 3 xxx00.#####.ppt 5/31/2018 12:12:48 PM The Global Burden of Disease 1990-2013
Expanded use of vaccines • 83% reduction in measles deaths • 82% reduction in tetanus deaths • 57% reduction in diphtheria/pertussis deaths • 45% reduction in Hib deaths
Development new vaccines • Pneumococcal disease (36% reduction in deaths) • Rotavirus (63% reduction in deaths)
2.5 million childhood lives saved through these initiatives
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xxx00.#####.ppt 5/31/2018 12:12:48 PM Measles • Decline of Measles ‐1980 – 2 million deaths ‐1990 – 900,000 deaths ‐2000 – 600,000 deaths ‐2016 – 68,000 deaths
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xxx00.#####.ppt 5/31/2018 12:12:48 PM Measles Transmissibility
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xxx00.#####.ppt 5/31/2018 12:12:48 PM Page 7 xxx00.#####.ppt 5/31/2018 12:12:48 PM 20 Years of ‘Vaccine Hesitancy’ 1998-2018
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xxx00.#####.ppt 5/31/2018 12:12:48 PM Page 9 xxx00.#####.ppt 5/31/2018 12:12:48 PM Page 10 xxx00.#####.ppt 5/31/2018 12:12:49 PM 2014-15 California Measles Outbreak
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xxx00.#####.ppt 5/31/2018 12:12:49 PM 2011‐12 2016‐17
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xxx00.#####.ppt 5/31/2018 12:12:49 PM • Texas ranks at the bottom of fully immunized children • >50,000 Public School Personal Belief Exemptions in Texas
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xxx00.#####.ppt 5/31/2018 12:12:49 PM Page 14 xxx00.#####.ppt 5/31/2018 12:12:49 PM Page 15 xxx00.#####.ppt 5/31/2018 12:12:49 PM 2013 & 2018 Texas Measles Outbreaks
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xxx00.#####.ppt 5/31/2018 12:12:50 PM Measles outbreak Twin Cities MN
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xxx00.#####.ppt 5/31/2018 12:12:50 PM Vaccine as the next “Tuskegee”
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xxx00.#####.ppt 5/31/2018 12:12:50 PM Melanie’s Marvelous Measles
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xxx00.#####.ppt 5/31/2018 12:12:50 PM Page 20 xxx00.#####.ppt 5/31/2018 12:12:50 PM Antivax Rise in US States Non‐Medical Exemptions
7.50 7.00 6.50 6.00 5.50 5.00 4.50 4.00 3.50 3.00 2.50 2.00 1.50 1.00 0.50 0.00 Percent kindergarteners with NMEs of
School Year
2009-2010 2010-2011 2011-2012 2012-2013 2013-2014 2014-2015 2015-2016
Jackie Olive Page 21
xxx00.#####.ppt 5/31/2018 12:12:51 PM US Anti-Vax “Hotspots”
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xxx00.#####.ppt 5/31/2018 12:12:51 PM Pediatrician, Vaccine Scientist , Autism Dad
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xxx00.#####.ppt 5/31/2018 12:12:51 PM How the Anti‐Vaxxers are Winning
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xxx00.#####.ppt 5/31/2018 12:12:52 PM Page 25 xxx00.#####.ppt 5/31/2018 12:12:52 PM Page 26 xxx00.#####.ppt 5/31/2018 12:12:52 PM The Neurobiology of Autism
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xxx00.#####.ppt 5/31/2018 12:12:52 PM Page 28 xxx00.#####.ppt 5/31/2018 12:12:52 PM Science and Public Engagement
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xxx00.#####.ppt 5/31/2018 12:12:52 PM September 2018
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xxx00.#####.ppt 5/31/2018 12:12:53 PM David Letterman Quote and CEPI
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xxx00.#####.ppt 5/31/2018 12:12:53 PM The Neglected Tropical Diseases
• 20 tropical infections: ‐Highly prevalent among the poor ‐Endemic in rural areas of low-income countries ‐Ancient afflictions ‐Chronic ‐Disabling (growth delays, blindness or disfigurement) ‐Stigmatizing ‐Poverty promoting
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xxx00.#####.ppt 5/31/2018 12:12:53 PM NTDs: GBD 2016
Ascariasis 799.7 million Trachoma 3.4 million Hookworm disease 450.7 million Cysticercosis* 2.7 million Trichuriasis 435.1 million Echinococcosis* 974,000 Schistosomiasis* 189.8 million Hansen’s Disease* 523,000 Scabies* 146.7 million Rabies* 13,000 Dengue* 101.1 million African Trypanosomiasis* 5,000 Food-borne* 74.7 million Ebola* 1.000 trematodiases Guinea worm* <1,000 Lymphatic Filariasis* 29.4 million Yaws Not determined Onchocerciasis* 14.6 million Buruli ulcer Not determined Chagas disease* 7.2 million Mycetoma Not determined Leishmaniasis* 4.8 million Zika* 7.6 million *Incidence instead of prevalence
Page 33 33 *Zoonotic or vector‐borne disease xxx00.#####.ppt 5/31/2018 12:12:54 PM NTD Scale up with the U.S. Government + Drug Donations from
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xxx00.#####.ppt 5/31/2018 12:12:54 PM Texas Children’s Hospital Center for Vaccine Development
• Expanded • Built Hookworm • Added 7 2000 structure 2004 Program 2011 additional to • Launched to • Schisto to programs 2004 Hookworm 2011 Program 2015 • Expansion of Program • Relocated to capabilities TMC
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xxx00.#####.ppt 5/31/2018 12:12:54 PM Rino Rappuoli: Reverse Vaccinology
