Vaccinal antibodies: Fc antibody engineering to improve the antiviral antibody response and induce vaccine-like effects

Figures & data

Figure 1. The structural insights of the complete structure of IgG antibody. (A) Heavy chains are in blue, while light chains are in green and red. Glycosylation location is in white and light orange. PDB entry 1IGY. (B) surface IgG structure by domains: variable fragment (Fv), antigen-binding fragment (Fab) and fragment crystallizable region (Fc). PDB entry 1IGY. (C) IgG Fc domains: CH2 in green and CH3 in blue. Glycosylation site in light gray. PDB entry 1FC1.

Table 1. Human vaccines that induced Fc effector functions and produced protection or reduced the infection risk. Abbreviations: Human cytomegalovirus (HCMV)

Infectious agent	Vaccine	Fc Effector Functions	Reference
SARS-COV-2	ChAdOx1 nCov-19	Antibody-dependent neutrophil/monocyte phagocytosis, complement activation and NK cells activation	^Citation75
	mRNA BNT162b2	Antibody-dependent cellular cytotoxicity (ADCC)	^Citation81
Malaria	RTS, S/AS01	Engagement of FcγRIIA, Antibody-mediated phagocytosis (ADCP)	^Citation82
Tuberculosis	ID93 + GLA-SE	Antibody-dependent phagocytosis (ADCP) NK cell activation Antibody-dependent cellular cytotoxicity (ADCC)	^Citation78
HCMV	gB/MF59	Antibody-dependent cellular cytotoxicity (ADCC) Antibody-dependent cellular phagocytosis (ADCP)	^Citation83
HIV	RV144	Antibody-dependent complement activation Antibody-dependent cell-mediated cytotoxicity (ADCC)	^Citation84–86

Table 2. The effect of Fc engineering by inserting mutations. Mutation named as S298A means Serine was mutated to Alanine. Residues numbering is based on EU numbering system

	Fc mutations	IgG isotype	Effector Function	Mechanism of Action (MOA)	Reference
Fc mutations for enhanced	S298A/E333A/K334A (AAA)	IgG1	ADCC	↑ FcγRIIIA	^Citation94
effector functions	S239D/A330L/I332E (DLE)	IgG1	ADCC	↑ FcγRIIIA	^Citation111
	F243L/R292P/Y300L/V305I/P396L (LPLIL)	IgG1	ADCC	↑ FcγRIIIA, FcγRIIA	^Citation89
	L235V/F243L/R292P /Y300L/P396L (VLPLL)	IgG1	ADCC	↑ FcγRIIIA, FcγRIIA	^Citation90
	G236A/A330L/I332E (GAALIE)	IgG	ADCC	↑ FcγRIIA, FcγRIIIA	^Citation120,Citation121
	G236A/S239D/A330L /I332E (GASDALIE)	IgG	ADCC	↑ FcγRIIIA, FcγRIIA	^Citation113
	In one heavy chain: L234Y/L235Q/G236W/S239M/H268D/D270E/S298A In the opposing heavy chain: D270E/K326D/A330M/K334E	Asymmetrically engineered antibody Fc variant (Asym-mAb1)	ADCC	↑ FcγRIIIA, FcRIIA	^Citation122
	G236A	IgG1	ADCP	↑ FcγRIIA	^Citation110
	G236A/S239D/I332E (ADE)	IgG1	ADCC ADCP	↑ FcγRIIIA, FcγRIIA	^Citation110
	S239D/I332E (DE)	IgG1	ADCC ADCP	↑ FcγRIIIA	^Citation111
	S267E/H268F/S324T (EFT)	IgG	CDC ↓ADCC, ↓ADCP	↑ C1q affinity ↓ FcγRIIIA	^Citation116
	H268F/S324T (FT)	IgG	CDC ↑ ADCC, ↑ADCP	↑ C1q affinity ↑ FcγRIIA ↑ FcγRIIIA	^Citation116
	E345R/E430G/S440Y (RGY)	IgG	CDC	↑ C1q affinity Hexamerization	^Citation49,Citation123
	E345R	IgG	CDC	↑ C1q affinity Hexamerization	^Citation49
	K326W/E333S	IgG	CDC	↑ C1q affinity	^Citation117
Fc mutations for enhanced serum half-life	M252Y/S254T/T256E (YTE)	IgG1	Extended half-life	↑ FcRn affinity at pH 6	^Citation124
	M428L/N434S (LS)	IgG			^Citation125
	N434A	IgG			^Citation94

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