PERSPECTIVES expectancy is above 80 years and, bearing SCIENCE AND SOCIETY in mind that predictions of a ceiling to life expectancy have been repeatedly wrong, Vaccines for the twenty-first century we can extrapolate that it could reach 100 years in six decades2. A major reason society for the steady increase of life expectancy is greater control of infectious diseases — this has led to decreased early mortality Rino Rappuoli, Christian W. Mandl, Steven Black and Ennio De Gregorio (only one in four children used to reach the Abstract | Vaccines have been one of the major revolutions in the history of age of 20) and has also provided a longer lifespan in adults by decreasing their expo- mankind and, during the twentieth century, they eliminated most of the childhood sure to acute and chronic inflammatory diseases that used to cause millions of deaths. In the twenty-first century, vaccines processes1. will also play a major part in safeguarding people’s health. Supported by the Vaccination served extremely well the innovations derived from new technologies, vaccines will address the new needs needs of our twentieth-century society, of a twenty-first century society characterized by increased life expectancy, members of which had a life expectancy of approximately 55–65 years. By eliminating emerging infections and poverty in low-income countries. many infectious diseases that used to cause millions of deaths, vaccination contributed Health is probably the most important value average lifespan was 35 years in 1750 to the increase in our lifespan (FIG. 1). of our society, which enjoys an unprecedented (REF. 1) and 45 years in 1840, and this has Key contributions made by vaccination quality of life in high-income countries and since increased by approximately 2.5 years include the eradication of smallpox from improving conditions in poor countries. A per decade, reaching 55 years in 1900 our planet, the almost complete elimina- lot of the progress made so far in improving and 65 years in 1950 (REFS 2,3). Today, life tion of poliomyelitis, and a decrease of healthcare has been due to the conquest of infectious diseases, an area in which vaccina- Box 1 | Recently launched vaccine initiatives tion has played a major part. During the past Decade of Vaccines three decades, the vaccine field has been trans- An initiative launched by the Bill and Melinda Gates Foundation at the World Economic Forum in formed by new technologies, and vaccination Davos, Switzerland in January 2010 (REF. 30), committing US$10 billion to research, develop and has the potential to have a very important role deliver vaccines for the poorest countries, with the aim to save 8–10 million lives by 2020. The in the future as well. There is much excitement initiative is working on a global vaccine action plan to increase the collaboration among the about the contributions that vaccines have international community. The plan is being developed by four working groups addressing global made and will continue to make to our society access, research and development, delivery and public and political support. In addressing the this century, and several initiatives have been World Health Assembly, Bill Gates stated that “vaccines are one of the best investments we can launched to better capture the full potential of make” in the future because “healthy people can drive thriving economies” (REF. 26). The plan what vaccines may deliver. The most impor- includes eradicating polio early in this decade and making five or six new vaccines available to tant ones are the Decade of Vaccines launched all children of the world by the end of the decade. by the Bill and Melinda Gates Foundation, the Millennium Development Goals Millennium Development Goals of the United An initiative launched in 2000 by the world leaders at United Nations Headquarters in New York Nations, and the initiative of the US Institute that identified eight Millennium Development Goals to halve extreme poverty, halt the spread of HIV/AIDS and provide universal primary education by the target date of 2015 (REF. 31). Several of Medicine to identify and prioritize new of the goals include vaccination as one of the important means by which to achieve the goal. (BOX 1) preventive vaccines for development . Typical among these are goals one and four, which aim to reduce poverty and child mortality, Here, we describe how vaccines may con- respectively, and goal five, which aims to improve maternal health. tribute to addressing the health needs of the US Institute of Medicine consensus study: Identifying and Prioritizing New Preventive twenty-first century, which is characterized Vaccines for Development by an aging society, emerging infections and An initiative set up by the US Institute of Medicine in September 2010, with the aim to develop poverty in low-income countries. an evidence-based approach and methodology to identify and prioritize the needs for new preventive vaccines of domestic and global importance32. An ad hoc committee of the Institute Vaccines for all