Nature20140306 OUTLOOK

OUTLOOK VACCINES Produced with support from: A global battle to prevent disease 6 M A R C H 2 0 1 4 | V O L 5 0 7 | N A T U R E | S 1 Editorial Herb Brody, Michelle Grayson, Tony Scully, Rachel Jones, Nick Haines Art & Design Wes Fernandes, Mohamed Ashour, Amr Rahma, Alisdair Macdonald, Andrea Duffy Production Karl Smart, Susan Gray, Ian Pope, Leonora Dawson-Bowling Sponsorship David Bagshaw, Yvette Smith, Reya Silao Marketing Elena Woodstock, Steven Hurst Project Manager Christian Manco Art Director Kelly Buckheit Krause Publisher Richard Hughes Magazine Editor Rosie Mestel Editor-in-Chief Philip Campbell Cover art: Nik Spencer Vaccines are a triumph of medicine. But the project to erect immunological shields against all deadly pathogens is far from complete, as is evident in this Outlook. Despite intense research into three of the world’s biggest killers — TB, malaria, and HIV — we still do not have an effective vaccine for any (page S4). Another disease that the western world has largely forgotten — polio — remains a scourge in a few poor countries. But the endgame is nigh; a strategy based on tweaking the vaccine’s composition over time is on target to eradicate this paralytic disease (S14). And a form of bacterial meningitis might soon be eradicated thanks to a powerful combination: government and industry (S16). For those diseases we can prevent, delivering vaccines to the people who need them most is far from simple. Most vaccines need to be kept within a narrow range of temperatures, lest they go bad. Progress is also being made on the ability to deliver vaccines through harsh environments without spoilage (S8). Vaccine development, historically a hit-and-miss process, could be on the cusp of a revolution in rational design, thanks to systems biology and its holistic view of living systems (S10). A major new player has entered the vaccine market. China, trying to shake off a reputation for scandal and inferior quality, has received World Health Organization approval to produce vaccines for Japanese encephalitis (S12). Meanwhile, a growing subset of the population is opting out of vaccinations. The predictable result: outbreaks of disease in areas corresponding to the vaccine refusal movement (S17). We are pleased to acknowledge the financial support of the New Venture Fund, United Nations Children’s Fund (UNICEF), and GAVI Alliance, as well as additional support from the Bill & Melinda Gates Foundation, in producing this Outlook. As always, Nature retains sole responsibility for all editorial content Herb Brody Supplements Editor S2 PUBLIC HEALTH The age of vaccines Routine vaccination has proven its worth, time for all children everywhere to benefit S4 INFECTIOUS DISEASE Beating the big three New ways to protect against malaria, HIV/AIDS and tuberculosis S8 LOGISTICS Keeping cool Delivering the goods when the heat is on S10 DRUG DEVELOPMENT Searching for patterns Systems biologists take on vaccines S12 PRODUCTION Vaccines from the East Can the Chinese maintain high-quality output? S14 POLIO The eradication endgame What will it take to finally end this threat? S16 PERSPECTIVE Elimination round We must act now to rid the world of epidemic infectious diseases, say Andrew Artenstein and Gregory Poland S17 PUBLIC HEALTH An injection of trust Addressing vaccine refusal head on S20 PERSPECTIVE Ill prepared for a pandemic Klaus Stöhr urges governments to ensure sufficient supplies of pandemic vaccines Nature Outlooks are sponsored supplements that aim to stimulate interest and debate around a subject of interest to the sponsor, while satisfying the editorial values of Nature and our readers’ expecta- tions. The boundaries of sponsor involvement are clearly delineated in the Nature Outlook Editorial guidelines available at http://www. nature.com/advertising/resources/pdf/outlook_guidelines.pdf CITING THE OUTLOOK Cite as a supplement to Nature, for example, Nature Vol XXX, No. XXXX Suppl, Sxx–Sxx (2014). VISIT THE OUTLOOK ONLINE The Nature Outlook Vaccines supplement can be found at http:// www.nature.com/nature/outlook/vaccines/ It features all newly commissioned content as well as a selection of relevant previously published material. All featured articles will be freely available for 6 months. SUBSCRIPTIONS AND CUSTOMER SERVICES For UK/Europe (excluding Japan): Nature Publishing Group, Subscriptions, Brunel Road, Basingstoke, Hants, RG21 6XS, UK. Tel: +44 (0) 1256 329242. Subscriptions and customer services for Americas – including Canada, Latin America and the Caribbean: Nature Publishing Group, 75 Varick St, 9th floor, New York, NY 10013-1917, USA. Tel: +1 866 363 7860 (US/Canada) or +1 212 726 9223 (outside US/Canada). Japan/China/Korea:Nature Publishing Group — Asia-Pacific, Chiyoda Building 5-6th