In my last 2 blog posts, I have been talking about how hard the researchers are trying to develop a vaccine (includes both humoral and cellular immunity based vaccines). Though many approaches have failed to demonstrate a high level protection, and the scientists have reached a point of frustration, we have reached a time scale where, we are on the verge of development of novel strategies. HIV is probably one of those pathogen, that has defied the science, with the challenge still up in the air for anyone willing to catch it.
|Fig 1: HIV intervention|
In the last couple of weeks there has been some remarkable papers in this field, and i just want to put a very brief summary of these, as most of the ideas pertaining to these, I have discussed somewhere in my previous posts.
bnAb (Broadly neutralizing Antibodies), has come up as a great deal of interest, especially in case of HIV and Influenza, where there is too much of antigenic variation, to attack using a single type of antibody. One of the well studied antibody is 4E10, is probably the neutralizing antibody with maximum spectrum binding known, recognizing a highly conserved epitope in the membrane-proximal region of gp41. Another well studied is b12 which overlaps the CD4 receptor-binding site (CD4bs) on gp120. Now the researchers from The Scripps Research Institute (TSRI) have shown that the 4E10, which has been of great promise, is also reactive against self antigens (Probably through cross reaction), whereas b12 is not. David Nemazee, a senior author said. "It's still possible that we could safely elicit the 4E10-like antibody in order to protect against HIV, We just have to think about how to generate the best antibodies without causing other problems. We have a lot of questions. And now we have a good model to help us answer them". Source
|Fig 2: Ciclopirox|
|Fig 3: DAVEI activity|
Doyle-Cooper C, Hudson KE, Cooper AB, Ota T, Skog P, Dawson PE, Zwick MB, Schief WR, Burton DR, & Nemazee D (2013). Immune Tolerance Negatively Regulates B Cells in Knock-In Mice Expressing Broadly Neutralizing HIV Antibody 4E10. Journal of immunology (Baltimore, Md. : 1950), 191 (6), 3186-91 PMID: 23940276
Hanauske-Abel, Hartmut M. (2013-09-23) Drug-Induced Reactivation of Apoptosis Abrogates HIV-1 Infection. , 8(9), e74414. DOI: 10.1371/journal.pone.0074414
Contarino M, Bastian AR, Kalyana Sundaram RV, McFadden K, Duffy C, Gangupomu V, Baker M, Abrams C, & Chaiken I (2013). Chimeric Cyanovirin-MPER Recombinantly Engineered Proteins Cause Cell-Free Virolysis of HIV-1. Antimicrobial agents and chemotherapy, 57 (10), 4743-50 PMID: 23856780