Vaccines and Antivirals: Grand Challenges and Great Opportunities

Abstract

In the last decades, emerging and reemerging infectious diseases marked the third epidemiological transition (Figure 1A), characterized by: (i) identification of new emerging diseases; (ii) increased incidence and prevalence of preexisting infectious diseases; (iii) appearance of antimicrobial-resistant strains (1). These trends occur within a context of globalization, international trade, migration, and ecological changes. Figure 1. The perpetual challenge of viral infections. (A) Epidemiological transitions. Communicable diseases became known when human beings organized in prehistoric hunter-gatherer societies. About 10,000 years ago, the Neolithic Revolution, also called the first agricultural revolution occurred, which was characterized by a transition from a nomadic hunting and gathering lifestyle to sedentariness (1). The introduction of agriculture and of domestication and herding of animals created the conditions for a rise in infectious diseases, known as the first epidemiological transition. Infectious diseases such as malaria, tuberculosis, leprosy, influenza, and smallpox were already present several millennia ago. In the mid-nineteenth century, the second epidemiologic transition took place with the industrial revolution, featured by a shift from infectious to chronic and degenerative diseases. In the last decades, emerging and reemerging infectious diseases marked the beginning of the third epidemiological transition, characterized by three main trends: (i) identification of a substantial number of new diseases associated with significant morbidity and mortality in human beings; (ii) an increase in incidence and prevalence of preexisting infectious diseases thought to be under control; (iii) appearance of antimicrobial-resistant strains that are difficult to manage (1). These trends occur within a context of globalization, international trade, migration, and ecological changes that affect the climate and the environmental equilibrium. (B) Major viral pandemics in human history. Smallpox, one of the greatest scourges in human history, first appeared in agricultural communities in northeastern Africa about 10,000 B.C.E, spreading throughout the Old World (2). Smallpox was endemic to Europe, Asia, and Africa for centuries, killing millions of people. Variola virus, caused devastation on native populations because the indigenous populations lacked natural immunity to smallpox, wiping out 90 to 95% of the indigenous people over a century. It is unknown how many people smallpox has killed throughout centuries, but only in the twentieth century, smallpox estimated mortality is of 300 to 500 million people. Smallpox could be eradicated thanks to massive vaccination campaigns (3, 4). The 1918 pandemic influenza (Spanish flu), caused by an antigenically distinct H1N1 influenza virus, occurred in three different waves, starting in March 1918, and waning by the summer of 1919 (5). The virus infected about one-third of the planet's population (~500 million people at that time) and made an estimated 50 million victims. During the 1918 influenza pandemic, the cause of the Spanish flu was unknown; there were no antivirals to treat the disease or vaccines to prevent infection, no antibiotics for therapy of secondary bacterial infections, and no healthcare notion. The main response to the Spanish flu was based on physical and social distancing, isolation, and quarantine. The Spanish Flu marked an inflection point in global health as the concept of socialized medicine emerged and the importance of coordinating public health at the international level was recognized. Since the discovery of HIV/AIDS [beginning of 1980's, more than 77 million people have been infected with this virus, and about 35 million people have died of AIDS (6, 7). To date, around 37 million worldwide live with HIV, of whom 22 million are on treatment. Although there is no cure for AIDS and no vaccines to prevent HIV, HAART can successfully control HIV. The HIV/AIDS pandemic have had a negative influence on the global economy, though Africa, where the highest percentage of HIV/AIDS cases occur, was particularly affected. Developed countries engaged with the developing world to give access to antiretroviral therapy and to establish a health care infrastructure. In December 2019, a cluster of pneumonia cases of unknown etiology was reported in Wuhan City (Hubei province, China) (8, 9). By mid-January 2020, a novel coronavirus, named SARS-CoV-2, was identified as the etiologic agent of this outbreak. The COVID-19 pandemic is not only a health crisis; it affects our society and the economy. The impact of the pandemic will differ from country to country, but at a global scale, it will increase poverty and inequalities, propelling the amount of people living in conditions of extreme poverty in the next decade. COVID-19 is changing the trajectory of development the world had before the emergence of SARS-CoV-2. (C) Examples of newly emerging and reemerging viral diseases in the past decades. The (re)emergence of infectious diseases is mostly the consequence of the changes humans introduced in nature. Most zoonosis have occurred because of an increase contact between human beings with animals, linked to the agricultural revolution of the last decades (10). Bush meat handling and consumption of non-human primates is an effective route for the transmission of zoonotic pathogens into human populations. Several viruses, such as HIV/AIDS (via SIV) and HTLV, associated with leukemia, lymphoma, and myelopathy, have been related to pathogens of non-human primates. Bush meat is also linked to the reemergence of Ebola virus in 2015–2016. Since the 1918–1919 Spanish flu, other less severe influenza pandemics have occurred in 1957 (H2N2 Asian Flu), 1968 (N3H2 Hong Kong Flu), and 2009–2010 (H1N1 Swine Flu) (11). Besides, several epidemics caused by novel...