Floor, 2-37 Ichigaya Tamachi, Shinjuku-ku, Tokyo, 162-0843, Japan. Tel: +81 3 3267 8751. CUSTOMER SERVICES Feedback@nature.com Copyright © 2014 Nature Publishing Group 6 March 2014 / VOL 507 / Issue No 7490 VACCINES OUTLOOK CONTENTS COLLECTION S22 Bettering BCG: a tough task for a TB vaccine? William Bishai & Zuri Sullivan, Barry R Bloom and Peter Andersen S24 Genomic correlates of variability in immune response to an oral cholera vaccine Partha P. Majumder et al. S31 Vaccines for the twenty-first century society Rino Rappuoli et al. S39 Molecular signatures of antibody responses derived from a systems biology study of five human vaccines Shuzhao Li et al. Nature Outlooks are sponsored supplements that aim to stimulate interest and debate around a subject of interest to the sponsor, while satisfying the editorial values of Nature and our readers’ expecta- tions. The boundaries of sponsor involvement are clearly delineated in the Nature Outlook Editorial guidelines available at http://www. nature.com/advertising/resources/pdf/outlook_guidelines.pdf CITING THE OUTLOOK Cite as a supplement to Nature, for example, Nature Vol XXX, No. XXXX Suppl, Sxx–Sxx (2014). To cite previously published articles from the collection, please use the original citation, which can be found at the start of each article. VISIT THE OUTLOOK ONLINE The Nature Outlook Vaccines supplement can be found at http:// www.nature.com/nature/outlook/vaccines/ All featured articles will be freely available for 6 months. SUBSCRIPTIONS AND CUSTOMER SERVICES For UK/Europe (excluding Japan):Nature Publishing Group, Subscriptions, Brunel Road, Basingstoke, Hants, RG21 6XS, UK. Tel: +44 (0) 1256 329242. Subscriptions and customer services for Americas – including Canada, Latin America and the Caribbean: Nature Publishing Group, 75 Varick St, 9th floor, New York, NY 10013-1917, USA. Tel: +1 866 363 7860 (US/Canada) or +1 212 726 9223 (outside US/Canada). Japan/China/Korea:Nature Publishing Group — Asia-Pacific, Chiyoda Building 5-6th Floor, 2-37 Ichigaya Tamachi, Shinjuku-ku, Tokyo, 162-0843, Japan. Tel: +81 3 3267 8751. CUSTOMER SERVICES Feedback@nature.com Copyright © 2014 Nature Publishing Group © 2014 Macmillan Publishers Limited. All rights reserved S 2 | N A T U R E | V O L 5 0 7 | 6 M A R C H 2 0 1 4 THE AGE OF VACCINES �e advent of routine childhood vaccination has led to dramatic declines in many contagious diseases in the United States. Maintaining these gains there and spreading these success worldwide is challenge for public health. By Tony Scully. OUT OF COVERAGE If a child receives the three doses of the DTP vaccines they are likely to have completed routine childhood vaccination – a useful proxy for routine vaccination coverage. Among the 22.6 million children who did not receive the three doses, nearly 8.4 million started but failed to complete — pointing to poor health infrastructure. For the 14 million that never received the �rst dose, it seems that parental refusal is a major factor. OUT OF COVERAGE If a child receives the three doses of the DTP vaccines they are likely to have completed routine childhood vaccination – a useful proxy for routine vaccination coverage. Among the 22.6 million children who did not receive the three doses, nearly 8.4 million started but failed to complete — pointing to poor health infrastructure. For the 14 million that never received the �rst dose, it seems that parental refusal is a major factor. 7.4M4.2M 1.8M 1.2M 0.9M 0.8M 0.3M 0.3M 0.3M 0.3M S O U R C E: W H ODropped out after �rst dose Received no dose Dropped out after �rst dose Received no dose Over half of all undervaccinated children lived in only three countries – India, Nigeria and Indonesia, while 72% lived in ten countries. 0 20 40 60 80 100 C ov er ag e (% ) Africa The Americas Eastern Mediterranean Europe South East Asia Western Pacific THE R IGHT D IRECTION Since the early 1980s, vaccine coverage has risen rapidly. During 2012, 131 countries achieved ≥90% national DTP3 coverage, and 30% achieved ≥80% DTP3 coverage in every district. Developing programmes to suit each country will help ensure that enough children are being protected against vaccine-preventable diseases (see 'Keeping cool', page S8). THE R IGHT D IRECTION Since the early 1980s, vaccine coverage has risen rapidly. During 2012, 131 countries achieved ≥90% national DTP3 coverage, and 30% achieved ≥80% DTP3 coverage in every district. Developing programmes to suit each country will help ensure that enough children are being protected against vaccine-preventable diseases (see 'Keeping cool', page S8). 90% 80% S O U R C E: W H O The Global Vaccine Action Plan (GVAP) is a plan to increase vaccine coverage to 80% for countries and 90% at a regional level. The Global Vaccine Action Plan (GVAP) is a plan to increase vaccine coverage to 80% for countries and 90% at a regional level. 