C.84-AIDS Vaccine Thai RV 144 Correlate Of Protection: Envelope gp120 V2 Loop, Which Induces Protect Imprimer
Écrit par TRAN Guy Mong Ky   
Lundi, 09 Décembre 2013 12:13

C.84-AIDS Vaccine Thai RV 144 Correlate Of Protection: Envelope gp120 V2 Loop, Which Induces Protective Neutralizing IgG Antibodies, Is A Marine Conus Mu-Conotoxin Binding To The Voltage-Gated Na+ Sodium Channel

Présentation Poster au 5°congrès européen de virologie ( Lyon, Septembre 2013)

REF 058         Category: 04. Adaptive immunity and Vaccines

Publié dans Virologie Septembre 2013, vol 17, Supplement S 134


Thai RV 144 vaccine efficacy is 31%; protective IgG target the gp120 V1-V2 loops. We analyse the V2 loop (Zolla-Pazner S, 2013) by Amino Acid (AA) sequences comparison by Basic Local Analysis Search Tool Protein (BLASTP) with visual search and three-dimensional (3D) structures of conotoxin (Xue T, 2003) and spider Atrax atracotoxin (Pallaghy PK, 1997). The 2 Thai vaccine strains V2 loops were screened on toxins binding to the voltage-gated Na  channel (NaCh). Result: 1) 3 mu-conotoxin active site AAs (K13, Q14, K16) (Conus Geographicus, Kinoshitai, Striatus, Betulinus chimera) (Ekberg J, 2008) are found in the Thai V2 loop (V172 crucial):

Hebergeur d'image

Hebergeur d'image

Hebergeur d'image

2) The vaccine MN strain V2 loop mimics the scorpion toxin NH2-terminus active site 1-KKEGY-5 (Kharrat R, 1989); its deletion abolishes the toxicity (El Ayeb M, 1986). Interestingly antibodies against scorpion toxin NH2-terminus 1-KKEGY-5 induce broad cross-reactive protection (Devaux C, 1996). The toxin precursor (Cn II-13, AaH, Bot IX chimera) (Possani LD, 2000) is included.

Hebergeur d'image

Hebergeur d'image

3) V2/V3 loops of HIV-2/SIV PBJ14 (fatal AIDS) were 3D superimposed on spider Atratoxin (Atx)/versustoxin, 2 NaCh ligands. Atrax Robustus is a very dangerous spider from Australia.

V2 loop YxxxWYxxDxxC is conserved in HIV-2.

V3 loop AA sequence is SGLVFH:

Hebergeur d'image

Hebergeur d'image


The scorpion venom concept of AIDS (Tran GMK, 1989, 1993, 1997) is confirmed by the homology between the Thai V2 loop and mu-conotoxin, a NaCh ligand. Omega-3, a NaCh modifier, is efficient in AIDS (Caprani A, 2012). AIDS vaccine should target V2/V3 loop, and avoid mitigating and deleterious IgA directed against the envelope first conserved region C1 (Haynes BF, 2012) (Tran GMK, Eur Conf Virol 2013, Lyon).

An AIDS therapeutic vaccine (as was the case for Pasteur anti-rabies vaccine) would be more rapid to develop, step by step, than a classical prophylactic vaccine: The rapidity of a therapeutic vaccine is calculated in months, whereas for a prophylactic vaccine, each trial would take about a dozen of years. The same therapeutic vaccine, when finally successful, can be then converted in a prophylactic vaccine (following the anti-rabies vaccine example).

The scorpion model of AIDS means that there must at least 6 or 7 different AIDS vaccines, as numerous as the number of different geographical species of scorpions. A mannose-based vaccine must be added to the proteins.




Caprani A , Tran GMK and Roudiere L. Use of new targets (D-Mannose receptor, sodium channel voltage dependent) in a new effective, low cost HAART. Validation with the presentation of a clinical case. 17th Int Symp HIV Emerging Inf Dis (ISHEID) 2012, Marseille. Retrovirology 2012, 9 Suppl 1: P13.  Devaux C, Fourquet P, Granier C. A conserved sequence region of scorpion toxins rendered immunogenic induces broadly cross-reactive, neutralizing antibodies. Eur J Biochem. 1996, 242: 727-35. Ekberg J, Craik DJ, Adams DJ. Conotoxin modulation of voltage-gated sodium channels. Int J Biochem Cell Biol. 2008, 40: 2363-8. Review. El Ayeb M, Darbon H, Bahraoui EM, Vargas O, Rochat H. Differential effects of defined chemical modifications on antigenic and pharmacological activities of scorpion alpha and beta toxins. Eur J Biochem. 1986, 155: 289-94. Haynes BF, Gilbert PB, McElrath MJ et al. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012, 366: 1275-86. Kharrat R, Darbon H, Rochat H, Granier C. Structure/activity relationships of scorpion alpha-toxins. Multiple residues contribute to the interaction with receptors. Eur J Biochem. 1989, 181: 381-90. Pallaghy PK, Alewood D, Alewood PF, Norton RS. Solution structure of robustoxin, the lethal neurotoxin from the funnel-web spider Atrax robustus. FEBS Lett. 1997, 419: 191-6. Possani LD, Merino E, Corona M, Bolivar F, Becerril B. Peptides and genes coding for scorpion toxins that affect ion-channels. Biochimie. 2000, 82: 861-8. Review.  Tran MKG. Homology of HIV 1 gp110 with venoms (scorpion, sea anemone; cobra cytotoxin) whose receptors are ionic channels (Na+ acetylcholine regulated; Ca++). XIX Congress Pediatrics, Paris Jul 1989. Poster M-24. Tran MKG. HIV1 envelope V3 loop mimics scorpion and spider neurotoxins, whose receptor, the Na+ sodium channel, is the target of Tacrine (THA, TetraHydroAminoAcridine). IXth Int. Conf. AIDS, Berlin Jun 1993. Abstr PO-A01-0022. Tran GMK. The scorpion venom model of Aids: Mimicry between anti-V3 loop antibody and the sodium channel the target of Tacrine: A possible vaccine. Europ Aids Clin Soc (EACS), 1997: Abstract 475.  Xue T, Ennis IL, Sato K, French RJ, Li RA. Novel interactions identified between micro-Conotoxin and the Na+ channel domain I P-loop: implications for toxin-pore binding geometry. Biophys J. 2003, 85: 2299-310.  Zolla-Pazner S, deCamp AC, Cardozo T et al.  Analysis of V2 antibody responses induced in vaccinees in the ALVAC/AIDSVAX HIV-1 vaccine efficacy trial. PLoS One. 2013, 8(1): e53629. doi: 10.1371/journal.pone.0053629.

Acknowledgements: Positifs Association.









Mise à jour le Samedi, 28 Décembre 2013 14:36