NIAID-DVI: Systems Vaccinology -- Bali Pulendran

Blog Series: NIAID-DVI

So as I stated in an earlier blog...some things flew well above my head at this meeting so some of these blogs will be a re-print of the abstract and some general links and thoughts as well as a load of definitions and attempts to understand the components that made up said persons abstract with a healthy dose of trying to understand what they do. Also some of the presentations drove me to take lots of notes from which I could draw on while others, I'll admit my eyes glazed over...and the only note I wrote (several times on many talks was)

"Crash Course Immunology?"

It actually became a bit comic with how many presentations I wrote that on. I now have a new found appreciation for what immunologists do AND a new understanding of why I don't do it. So kudos to all vaccinologists and immunologists everywhere!

NIAID-DVI: Sanofi CYD dengue vaccine--Where do we go from here? Jean Lang and Bruno Guy

Blog Series: NIAID-DVI

Sanofi Pasteur CYD dengue vaccine programme update

Jean Lang
Sanofi Pasteur

and

Immunological characterization of the Sanofi Pasteur dengue vaccine candidate: hypotheses and investigations to explain results of the Phase IIb proof of concept efficacy trial in Ratchaburi
Bruno Guy
Sanofi Pasteur

So by way of quick review:

credit: Roehrig's Presentation

• the CYD-TDV vaccine is a yellow fever backbone with the prM and E genes replaced by each of the dengue serotypes.
• There was good response in efficacy trials to dengue 1, 3 and 4 however the vaccine failed in illiciting a response to dengue 2 (response was about 30%) DESPITE having satsifactory PRNT titers...see previous blog post.
• In 2012 there was a Phase IIb efficacy trial in Ratchaburi, Thailand
• It showed the vaccine was safe.
• It showed that it was possible to make an efficacious vaccine against dengue
• It raised questions on the reference PRNT assay
• It challenged some of the dengue vaccine development hypotheses
• It reminds us how complex the disease is

NIAID-DVI: TV003 live attenuated tetravalent dengue vaccine -- Stephen Whitehead

Blog Series: NIAID-DVI

Safety and immunogenicity of the NIH live attentuated tetravalent dengue vaccine candidate TV003

Stephen Whitehead
National Institutes of Allergy and Infectious Diseases, NIH

January 13, 2013, the NIH releases a news statement: NIH-developed candidate dengue vaccine shows promise in early-stage trial where they discuss the new vaccine for dengue that has done well in an early stage clinical trial, the study having been published in the Journal of Infectious disease 17 January 2013. Unfortunately the article is behind a paywall...curses!!! So I will do my best to convey what I can through other numerous links and information garnered from pillaged internet slides about the vaccine and of course what I learned in the meeting.

Falling back on John T. Roehrig's presentation because it's such a nice clear presentation...here is the make up TV003.

NIAID-DVI: DENVax -- Jorge E Osorio

Blog Series: NIAID-DVI

Pre-Clinical and clinical development of recombinant live attenuated tetravalent dengue vaccine (DENVax)
Jorge E Osorio
Takeda Vaccines

So Takeda Vaccines took over Inviragen and have been developing a tetravalent, live attenuated dengue vaccine called DENVax. It consists of a molecularly characterized, attenuated DENV-2 strain and three chimeras. The chimeras all have the backbone of the attenuated DENV-2 strain, but the prM and E genes have been swapped out with DENV-1, DENV-3 and DENV-4.

DENVax design from Osorio et al., 2011.

NIAID-DVI --A Preamble: The Sanofi Dengue Vaccine Failure (Chimerivax)

Blog Series: NIAID-DVI

A preamble: The Sanofi dengue vaccine failure, ChimeriVax

So given I am not daily entrenched in the world of vaccine development, the most that I ever heard about dengue vaccines was that there were several out there in development and Sanofi's was the furthest along. Then I heard the Sanofi vaccine failed. It illicited good response to dengue 1, 3 and 4 and did a fantastic fail on dengue serotype 2.

I could end this blog there but my curiosity and incessant need to comb the internet and literature revealed just how 'fantastic' of a fail this was: