Table 2 Licensed monovalent glycoconjugate vaccines against Hib^a.

Name	Current producer	Scientific compound nomenclature	First licensure	Glycan sizing	Glycan size	Glycan activation	Linker	Protein activation	Conjugation	Protein carrier
End-linked conjugation
HibTITER^b	Nuron Biotech^c	PRP-CRM₁₉₇, HbOC	1988	Periodate oxidation^d	OS^e	Periodate oxidation^d	n.a.	n.a.	Peductive amination	CRM₁₉₇
Vaxem-Hib^f	GSK	PRP-CRM₁₉₇	1995	Acid hydrolysis	OS	Amine^g	NHS diester	n.a.	Amidation	CRM₁₉₇
Quimi-Hib	Center for Genetic Engineering & Biotechnology	PRP-T, PRP-TT, sHbOT	2004	n.a.	OS^h	Maleimide	3-Maleimidopropionateⁱ	Thiol	Thioether	TT
Cross-linked conjugation
ProHIBiT^j	Sanofi	PRP-D, PRP-DT	1987	Heat	PS^k	CNBr^l	ADH	Active ester^m	Amidation	DT
PedvaxHIB	Merck & Co.	PRP-OMP, PRP-OMPC	1989	n.a.	PS^k	Bromide	Bigeneric spacer	Thiol	Thioether	OMPC
OmniHIBⁿ	GSK	PRP-T, PRP-TT	1993	Alkaline hydrolysis^o	PS^p	CNBr^l	ADH	Active ester^m	Amidation	TT
ActHIB	Sanofi
BioHib	Bharat Biotech
novoHib	Panacea Biotec
Hiberix	GSK
SII HibPRO	Serum Institute of India	PRP-T, PRP-TT	2007	Alkaline hydrolysis^q	PS^q	CNBr^l	ADH	Active ester^m	Amidation	TT
HiBE	Biological E., Ltd.	PRP-T, PRP-TT	2007	Alkaline hydrolysis^q	PS^q	CNBr^l	ADH	Active ester^m	Amidation	TT

Hib H. influenzae type b, n.a. not available.
^aExcludes combination vaccines.
^bVaccine was discontinued in 2007, originally developed by Pfizer.
^cCurrently in reorganization proceedings.
^dSimultaneous depolymerization and activation, which cleaves between two contiguous hydroxyl groups (on the ribitol moiety) and activates both ends. The resulting conjugate is primarily end-linked, but can also contain cross-linked molecules, albeit to a much lesser extent than conjugates made from randomly activated PS.
^eApproximately 20 RU.
^fVaccine discontinued in 2017, originally developed by Novartis.
^gReductive amination with diamino linker, activating reducing end of the OSs.
^hApproximately 8 RU.
ⁱSynthetic OS contains a built-in amino linker, extended by activation with N-hydroxysuccinimidyl 3-maleimidopropionate.
^jVaccine discontinued in 2000.
^kMedium size, according to ref. ⁸⁸.
^lRandom activation of hydroxyl groups.
^mForms in situ by N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide (EDC) during conjugation.
ⁿVaccine discontinued, originally developed by Pasteur Mérieux Vaccins, replaced by Hiberix.
^oPartial depolymerization during activation in an alkaline buffer.
^pLarge size, according to ref. ⁸⁸.
^qControlled depolymerization to ~200 kDa¹²⁶ during activation in an alkaline buffer.

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