90%80% Coverage ranges from 72% in Africa to to 97% in the Western Paci�c Region. THE USUAL SUSPECTS Several highly infectious diseases have been brought under control by routine childhood vaccination, although complacency can lead to resurgence in disease. Diptheria This bacterial infection can damage heart muscle and the nervous system, leading to paralysis and respiratory failure. Diptheria This bacterial infection can damage heart muscle and the nervous system, leading to paralysis and respiratory failure. Pertussis Better known as whooping cough, infection can last up to 6 weeks. Each year, 50 million cases worldwide and 300,000 deaths. Pertussis Better known as whooping cough, infection can last up to 6 weeks. Each year, 50 million cases worldwide and 300,000 deaths. Polio Crippling viral infection all but eliminated world but for a few countries (see page S14). Polio Crippling viral infection all but eliminated world but for a few countries (see page S14). Measles Respiratory infection that can cause body rash. Estimated 1 in every 5,000 people with measles will die from complications. Measles Respiratory infection that can cause body rash. Estimated 1 in every 5,000 people with measles will die from complications. Mumps Highly infectious virus causing glands to swell, giving a chipmunk-like appearance. Complications can lead to deafness or aseptic meningitis. Mumps Highly infectious virus causing glands to swell, giving a chipmunk-like appearance. Complications can lead to deafness or aseptic meningitis. Rubella If a pregnant women catches the usually mild infection, unborn child has a two in three chance of developing syndrome, including deafness and metal disability. Rubella If a pregnant women catches the usually mild infection, unborn child has a two in three chance of developing syndrome, including deafness and metal disability. Hepatitis A Flu-like viral infection usually contracted by consuming tainted food or water. Illness more severe if liver becomes infected. Hepatitis A Flu-like viral infection usually contracted by consuming tainted food or water. Illness more severe if liver becomes infected. A H ISTORY OF D ISEASE REDUCTION An analysis of weekly disease surveillance recorded at the state level by the US Centre for Disease Control and Prevention reveals how many major threats to public health have been a�ected by the introduction of a vaccine; an estimated 103 million cases of childhood diseases since 1924. A H ISTORY OF D ISEASE REDUCTION An analysis of weekly disease surveillance recorded at the state level by the US Centre for Disease Control and Prevention reveals how many major threats to public health have been a�ected by the introduction of a vaccine; an estimated 103 million cases of childhood diseases since 1924. KEY 1948Diptheria, Tetanus and Pertussis (DTP) vaccine 1955 Polio vaccine 1963 Measles vaccine 1967 Mumps vaccine 1995 Hepatitis A vaccine 1969 Rubella vaccine MumpsDiptheria Measles Hepatitis A Rubella Polio Pertussis N u m b er o f ca se s SOURCE: VAN PANHUIS, W. G. ET AL. N. ENGL. J. MED. 369, 2152–2158 (2013) ––– YEAR 1920 19401930 1950 1955 1960194519351925 1975 1985 1995 200519701965 1980 1990 2000 2010 10 100 1,000 10,000 100,000 1,000,000 N u m b er o f ca se s 10 100 1,000 10,000 100,000 1,000,000 Diptheria, Tetanus and Pertussis There were once 100,000 to 200,000 cases of diphtheria reported each year; now exceedingly rare. In the mid-1940s, the diphtheria toxoid vaccine was combined with vaccines against tetanus and pertussis. Polio In 1952, 53,000 people died and a futher 20,000 were paralyzed. Complacency breeds germs Since the early 1980s, the anti-vaccination movement has led to a drop in coverage and the resurgence of disease (See 'An injection of trust', page S17). US declared polio free in 1979 (see 'Eradication endgame', page S14). Measles Incidence fell dramatically following introd- uction of the vaccine. Outbreaks in the 1970s led to increased vaccine uptake and cases have fallen to only a few hundred per year. Pertussis About 38,000 cases of pertussis reported in 2012, the most since 1959. 103 million cases of childhood diseases have been prevented in the United States since 1924. 