The recent large scale outbreak in Sierra Leone and Liberia has taught that we should be ready and well-prepared for such epidemics in future. In my opinion, progress should be made on two fronts: 1) diagnostics 2) vaccination. If infections can be identified earlier, and ring vaccination can be implemented well on time, it is possible to curtail the spread of infections. As for your question on knowing the infection better before vaccine trials, I guess it is a complicated question. How much should be known? I believe, that vaccines in question are in clinical trials because they are already validated using various infection systems (for example cell culture and small animal models if they exist for ebola virus) and found promising. so in my opinion, It is not very prudent to keep waiting until every nitty gritty of the virus is known. However, I am very curious to know what others think. 

The current vaccine candidates for Ebola are developed long back with no takers for further vaccine trials.  I wish we had a vaccine before this out break started. We could have avoided suffering and deaths.

Basically, vaccine trials are to confirm safety and efficacy of the vaccine on a limited number of volunteers. Unlike animal vaccines, no virus challenge studies are feasible in Human and hence vaccine trials are done in the face of out breaks or in endemic areas. I feel it is essential to complete the trials  as early as possible for a disease like Ebola.  

Well-designed vaccine trials always have specific questions they are designed to answer. You need to know enough about the disease to be able to formulate those questions, but you don't need to know everything about the disease to be able to interpret the results.

In the case of Ebola, the two different trial designs were intended to answer two questions. First, if you are exposed, can vaccination reduce your risk of illness or death? Second, can vaccination of potential contacts prevent the spread of the disease?

Because the vaccines were tested as the number of cases were falling (due to better control of infection) we did not get an answer which is 100% reliable - because there were fewer cases overall. But the data does very strongly suggest that the answer to both questions is yes. That's good enough to know that we should deploy vaccination in an outbreak situation.

So it was worth testing the vaccines, even though when the trials were designed, we did not know about recurrent infection in humans. In the end, it is death and disease that we aim to prevent by vaccination. What our new knowledge adds is that people who are exposed or who fallen ill with Ebola need to be followed up.

In any future outbreak, we also need to test whether vaccinated people can still get a latent infection. From what we have seen, vaccination will probably prevent latent infection but again, but even if it didn't, we would still vaccinate. After all what would you rather have - a latent infection which apparently has a much lower risk of spreading and causes some long-term side effects, or full-blown Ebola infection that is highly infectious and fatal 50-80% of the time?

We don't need to know everything about the disease to know which outcome is preferrable!

Thanks Timothy...your reasoning sounds good. so the big question now is  how much is enough:                                                                                                                                         You need to know enough about the disease to be able to formulate those questions, but you don't need to know everything about the disease to be able to interpret the results.

because vaccine in and for itself constitute another epidemic problem should its components goes into wild or ended up creating a whole new problem health wise.

 I do agree with the comments of Mohsan Saeed and Timothy Mark Doherty The advancement in the diagnostic procedure like, it should be quick reliable specific to confirm the infection due to Ebola. The other task is an improvement in  the efficacy of vaccine (safe and provide protection at least more than 80%).Moreover, the use of high immune sera for sero conversion as used for the recovery of a Lady Health worker who was taking care of the Ebola patient and got seriously ill due to Ebola infection. Recently there was news of her sickness due to Ebola infection. 

These recurrent infection cause complex situation to deal with the virus. The surveillance of the disease in the endemic areas should be mandatory until a  successful vaccination program may be formulated, Moreover, 1) the production and availability of purified gammaglobulins against Ebola virus is important for immediate recovery.2) Availability of diagnostic test for the latent infection and 3) preparation of vaccine can be recommended in the presence of latent infection. However, the funding for technical assistance and   implementation of  these task in the field  will be required by the world donor agencies on short term and long term basis.

Jia, it's essentialy impossible for the vaccines to creat a new epidemic, or "go wild" since none of the vaccines tested in humans contain ebola virus.

No no is my answer .

Paras Pokharel can you please explain why you are saying no no? 

It depends on what you mean by "not much is known". In the case of ebola,  there is a lot we don't know about immunity and recovery in humans, and virus-host relationships in animal reservoirs. However, what we do know is that it causes a deadly disease in humans, that outbreaks occur fairly regularly in some endemic areas (e.g. central Africa), and that outbreaks can occur on a large scale and cause major public health and economic disruption.  The unpredictable nature of ebola outbreaks mean that prospective clinical trials are extremely difficult to carry out. The nature of the disease means that running a large scale clinical trial in the throes of an outbreak is similarly difficult and could possibly distract from the urgent control response needed to bring the outbreak under control. Consequently, if a clinical trial protocol can be developed that allows medical authorities to gain information that can be of immediate use in the event of another outbreak, then it is worth doing. The investment has already been made in developing the vaccines - it would be extremely unfortunate if we now pass on the opportunity to evaluate them. It is almost certain that they will be needed in the future in endemic areas.

With respect to the safety of the vaccines, none of the vaccines under development is based on live ebola virus, so there is no possibility of them causing ebola. If someone who has recovered from ebola subsequently tested positive for ebola, it means that they had not fully cleared the virus from their body - we already know that it can take a long time for the virus to clear from certain sites like the eye, and male testes. If the person was vaccinated after they had recovered from their initial disease, I would not expect that to have an effect on the length of time it takes for the virus to be completely cleared from their system, because the immunity induced by recovering from the disease will be very strong, and is likely to be stronger than the immunity induced by the vaccine. The vaccines (if they work), will be strong enough to prevent disease, but still not as strong as natural immunity induced by recovering without a vaccine. The fact that so many don't recover is indicative of how strong the immune response must be in those that do.

Best wishes,

David

I agree with the comments from Mohsan Saeed, Panduranga Rao, Timothy Mark Doherty and David Ulaeto in developing vaccines asap without knowing all details about the infection and pathogenesis of the disease. I am not repeating what has already been  discussed. Enough information has been available on the infection and pathogenesis of Ebola. The recurrence of the disease, in general, could be due to inadequate immunity after disease, short term protection or emergence of new strains. Development of vaccines at an early stage will definitely help in protection of the disease and will also provide information to improve upon the vaccines.

I agree with Doherty.  You cannot study Ebola like you study typical diseases: it's not at all predictable it disappears for decades, appears in a small village and nearly instantly kills up to 90% of the people that contract it, then disappears again.   You can't design a study around a disease such as Ebola: you can't predict an outbreak and we don't understand it's vector(s).   When this outbreak occurred we had very little information but it was clear that we had to stop the outbreak from spreading. We had a few experimental vaccines with limited data and some treatment options.  So we used every tool we had and we did the right thing.