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

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):

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.

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:

CONCLUSION

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 directd against the envelope first conserved region C1 (Haynes BF, 2012) (Tran GMK, Eur Conf Virol 2013, Lyon).