Table 1.

Genetic characteristics of HIV-1 broadly neutralizing monoclonal antibodies

Viral Epitope	Antibody binding characteristicsa	Antibody clonal family	Year Published	Isotype and subclassb	Heavy chain V-gene	Light chain V-gene (K or L)	CDRH3 length (Kabat AA)c	VH mutation (nt %)d	VH mutation (AA %)d	Neutralization Breadthe	Neutralization Potencyf	Polyrectiveg	References
MPER of gp41	contiguous sequence	2F5	1993	IgG3	2-5	K1-13	22	14	15	++	++	yes	53, 65, 66, 77, 85
	contiguous sequence	4E10	1994	IgG3	1-69	K3-20	18	14	20	++++	++	yes	53, 65, 66, 76, 85
	contiguous sequence	M66.6	2011	NR	5-51	K1-39	21	4.3	10	+	++	yes	120
	contiguous sequence	CAP206-CH12	2011	IgG1	1-69	K3-20	15	12	19	+	++	yes	115
	contiguous sequence	10e8*	2012	IgG3	3-15	L 3-19	20	21	26	++++	+++	no	110
V1V2-glycan	peptido-glcyan	PG9, PG16	2009	NR	3-33	L2-14	28	12-13	17 - 20	+++	+++	no	82
	peptido-glcyan	CH01 - 04	2011	IgG1	3-20	K3-20	24	14 - 17	23 - 29	+	++	nog1	109, 170
	peptido-glcyan	PGT 141-145	2011	NR	1-8	K 2-28	31 - 32	12-18	21 - 29	+++	+++	NR	83
Outer domain glycan	glycan only	2G12	1994	IgG1	3-21	K 1-5	14	21	32	+	++	NR	53, 65, 75
V3-glycan	peptido-glycan	PGT121-123	2011	NR	4-59	L 3-21	24	17 - 21	21 - 27	++	++++	NR	83
	peptido-glycan	PGT125-131	2011	NR	4-39	L 2-8	19	15 - 23	23 - 33	++	++++	NR	83
	peptido-glycan	PGT135-137	2011	NR	4-39	K 3-15	18	17 - 20	25 - 29	+	++	NR	83
CD4 binding site	CDRH3 loop	b12	1994	NR	1-3	K 3-20	18	13	20	+	++	nog2	53, 64, 78
	no liganded structure	HJ16	2010	NR	3-30	K4-1	19	15	37	+	++	NR	116
	CDRH3 loop	CH103 - 106	2013	IgG1	4-59	L 3-1	13	14 - 16	22	++	++	yesg3	118
	mimics CD4 via CDRH2	VRC01 - 03	2010	IgG1	1-2	K 3-20#	12-14	30 - 32	40-48	++++	+++	no	84, 119
	mimics CD4 via CDRH2	VRC-PG04, 04b	2011	IgG1	1-2	K 3-20	14	30	38-39	+++	+++	no	114
	mimics CD4 via CDRH2	VRC-CH30 - 34	2011	IgG1	1-2	K1-33	13	23 - 24	36-40	+++	+++	no	114, 170
	no liganded structure	3BNC117, 3BNC60*	2011	NR	1-2	K1-33	10	27	37-40	+++	+++	yesg4	117
	mimics CD4 via CDRH2	NIH45-46*	2011	IgG1	1-2	K 3-20	16	30	41	++++	+++	yes	117, 125
	no liganded structure	12A12, 12A21*	2011	NR	1-2	K1-33	13	23 - 25	38-40	++++	+++	yes	117
	no liganded structure	8ANC131, 134*	2011	NR	1-46	K 3-20	16	27	37-38	+++	++	yes	117
	no liganded structure	1NC9, 1B2530*	2011	NR	1-46	L 1-47	16 - 19	24 - 26	36-38	+	++	yes	117

^aMajor binding characteristics indicated by co-crystal structural analysis. mAb 2G12 utilizes unusual domain swap structure - see indicated references. mAb b12 was isolated from phase display library and natural light chain pair was not retained; b12 displays heavy chain only binding in co-crystal structure with gp120.

^bIsotype indicates the natural isotype and subclass of the isolated antibody. In some cases, this was not reported. In many cases, the PCR amplified heavy and light chain genes are expressed in an IgG1 expression vector even though the natural antibody was a different subclass.

^cReported CDRH3 lengths are often based on IMGT or Kabat nomenclature. The Kabat definition is generally used for structural studies and is often 2 AA residues shorter than the IMGT definition. For explanation of the differences in nomenclature, see www.imgt.org.

^dThe percent mutations (nt) of an antibody heavy chain are based on comparison to the inferred germline gene. Percent mutations are sometime also reported based on translated AA sequences (AA).

^eNeutralization breadth is indicated for antibodies tested on large panels of > 100 tier 2 Env-pseudoviruses and the values shown are the percent of viruses neutralized at an IC50 of < 50 ug/ml. ++++ = > 90%; +++ = 75 - 90%; ++ = 50 - 74%; + = < 50%. If there are several members of a clonal family, the broadest clonal member was used.

^fNeutralization potency indicated by median or geometric mean IC50 (ug/ml) of neutralized viruses (i.e. excluding non-neutralized viruses); ++++, IC50 < 0.05; +++ , IC50 = 0.05 - 0.49; ++, IC50 = 0.5 - 4.9; +, IC50 = 5.0 - 50.

^gPoly or self reactivity as assessed by a combination of common autoimmune assays, including cardiolipin ELISA, Hep2 cell IFA and Athena assay for antinuclear antibodies.

^g1One antibody in this clonal lineage, CH103 is polyreactive.

^g2Some have found b12 polyreactive, but studies in b12 VHDJH + VLJL knock-in mice have demonstrated the degree of polyreactivity for this antibody is not sufficient to predispose these antibodies to tolerance deletion (D. Nemazee, personal communication).

^g3CH103, CH104, CH106 are autoreactive, CH105 is not autoreactive.

^g43BNC117 is reported to 3y polyreactive, but not 3BNC60.

^*Additional members of the clonal family also reported in the primary publication. NIH45-45 is same donor and clonal family as VRC01. For mAbs 1NC9 and 1B2530, neutralization data only available for 1B2530

^#VRC01 and 02 were initially reported to derive from inferred VK3-11, but additional analysis of the antibody lineages strongly suggests VK3-20. Also, VRC03 was initially inferred to be from different clonal family than VRC01, but more detailed analysis suggests that VRC01, 02 and 03 are clonal relatives (J. Mascola, P. Kwong, unpublished data)

Notes: NR, not reported.