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xxx00.#####.ppt 5/31/2018 12:12:55 PM Reverse vaccinology as a ‘holy grail’ for complex eukaryotic organisms
‐Large genomes of similar complexity to human genome ‐Inadequacy of bacterial expression systems for eukaryotic antigens ‐Low throughput not high throughput ‐Deficiencies in animal models
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xxx00.#####.ppt 5/31/2018 12:12:55 PM Vaccine Targeting Hookworm and Schistosomiasis Co-Infections
A MULTIVALENT VACCINE TARGETING HOOKWORM + SCHISTO
P C C W/F/Y EC‐2
C G C C G C EC‐1 E/Q
G/A G/A E/Q 1 2 3 4 G/A F/Y E/Q membrane G/A K
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xxx00.#####.ppt 5/31/2018 12:12:55 PM Goals of Anti-schistosome Vaccine
• Worm burden reduction • Egg reduction • Reduced end-organ pathology • Reduction in inflammation • Reduction in anemia and malnutrition
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xxx00.#####.ppt 5/31/2018 12:12:55 PM Immunomics Approach: Schistosome protein microarrays
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xxx00.#####.ppt 5/31/2018 12:12:55 PM Immune localization of Sm-TSP-2
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xxx00.#####.ppt 5/31/2018 12:12:55 PM Suppression of tsp-2 mRNA expression results in impaired tegument turnover in vitro
Tran et al. PLoS Path 2010
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xxx00.#####.ppt 5/31/2018 12:12:56 PM Targeting Blood-feeding in the Hookworm Gut in Phase 1 Trials
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Hotez, Bethony, Diemert, Pearson, Loukasxxx00.#####.ppt (2010) Nature 5/31/2018 Rev 12:12:56 Microbiol PM Na‐APR‐1 protects against Necator and Nippostrongylus
Priming with 100L3 Nippo or Necator IV, D‐30 or Vaccination protein+Alum SC, D‐30, D‐23, D‐16 Challenge SC with 550 L3 of Nippostrongylus
250 D6 ‐ gut
200
Anti-APR-1 150 Antibodies 100 in *** *** *** Hookworm 50 Gut b 0 b N b N + b N + m N 2 ri + 1 P p + r R S B to A b a P - N N c -A A e a N n N
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xxx00.#####.ppt 5/31/2018 12:12:56 PM Human Hookworm Vaccine US vs. Brazil Cohorts
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xxx00.#####.ppt 5/31/2018 12:12:56 PM Economic Return of an Anti- Hookworm Anemia Vaccine
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xxx00.#####.ppt 5/31/2018 12:12:57 PM Three Major Drivers of 21st Century NTDs
Poverty •Health •Poverty system •Blue • Conflict collapse Marble Health Conflict Climate
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xxx00.#####.ppt 5/31/2018 12:12:57 PM CONFLICT & POLITICAL DESTABILIZATION: ISIS-occupied Syria, Iraq, Libya, Yemen
• Measles/Polio • Leishmaniasis • Schistosomiasis • Brucellosis • MERS CoV • Dengue and RVF • Malaria/TB • Cholera
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xxx00.#####.ppt 5/31/2018 12:12:58 PM “Aleppo Evil”: Cutaneous Leishmaniasis in Syria, Iraq, Afghanistan and Yemen
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xxx00.#####.ppt 5/31/2018 12:12:58 PM Leishmaniasis Vaccine: PpSp15 (sandfly) + LdNH36 (parasite)
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xxx00.#####.ppt 5/31/2018 12:12:58 PM U.S. Science Envoy Program
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xxx00.#####.ppt 5/31/2018 12:12:58 PM POVERTY: “Blue Marble Health”
‐Neglected diseases of the poor living amidst wealth ‐A new framework for global science policy and the poverty-related diseases
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xxx00.#####.ppt 5/31/2018 12:12:58 PM BLUE MARBLE HEALTH: The Poor Living Among the Wealthy (G20 + Nigeria)
WHO + GBD 2013 • 73-78% Leprosy • 61-78% Chagas • 60-61% Dengue • 57-60% TB • 45-67% VL • 50-52% Helminths
• STH • Schistosomiasis G20 + Nigeria = 54% Population • Lymphatic and 86% Global Economy Filariasis • Onchocerciasis
Hotez PJ (2013) NTDs V.2.0: “Blue Marble Health”—Neglected Tropical Disease Control and Elimination in a Shifting Health Policy Landscape. PLoS Negl Trop Dis Page 53 7(11): e2570. doi:10.1371/journal.pntd.0002570 http://www.plosntd.org/article/info:doi/10.1371/journal.pntd.00xxx00.#####.ppt02570 5/31/2018 12:12:58 PM Hookworm disease in Alabama
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xxx00.#####.ppt 5/31/2018 12:12:59 PM Chagas disease transmission in Texas
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xxx00.#####.ppt 5/31/2018 12:12:59 PM Tc24 protein combined with E6020 in a Stable Squalene Emulsion as a lead candidate vaccine
Candidate Antigen Candidate Adjuvant
Tc24‐ 24kDa Trypanosoma Cruzi TLR4 agonist: Flagellar Calcium Binding Protein P P
+ E6020
Additional antigens also under evaluation and development
Page 56 56 xxx00.#####.ppt 5/31/2018 12:12:59 PM Therapeutic Chagas Disease Vaccine
Increased Ag‐specific IFNγ Decreased T. cruzi burden Decreased Cardiac fibrosis
Experimental Chagas disease vaccine improves Cardiac Echocardiography function
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xxx00.#####.ppt 5/31/2018 12:12:59 PM Elie Wiesel: 1928-2016
• Man’s weakness is not in achieving victories but in taking advantage of them
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