103M 55% of DTP unvaccinated infants lived in only 3 countries. VACCINESOUTLOOK © 2014 Macmillan Publishers Limited. All rights reserved 6 M A R C H 2 0 1 4 | V O L 5 0 7 | N A T U R E | S 3 THE AGE OF VACCINES �e advent of routine childhood vaccination has led to dramatic declines in many contagious diseases in the United States. Maintaining these gains there and spreading these success worldwide is challenge for public health. By Tony Scully. OUT OF COVERAGE If a child receives the three doses of the DTP vaccines they are likely to have completed routine childhood vaccination – a useful proxy for routine vaccination coverage. Among the 22.6 million children who did not receive the three doses, nearly 8.4 million started but failed to complete — pointing to poor health infrastructure. For the 14 million that never received the �rst dose, it seems that parental refusal is a major factor. OUT OF COVERAGE If a child receives the three doses of the DTP vaccines they are likely to have completed routine childhood vaccination – a useful proxy for routine vaccination coverage. Among the 22.6 million children who did not receive the three doses, nearly 8.4 million started but failed to complete — pointing to poor health infrastructure. For the 14 million that never received the �rst dose, it seems that parental refusal is a major factor. 7.4M4.2M 1.8M 1.2M 0.9M 0.8M 0.3M 0.3M 0.3M 0.3M S O U R C E: W H ODropped out after �rst dose Received no dose Dropped out after �rst dose Received no dose Over half of all undervaccinated children lived in only three countries – India, Nigeria and Indonesia, while 72% lived in ten countries. 0 20 40 60 80 100 C ov er ag e (% ) Africa The Americas Eastern Mediterranean Europe South East Asia Western Pacific THE R IGHT D IRECTION Since the early 1980s, vaccine coverage has risen rapidly. During 2012, 131 countries achieved ≥90% national DTP3 coverage, and 30% achieved ≥80% DTP3 coverage in every district. Developing programmes to suit each country will help ensure that enough children are being protected against vaccine-preventable diseases (see 'Keeping cool', page S8). THE R IGHT D IRECTION Since the early 1980s, vaccine coverage has risen rapidly. During 2012, 131 countries achieved ≥90% national DTP3 coverage, and 30% achieved ≥80% DTP3 coverage in every district. Developing programmes to suit each country will help ensure that enough children are being protected against vaccine-preventable diseases (see 'Keeping cool', page S8). 90% 80% S O U R C E: W H O The Global Vaccine Action Plan (GVAP) is a plan to increase vaccine coverage to 80% for countries and 90% at a regional level. The Global Vaccine Action Plan (GVAP) is a plan to increase vaccine coverage to 80% for countries and 90% at a regional level. 90%80% Coverage ranges from 72% in Africa to to 97% in the Western Paci�c Region. THE USUAL SUSPECTS Several highly infectious diseases have been brought under control by routine childhood vaccination, although complacency can lead to resurgence in disease. Diptheria This bacterial infection can damage heart muscle and the nervous system, leading to paralysis and respiratory failure. Diptheria This bacterial infection can damage heart muscle and the nervous system, leading to paralysis and respiratory failure. Pertussis Better known as whooping cough, infection can last up to 6 weeks. Each year, 50 million cases worldwide and 300,000 deaths. Pertussis Better known as whooping cough, infection can last up to 6 weeks. Each year, 50 million cases worldwide and 300,000 deaths. Polio Crippling viral infection all but eliminated world but for a few countries (see page S14). Polio Crippling viral infection all but eliminated world but for a few countries (see page S14). Measles Respiratory infection that can cause body rash. Estimated 1 in every 5,000 people with measles will die from complications. Measles Respiratory infection that can cause body rash. Estimated 1 in every 5,000 people with measles will die from complications. Mumps Highly infectious virus causing glands to swell, giving a chipmunk-like appearance. Complications can lead to deafness or aseptic meningitis. Mumps Highly infectious virus causing glands to swell, giving a chipmunk-like appearance. Complications can lead to deafness or aseptic meningitis. Rubella If a pregnant women catches the usually mild infection, unborn child has a two in three chance of developing syndrome, including deafness and metal disability. Rubella If a pregnant women catches the usually mild infection, unborn child has a two in three chance of developing syndrome, including deafness and metal disability. Hepatitis A Flu-like viral infection usually contracted by consuming tainted food or water. Illness more severe if liver becomes infected. Hepatitis A Flu-like viral infection usually contracted by consuming tainted food or water. Illness more severe if liver becomes infected. A H ISTORY OF D ISEASE REDUCTION An analysis of weekly disease surveillance recorded at the state level by the US Centre for Disease Control and Prevention reveals how many major threats to public health have been a�ected by the introduction of a vaccine; an estimated 103 million cases of childhood diseases since 1924. A H ISTORY OF D ISEASE REDUCTION An analysis of weekly disease survei