The Lancet – On Sept 1, the pharmaceutical company Sanofi Pasteur announced that it was withdrawing from development of a vaccine against Zika virus infection. This announcement raises concerns about the future of Zika virus vaccine development, at a time when the number of cases is falling and other questions about the virus remain unanswered.
The Sanofi Pasteur decision came about 2 years after doctors in the Northeast Region of Brazil began to notice an increase in the number of cases of babies born with microcephaly and other congenital defects, the cause of which has since been attributed to a Zika outbreak that has swept through parts of the Americas. Circulation of the virus in Brazil, the country with the highest number of cases, was confirmed in May, 2015. In November of that year, Brazil declared a national public health emergency in the face of a rising number of Zika-associated microcephaly cases. Subsequently, WHO declared the Zika virus outbreak a Public Health Emergency of International Concern between February and November, 2016. From 2015 until the end of August this year, Brazil reported 231 725 suspected cases of Zika virus infection and 137 288 confirmed cases, with 2869 confirmed cases of Zika virus congenital syndrome. However, probably because of population-level immunity, the incidence of new infections has declined from the middle of 2016: there were 7911 cases in Brazil from January to April this year compared with 170 535 in the same period last year. As a result, Brazil declared an end to the national emergency in May this year. Similarly, the USA—a major potential market for a Zika vaccine—reported 5102 symptomatic cases in US states (224 locally transmitted) and 36 079 in US territories (American Samoa, Puerto Rico, US Virgin Islands; 35 937 locally transmitted) in 2016, versus 225 (none locally transmitted) and 554 (all locally transmitted), respectively, from Jan 1 to Aug 30, 2017.
Sanofi Pasteur was the only major pharmaceutical company working on a vaccine against Zika virus, and its decision to withdraw is unsurprising at a time when the number of cases is low and the market seems uncertain. Nevertheless, there is still plenty of activity around vaccine development. WHO reported 40 candidate vaccines in development in January this year, and the WHO Vaccine Pipeline Tracker currently lists 12 phase 1 clinical trials involving six of these. Five of the phase 1 trials are due to be completed between now and the middle of 2018, so results should start to be reported next year. But, assuming the vaccine candidates show promise, who will support further clinical development? The assurance of finance from public funds may well be necessary to attract the interest of major pharmaceutical company partners.
Because of unanswered questions about the epidemiology of Zika virus disease, the target population for a vaccine remains uncertain. Would it be given in childhood, in the same way that children are immunised against rubella virus to prevent transmission and damaging congenital infections when girls grow up to be mothers, or would it be offered to people intending to travel to Zika affected areas? To address this question we need to understand why substantial geographical variations between the incidences of Zika virus infection and Zika-associated congenital defects have been observed.
Brazil recorded a higher incidence of Zika-associated congenital syndrome than did Colombia and Venezuela (which reported no cases), but the latter two countries reported higher incidences of suspected and confirmed Zika virus cases. And within Brazil, at least 80% of cases of Zika-associated congenital syndrome occurred in the Northeast Region. Whether these discrepancies are due to reporting biases or possible cofactors such as previous exposure of mothers to dengue virus or yellow fever vaccine remains the subject of ongoing research. Coming up with recommendations for appropriate populations for receipt of Zika virus vaccines will be challenging without the results of these investigations.
The WHO Zika Strategic Response Plan, published in June, 2016 and due to run until December this year, outlines research priorities. However, illustrating the lower priority that Zika virus is now receiving, the last “quarterly” update of the plan was published a year ago. Now is the time to take a long-term view of Zika research, as we have written before. Zika epidemics will likely reoccur as new vulnerable populations are exposed to the virus. We would best be prepared for this situation by having available vaccines that can quickly be rolled out to the people who need protection.
For WHO Vaccine Pipeline Tracker see
For Zika Strategic Response Plan see
For more on the long-term view of infectious diseases emergencies see Editorial Lancet Infect Dis 2016; 16: 1305