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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 (TH1) 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]
-tmt
