The results for the two clinical trials testing the safety and efficacy of the RTS,S vaccine where published in the NEJM at the beginning of this month, coinciding with a keynote presentation at this year’s Trop Med meeting in New Orleans.

Here are the links, but my synopsis and comments are to follow.

Efficacy of RTS,S/AS01E Vaccine against Malaria in Children 5 to 17 Months of Age (Bejon et al, NEJM, 2008 Dec 11;359(24):2521-32)

Safety and Immunogenicity of RTS,S/AS02D Malaria Vaccine in Infants (Abdulla et al., NEJM, 2008 Dec 11;359(24):2533-44.)

I recently read a Nature Immunology article by Denzel et al. on how basophils enhance humoral immunological memory by inducing B cell proliferation and robust and specific antibody responses in a mouse vaccine-infection model. It was interesting because I always thought basophils were rather insignificant in regards to memory immune responses. I never really pay attention to the “basophil” column on the differential of a CBC (usually a meaningless <1%). To me, basophils were somehow involved in allergic and helminth responses and were the peripheral cousin of the mast cell.

But after reading this article, I began thinking of basophils in a whole new light. Primarily because I knew that malaria suffers from a deficient memory B cell response. I’ve thought long and hard about a connection and some nifty experiments to test my hypothesis. However, I won’t divulge much more given that I am still in the proposal mode…

Reference:

Nat Immunol. 2008 Jul;9(7):733-42. Epub 2008 May 30.

-tmt

Simon Draper and his colleagues at Oxford have shown that high-titer antibody responses can be achieved using a viral vector-based immunization regime in the P. yoelii murine infection model. They used a adenovirus human serotype 5/modified virus Ankara prime-boost strategy where they expressed the 42 kDa fragment of MSP-1 from P. yoelii (MSP1-42) on Ad5 and MVA vectors and assess for both cellular and immune responses. By fusing murine complement C4b binding protein (C4bp) to the C terminal end of MSP1-42, they were able to enhance antigen-specific total IgG titers, with a shift towards T helper type 1 (T_H1) associated antigen-specific IgGs (IgG2a, IgG2b and IgG3). Thus, they demonstrated that C4bp can be an effective ‘molecular adjuvant’ in promoting antibody responses in a viral vector–based immunization strategy.

Of note, given the recent disappointing and surprising results of the STEP/HVTN 502 trial, which used an adenovirus human serotype 5 vector to express HIV gag, pol, and nef genes, the NIAID has voluntarily paused several of its current human vaccine trials employing adenovirus-based vectors.

By the time the Draper study makes it to human trials, I am sure the mechanism behind why adenovirus-based vectors increased HIV infection rates in a subpopulation of vaccinees with high pre-existing Ad5 antibody titers will be elucidated.

Here’s the reference on Draper’s study:

Nat Med. 2008 Jul 27. [Epub ahead of print]

PMID: 18660818

-tmt

So, my original plan to compare anti-malarial resistance markers between families/communities who used ITNs and IRS and those that did not had to be scrapped since there were too few malaria cases in Macha, Zambia, where I planned to do the study.

This is from the Director of the Malaria Institute at Macha:

“However, to give you an idea, I can tell you that  the inpatient case load for pediatric malaria in 2008 was the lowest in many years – with a total of only 25 discharged cases of confirmed malaria for April and May of 2008. That compares with 471 discharges for malaria in those same two months as recently as 2003.
The Epi studies being conducted in local village areas by the team under the leadership of Dr Bill Moss at JHSPH, are finding that the prevalence this year of asymptomatic carriers of P falc. is around 5% in the area around Macha.”

This is good for everyone! 

Here’s a link to my original proposal:

The Effect of Malaria Control Policies on the Prevalence of Plasmodium falciparum Drug-Resistant Genotypes and Gametocyte Carriage Rates in Zambia

-tmt

…which is good news. Except that I will probably have to re-think my project since I was expecting on collecting at least 100 malaria-positive blood samples for my analysis.

-tmt

I came across this paper by Jacques Prudhomme and Karine Le Roche (of P. falciparum transcriptome fame) in which they give evidence that a compound derived from the marine actinomycete Salinospora tropica called salinosporamide A inhibits the parasite proteosome and effectively kills P. yoelii yoelii in an in vivo mouse model.

PLoS ONE. 2008 Jun 4;3(6):e2335

-tmt

A recent issue of Science (May 23) titled “Microbial Worlds” had an article on sponges on page 1028. Apparently, multiple, unrelated species of sponges produce a chemical called manzamine A that has anti-malarial properties reported to be more efficient than chloroquine or artemisinin at killing parasites. The chemical is actually produced by a certain bacteria that grows on sponges.

This is the most recent review I found:

Curr Pharm Des. 2007;13(6):653-60

Here’s a NYT article about os indios in Acre State, Brasil.

If finished the first draft of my Zambia project proposal–now I have to figure out where to submit this thing to get some funding.

I will put a link to the PDF up soon.