Thursday, December 11, 2014

Will A Double Dose Ebola Vaccine Be Practical -- In West Africa?

That's an eminently fair question to ask. Of course, J&J, and GSK, both well into development and testing with separate "prime, plus booster" regimens, at present, are arguing that the immunity from a double dosing will be more durable, longer term. I concur that is likely to be true, given past vaccine trial experiences, in other viral outbreaks.

The difficult reality, however, is that the health care system in some of these geographies is so strained, and the people so widely dispersed (without many reliable methods of recall and followup contact), a second dose might never be given in more than three quarters of the population. And that would mean the outbreak would not be contained, at all. Add to this, that J&J's booster component is required to be grown up in chicken eggs -- a notoriously difficult way to acheive the pandemic volumes needed for the booster. [Just ask Baxter about its 2010-2011 era avian flu vaccine experiences, here.]

It is true (as Reuters is reporting) that Merck's trial in Geneva, Switzerland is presently on hold -- while four cases (of 59) of joint pain are evaluated -- to be sure that the malady is temporary, and reversing. Even so -- Merck's vaccine candidate (so far) shows the strongest single dose immune response.

And a single dose regimen may be the only practical way to contain this -- and other -- outbreaks. It is just too hard to do follow-up for second dosings, on vast swaths of rural, low infrastructure, migrant populations. Populations like those now afflicted in West Africa. The UN public health organizations -- and Doctors Without Borders -- have seen this, over and over, again.

So (and all of this is just my opinion), assuming that the joint pain and stiffness is temporary, in the Merck/NewLink Genetics candidate, I think Merck's vaccine will be the one deployed in Sierra Leone, at least this time around. Such temporary stiffness is not all that uncommon a side effect -- of several vaccines, already on market. . . . so we should not be too terribly surprised to see it appear here.

Now, let us hope that it is temporary -- because the alternative candidates present some real logistical nightmares -- in most of Africa -- where they will be most sorely needed.


Birdman said...

Yes, indeed, you are absolutely correct on the nightmare of deploying a 2 dose vaccine during an outbreak in an area with strained health care resources. I see today's press on the 2 dose vaccination as spin introduced by the adenovirus vaccine candidate supporters because they are concerned that their vectors are not immunogenic enough for a single dose regimen.

I have not yet seen human immunogenicity data from the VSV-EBOL candidate so I can not comment about it being more immunogenic than the other candidates. I can guess, based on the nature of the VSV vector, that it will be more immunogenic than the adenovirus vectors.

The minor safety signals seen in the Geneva study are somewhat surprising considering that these have not been reported from the 4 other ongoing VSV-EBOL studies: WRAIR 2163, NIH NIAID Study 15-I-0001 2014, the Nova Scotia study and the Hamburg Study. However the temporary suspension of the study will remain in effect until the PI has had an opportunity to perform follow up testing and observations and to discuss the safety signals with the PI's from the other VSV studies to see if they have similar observations.

Birdman said...

I found more info on other vaccines that have joint pain as a side effect. This does not necessarily indicate there is a problem with a vaccine.

1) Adenovirus vaccine mild side effects stuffy nose, sore throat, joint pain (about 1 person in 6)

2) HPV vaccine mild side effects muscle or joint pain (up to 1 person in 2)

3) MMR vaccine Moderate side effects temporary pain and stiffness in the joints, mostly in teenage or adult women (up to 1 out of 4)

4) Rabies vaccine Moderate side effects hives, pain in the joints, fever (about 6% of booster doses)

5) TDAP vaccine Moderate side effects chills, body aches, sore joints, rash, swollen glands (uncommon).

It was also announced today that a multicenter dose response trial has started recruiting to test the VSV-EBOL vaccine at doses 10^6, 10^5, 10^4 10^3. The Geneva study was testing at 10^7 and 5x10^7.

Birdman said...

Only real news on Ebola vaccines is for the ChAd3-EBOL monovalent study in Lausanne. It seems that fever is more prevalent than what was reported in Ledgerwood 2014 NEJM (20%) and that the monovalent ChAd3 ebola vaccine (Zaire only) is "hotter" than the bivalent vaccine (Zaire and Sudan).

"The safety data looked satisfactory so far," said Professor Blaise Genton, who is leading the GSK trial in Lausanne. "General symptoms such as fever might be slightly more frequent, though no serious adverse event has been observed so far.