ages of Medicine has been assembled to review the research and development prioritization One of the great successes of modern activities in the USA and worldwide. The aim is to identify new preventive vaccine targets and society in high-income countries is the develop an analytical framework and model for prioritizing vaccine interventions of domestic increase in life expectancy (FIG. 1). In and global importance. The committee is expected to prepare a report containing the analytical countries with the longest life expectancy, framework and model for evaluating and prioritizing vaccine targets by March 2012. NATURE REVIEWS | IMMUNOLOGY VOLUME 11 | DECEMBER 2011 | 865 © 2012 Macmillan Publishers Limited. All rights reserved PERSPECTIVES group in the twenty-first century could be hepatitis B virus, H. influenzae type b, addressed by vaccination (FIG. 2). poliovirus, Streptococcus pneumoniae, 6QFC[oUUQEKGV[ 5,6 rotavirus, measles, mumps and rubella Pre-birth. In the past, pregnant women had (FIG. 2a). This immunization schedule high levels of antibodies against a range of should remain in place, and further pathogens to which they had been exposed, immunizations against meningococcus, and they transferred protective immunity respiratory syncytial virus, influenza virus, to their unborn fetus and then to their group A streptococcus and Helicobacter newborn baby via transplacental transfer pylori can be added to the schedule of antibodies and by breast feeding. Today, when these vaccines become available. young women are less exposed to infectious Vaccination against hepatitis A virus can 5QEKGV[HQTYJKEJOQUV XCEEKPGUYGTGFGXGNQRGF agents, and breast feeding is less common also be added to the schedule. .KHGGZRGEVCPE[ [GCTU and of shorter duration. Therefore, mothers Importantly, once a proper programme transfer fewer protective antibodies to their of maternal immunization is implemented, infants. The consequence is that newborns it will be possible to relax the aggres- are not protected against various pathogens sive immunization schedules of today, in and diseases, including cytomegalovirus, which children receive immunizations at influenza virus, group B streptococcus, 2, 3, 4 and 12 months of age or at 2, 4, 6 hepatitis B virus, meningococcus (groups and 12 months of age5,6. Although these Figure 1 | Increase in life;GCT expectancy. The A, B, C, Y and W135), pertussis, respiratory schedules are designed to induce protec- graph shows the increase in life expectancy that syncytial virus and tetanus. With the excep- tive immunity early in life, they are not occurred in the countries0CVWTG4GXKGYU with ^longest+OOWPQNQI[ lifes- tion of the hepatitis B virus vaccine and optimal for effective priming of the still- 1–3 pans from 1750 to the present day and also the bacille Calmette–Guérin (BCG) that in some immature immune system. Better priming, projected increase in longevity for this century. countries are given at birth, present immuni- and different regimes, such as immuniza- The average life expectancy for individuals in the zation schedules start mostly at two months tion at 3 and 5 months with a booster at society for which most vaccines were developed 5,6 was 60–65 years. This society was characterized of age . Consequently, the present immu- 12 months may be considered. We need, by a high proportion of children and young peo- nization schedules do not induce protection however, to ensure that maternal immu- ple, and is quite different from today’s society, against the majority of these diseases until nization does not interfere with infant which is characterized by a high proportion of the fifth month of life or later. This leaves vaccination, since it is well known that elderly people and a life expectancy of more a period of vulnerability during the first the presence of maternal antibodies can than 80 years. 4–6 months of life, which is associated with prevent the infants from mounting optimal significant mortality and morbidity. A recent immune responses against live-attenuated increase in the frequency of pertussis cases viral vaccines, such as that used for mea- more than 95% in the incidence of diseases and subsequent mortality in infants younger sles, by interfering with viral replication. such as diphtheria, tetanus, pertussis, than 5 months is an example of this trend7. These effects are usually not present, even measles, mumps and rubella. More Recent successes involving the vaccina- if in some cases they have been reported recently, vaccines against hepatitis A, hepa- tion of pregnant women against neonatal for inactivated vaccines, such as whole- titis B, Haemophilus influenzae type b and tetanus8 and influenza virus9 in order to cell pertussis, and therefore their presence pneumococcus have further decreased the promote immunity in neonates have shown needs to be assessed for each new vaccine10. mortality caused by infectious diseases4. that vaccination before birth is safe and The key question for this article is very effective in providing newborns and Adolescents.