The International Society for Vaccines is an organization that engages, supports, and sustains the professional goals of a diverse membership in all areas relevant to vaccines - 2017 ISV Annual Congress

POINTS OF VIEW AUG 2015

Title:Challenges in developing vaccines against emerging virus infections

By - Adolfo García-Sastre (ISV President), Icahn School of Medicine at Mount Sinai

While vaccination is the best way to prevent infectious diseases, development of emerging virus vaccines represents a major challenge. The unpredictable nature of emerging viruses, such as MERS, Ebola or pandemic influenza, makes impossible to conduct efficacy trials, as the location and magnitude of the outbreaks, as well as of the specific virus strain causing it, are extremely difficult if not impossible to predict before their emergence. On the other hand, once an outbreak emerges, there is no time to conduct controlled efficacy trails in order to deploy an effective vaccine on time to contain the outbreak.

The 2009 pandemic influenza virus provided with one example of the problems associated with vaccines against newly emerging viruses. Such influenza virus originated from a swine H1N1 influenza virus strain and it was detected in humans only after it was already widely disseminated in Mexico. The outbreak extended quickly to US and the rest of the world, and by the time a pandemic H1N1 vaccine was available and started to be used, the pandemic outbreak had already reached peak infections, and influenza infection cases were in decline. Thus, the vaccine was unable to impact the magnitude and severity of the first wave of infections. Fortunately, this pandemic influenza virus did not cause a large number of severe and lethal human infections, as in the case of previous influenza virus pandemics. Nevertheless, many human lives were lost that could have been prevented by vaccination, if a vaccine would have been available at earlier times.

The lack of a timely vaccine has also hampered the control of the recent ebolavirus outbreak, which is still ongoing although at a lower magnitude, and has devastated the public health system and the economy of several Central West African countries, with more than 10,000 human lives claimed. Previous ebolavirus outbreaks were characterized by high mortality but small number of geographically confined humans cases in remote and underpopulated areas in Central Africa. The virus is thought to jump from a bat reservoir into humans where it undergoes human to human transmission mainly due to contact with infectious body fluids. While ebolavirus human transmission is quite ineffective as compared to other acute and established human virus infections, it was generally accepted that sooner or later, an outbreak would reach one or more larger cities in Africa, where containment would be more difficult and the number of cases would be several orders of magnitude higher. Despite that, the development of ebolavirus vaccines has been a very slow process, due to low priority and to the challenges associated with licensing a vaccine with only animal model data in the absence of (impossible to conduct unless a major outbreak occurs) efficacy trials in humans. The recent outbreak, while boosting the speed and resources put into ebolavirus vaccines, has not been contained by vaccination, as vaccines with proven efficacy in animal models were not available for human use on time.

MERS coronavirus infections in humans have first been described in 2012. This virus in now known to be endemic in several Middle East countries, and human infections likely involves camel to human and human-to-human transmission. MERS disease is a clear reminder of the SARS coronavirus outbreak, both diseases caused by a zoonotic coronavirus that induces acute respiratory syndrome infections in humans, and with the ability to spread from human to human. Although concerns were raised about the potential impact of this virus in humans in the near future, MERS vaccine development has been impaired by the lack of appropriate resources given to this, and the constrains associated with the development of animal models and the lack of a clear path to licensure in the absence of clinical human efficacy trials, which are not possible to be conducted due to the low number of current human infections. The recent outbreak of imported MERS in Korea in the absence of a human MERS vaccine reminded us once more of what these emerging viruses can cause and how much time is lagging behind effective vaccines that can contain these outbreaks.

Pandemic influenza, Ebola and MERS are just three examples of predictable outbreaks for which experimental preclinical vaccines are available, but which lack of a rapid path to approval for human use, a step that is necessary for vaccines to make and impact in future and potentially more devastating outbreaks. Let’s not wait for one more outbreak to realize the need for a different strategy that allows for a more rapid deployment of vaccines against emerging and zoonotic viruses.