The First Successful Malaria Vaccine
Making a vaccine against a parasite is more complex
than against bacteria or a virus. Joe Cohen, scientist at Glaxo Smith
Kline, who has been in search of a vaccine against the ubiquitous malaria
parasite for 23 years, could testify to this. It could also explain why
there were tears in the eyes of the team when results of the large scale
trial of the most successful vaccine against malaria so far came out.
"It’s been a long time coming, and indeed we are still
not there yet, but it is becoming increasingly clear that we really do
have the first effective vaccine against a parasitic disease in humans."
says Nicolas White, in a recent editorial in the NEJM. WHO has indicated
that if all goes well the RTS,S/AS01 Plasmodium Falciparum malaria
vaccine should be available for use in 3 years. RTS,S/AS01 is a hybrid
construct of the hepatitis B surface antigen fused with a recombinant
antigen derived from part of the circumsporozoite protein derived from the
sporozoite stage of the parasite. The success of Cohen’s vaccine lies in
its ability to stimulate the immune system with several molecules for a
multi-pronged attack and the proprietary adjuvant AS01.
The NEJM has just published an interim report of a
large, multicenter phase 3 trial of this vaccine in which 15,460 children
in two age categories — 6 to 12 weeks and 5 to 17 months — were enrolled.
There was a 55% reduction in overall episodes of clinical malaria and a
35% drop in cases of severe malaria. Inexplicably there was an increased
incidence of bacterial meningitis in the cases who received the vaccine
and this needs further observation. It still remains to be seen how long
the protection lasts especially with declining malaria transmission (NEJM
October 8, 2011).
The Nobel Prize for Medicine 2011
The Nobel Prize in Medicine goes to 3 scientists who
have uncovered the secrets of how organisms sense attack by microbes and
activate innate immunity initially and adaptive immunity later.
Jules Hoffman was working in The University of
Strausburg, France on how fruitflies combat infections. When he infected
them he found that flies who had mutations in a gene named Toll,
all died. Toll mutants died because they could not mount an
effective defense. He concluded that the product of the Toll gene
was involved in sensing pathogenic microorganisms and Toll
activation was needed for successful defense.
Across the Atlantic, Bruce Beutler in the University of
Texas, Dallas, was working from a different angle. He was trying to
understand how lipopolysaccharide (LPS) which is a bacterial product,
sometimes causes septic shock. Mice resistant to LPS had a mutation in a
gene that was quite similar to the Toll gene of the fruit fly. This
Toll-like receptor (TLR) turned out to be the elusive LPS receptor.
When it binds LPS, signals are activated that cause inflammation and, when
LPS doses are excessive, septic shock ensues. These findings showed that
mammals and fruit flies use similar molecules to activate innate immunity
when encountering pathogenic microorganisms.
The third person to share the Nobel this year was Ralph
Steinman of the Rockfeller University, New York. There was intense
speculation whether the award would be withdrawn since he died 2 days
before the announcement of the award. However the Nobel Committee got to
know of it 3 hours after the award announcement. So although the Nobel
Prize is never awarded posthumously, this time the honor has not been
withdrawn. It is tragic that Steinman died battling pancreatic cancer for
which his life had been extended using immunotherapy of his own design.
Steinman discovered the dendritic cell and speculated that it had a key
role in activating T cells. In cell culture experiments he showed that the
dendritic cell is responsible for developing an immunological memory
against various substances which on later encounters will induce an
exaggerated response by T cells. This interesting cell is also involved in
decisions regarding mounting attacks on self and non self antigens (Scientific
American 3 October 2011).