Table 2.

Animal immunizations yielding sera or mAbs that neutralize three or more subtypes

Immunogen Species Neutralization Reference 
Oligomeric electrophilic gp120 Mice mAb which neutralizes 11 strains from subtypes A, B, and C, including tier 2 and 3 isolates, with intermediate potency. Nishiyama et al., 2009  
Multi-subtype (ABC) gp160 DNA immunization + GM-CSF Mice Pooled sera from 6 animals neutralized 1 strain from subtype A and C and 3 strains from subtype B. Rollman et al., 2004  
Synthetic peptide derived from C2 residues 218-239 from CRF01_AE Env Mice mAb neutralizes 10 strains out of 14 tested, including subtypes A, C, D, and AE but not B Sreepian et al., 2009  
Formaldehyde-stabilized, heat-inactivated virion subtype B cytoplasmic tail Env mutant (more Env on surface) Mice Sera from 5 animals neutralized 7 strains from subtypes A, B, C, and AE Poon et al., 2005  
Rabbits Sera from 3 animals neutralized 4 strains from subtypes A, B, C, and AE but less potently than murine sera  
VEE virus replicon expressing: gp140/gp160, gp160 lacking cytoplasmic tail Mice Sera from 6 animals neutralized 8 nonhomologous subtype B, and pooled sera neutralized subtype C and E viral pseudotypes; Dong et al., 2003  
Rabbits Sera from 3 animals neutralized subtype B (SF162) and sera from 2 of these animals also neutralized subtype B (R2)  
Gp140 with novel carbopol-971p and MF59 adjuvant combination Rabbits Sera from 6 animals in the combined adjuvant group neutralized 6 strains from subtypes A, B, and C, 5 of which with superior potency to either adjuvants alone. Lai et al., 2012  
2F5 used to select immunogen from combinatorial libraries of recombinant human rhinoviruses displaying ELDKWA Guinea pigs Sera from 1 animal neutralized 9 strains from subtypes A, B, C, D, and AE with moderate/weak potency Arnold et al., 2009  
Multiclade (A, B, C) gp140ΔCFI DNA (mutations in the cleavage site, fusion peptide, and interhelical regions) followed by replication defective adenovirus expressing gp140ΔCFI Guinea pigs Sera from 4 animals neutralized 13 strains from subtypes A, B, and C with weak potency Chakrabarti et al., 2005  
Gp140 (subtype A or C), verified as homogenous and stable Guinea pigs Sera from animals immunized with either gp140 neutralized 1 subtype A, 2 subtype B, and 4 subtype C strains with statistically higher titers for sera resulting from subtype C gp140 rather than gp120 immunization Kovacs et al., 2012  
Gp120 protein from subtype B Llamas VHH mAb, neutralizes up to 40% of 59 strains tested from subtypes A, B, C, BC, AG, and AE with variable potency. Forsman et al., 2008  
Gp140 proteins from subtypes A and B/C Llamas VHH mAb, neutralizes 70–96% of strains, with 30–100 strains tested from subtypes A, B, C, BC, AG, AE, AC, ACD, D, and G McCoy et al., 2012; Strokappe et al., 2012  
Gp140 Rhesus macaques Sera from 6 animals potently neutralized 5 strains from tier 1 (subtypes B, C, and A) and weakly neutralized 2 tier 2 strains. Protection: modest, nonsterilizing impact on acquisition of heterologous SHIV Sundling et al., 2010  
Immunogen Species Neutralization Reference 
Oligomeric electrophilic gp120 Mice mAb which neutralizes 11 strains from subtypes A, B, and C, including tier 2 and 3 isolates, with intermediate potency. Nishiyama et al., 2009  
Multi-subtype (ABC) gp160 DNA immunization + GM-CSF Mice Pooled sera from 6 animals neutralized 1 strain from subtype A and C and 3 strains from subtype B. Rollman et al., 2004  
Synthetic peptide derived from C2 residues 218-239 from CRF01_AE Env Mice mAb neutralizes 10 strains out of 14 tested, including subtypes A, C, D, and AE but not B Sreepian et al., 2009  
Formaldehyde-stabilized, heat-inactivated virion subtype B cytoplasmic tail Env mutant (more Env on surface) Mice Sera from 5 animals neutralized 7 strains from subtypes A, B, C, and AE Poon et al., 2005  
Rabbits Sera from 3 animals neutralized 4 strains from subtypes A, B, C, and AE but less potently than murine sera  
VEE virus replicon expressing: gp140/gp160, gp160 lacking cytoplasmic tail Mice Sera from 6 animals neutralized 8 nonhomologous subtype B, and pooled sera neutralized subtype C and E viral pseudotypes; Dong et al., 2003  
Rabbits Sera from 3 animals neutralized subtype B (SF162) and sera from 2 of these animals also neutralized subtype B (R2)  
Gp140 with novel carbopol-971p and MF59 adjuvant combination Rabbits Sera from 6 animals in the combined adjuvant group neutralized 6 strains from subtypes A, B, and C, 5 of which with superior potency to either adjuvants alone. Lai et al., 2012  
2F5 used to select immunogen from combinatorial libraries of recombinant human rhinoviruses displaying ELDKWA Guinea pigs Sera from 1 animal neutralized 9 strains from subtypes A, B, C, D, and AE with moderate/weak potency Arnold et al., 2009  
Multiclade (A, B, C) gp140ΔCFI DNA (mutations in the cleavage site, fusion peptide, and interhelical regions) followed by replication defective adenovirus expressing gp140ΔCFI Guinea pigs Sera from 4 animals neutralized 13 strains from subtypes A, B, and C with weak potency Chakrabarti et al., 2005  
Gp140 (subtype A or C), verified as homogenous and stable Guinea pigs Sera from animals immunized with either gp140 neutralized 1 subtype A, 2 subtype B, and 4 subtype C strains with statistically higher titers for sera resulting from subtype C gp140 rather than gp120 immunization Kovacs et al., 2012  
Gp120 protein from subtype B Llamas VHH mAb, neutralizes up to 40% of 59 strains tested from subtypes A, B, C, BC, AG, and AE with variable potency. Forsman et al., 2008  
Gp140 proteins from subtypes A and B/C Llamas VHH mAb, neutralizes 70–96% of strains, with 30–100 strains tested from subtypes A, B, C, BC, AG, AE, AC, ACD, D, and G McCoy et al., 2012; Strokappe et al., 2012  
Gp140 Rhesus macaques Sera from 6 animals potently neutralized 5 strains from tier 1 (subtypes B, C, and A) and weakly neutralized 2 tier 2 strains. Protection: modest, nonsterilizing impact on acquisition of heterologous SHIV Sundling et al., 2010  

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