The face of the unprecedented Ebola epidemic is now unshrouded, stirring up talk of a global crisis and unmitigated calls for medical countermeasures. The medical community is working furiously to respond to this worst-ever outbreak of Ebola but with no approved vaccines or drug treatments, the response is muted. African leaders and the World Health Organization are now calling for use of experimental drugs to combat the spread of Ebola. The past has shown us that humanitarian acts, if not carefully orchestrated and vetted, have the potential to yield unanticipated fallout. Fears in Northern Nigeria of the polio vaccines being linked to a malfeasant conspiracy resulted in resistance to efforts by the World Health Organization to eradicate polio. This form of irrational paranoia could well be validated if experimental Ebola drugs and vaccines are delivered without clear understanding of risks, no matter how well-intentioned the efforts.
As political and public health leaders come together in the coming weeks to address the calamity unfolding in West Africa, attention will focus on the handful of Ebola therapies and vaccines in early stages of testing, and will develop recommendations on which might be useful to squelch the outbreak. Scientific questions that we expect to be raised at this consultation include:
Can the recovery of the two American relief workers from Ebola be attributed completely to the "secret" serum, zMapp, or were these individuals among the fortunate few who were able to fight off the Ebola infection through their normal immune system responses? Examination of these cases in more depth will shed light on the apparent effectiveness of the therapy, and will inform further debate. This is now going on.
Of the Ebola vaccine candidates, one uses an adenovirus (common cold) delivery system. This means that a common virus can be altered to incorporate elements of other viruses to elicit an immune response. In HIV vaccine development, use of the adenovirus delivery system has led to concern by some for its use in regions with relatively high infection rates because in two clinical trials where adenovirus was used to deliver the HIV vaccine candidate, there was an increase in HIV infections in the clinical trials and no protection in any other. (1, 2, 3) This may be because adenovirus may over activate T cells that become new targets for HIV infections. As vaccine candidates are evaluated for Ebola, and in a short turnaround time, scrutiny on risks and benefits of potential vaccine delivery systems is paramount.
In addition, there are highly effective vaccines against other viral diseases, such as hepatitis B, which do not depend on benign viruses to deliver their immune punch. Clumping antigens into a membrane-encased "virus-like particle" is a highly effective vaccination method. Should we scale up this work on these kinds of vaccine candidates to avoid the potential risks from using presumably benign viruses as part of the vaccination development strategy?
As an ethical imperative, those most affected by Ebola must be at the negotiating table as decisions are made about scale-up and rapid distribution of experimental and potentially promising drugs and interventions. In addition to African political and public health leaders, we hope to see significant representation in the negotiations by African medical virologists. In this way, African virologists will be included as pressing policy decisions are made which will affect African communities. And, African virologists will be better positioned to describe actions and outcomes in local languages and in keeping with local norms. When Ebola drugs and vaccines become available, trust -- engendered best by knowledgeable local leaders - may be the vital ingredient in ensuring that drugs are distributed most quickly to those in need.
(1) Hammer et al., N Engl J Med. 2013 November 28; 369(22): 2083-2092; Gray et al., Lancet Infect Dis. 2014 May;14(5):388-396.
(2) Rerks-Ngarm et al., N Engl J Med. 2009 December 3; 361(23): 2209-2220.
(3) Chen et al., J. Virol 2010, October; 10522-10532.