Inactivated and subunit vaccines to prevent shigellosis

Abstract

Shigellosis remains a formidable disease globally, with children of the developing world bearing the greatest number of infections. The need for an affordable, safe and efficacious vaccine has persisted for decades. Vaccines to prevent shigellosis can be divided into living and nonliving approaches. Several nonliving Shigella vaccines are currently at different stages of development and show substantial promise. Outlined here is an overview of multiple nonliving vaccine technologies, highlighting their current status and recent advances in testing. In addition, gaps in the knowledge base regarding immune mechanisms of protection are explored.

Towards a non-living vaccine against Shigella flexneri: From the inactivation procedure to protection studies

“…Current vaccines strategies against Shigella can be grouped into two fundamental approaches: live-attenuated vaccines and nonliving vaccines [6][7][8]. While the essential concern regarding live attenuated candidates is to find the appropriate balance between immunogenicity and acceptable side effects, different scenery appears for inactivated whole cell or subunit vaccines.…”

“…Accordingly, current subcellular strategies include these antigens in their composition. For instance, LPS, IpaB and IpaC are contained in the "Invaplex 50", a subcellular vaccine candidate against shigellosis that is already under phase II of clinical trials [8]. Other approaches include IpaB and IpaD obtained by molecular recombinant techniques [50].…”

“…In the absence of an existing effective vaccine and the ever-increasing frequency of antimicrobial-resistant Shigella strains worldwide, Shigellosis has become a major source of concern [5]. Several candidate shigellosis vaccines are currently in development including live attenuated, inactivated whole cell, or subunit vaccines [6][7][8]. Considering intrinsic risk of living vaccines, the non-living vaccine alternative, including either inactivated whole-cell or acellular approaches, results the safest direction.…”

Safety and immunogenicity of an intranasal Shigella flexneri 2a Invaplex 50 vaccine

“…Several vaccine approaches to prevent shigellosis are under active investigation including live-attenuated vaccines, inactivated whole cell vaccines, subcellular vaccines and purified subunit vaccines such as O-specific polysaccharide conjugate vaccines [8,9]. The lack of a clear correlate of protection for Shigella vaccines has hampered vaccine development over the past several decades [8,10,11].…”

“…The lack of a clear correlate of protection for Shigella vaccines has hampered vaccine development over the past several decades [8,10,11]. Even so, the importance of the serotype specific LPS antigen is widely recognized and included as a component of all vaccine approaches actively being pursued.…”