Syntheses of Salmonella Paratyphi A Associated Oligosaccharide Antigens and Development towards Anti‐Paratyphoid Fever Vaccines

Abstract

With the emergence of multidrug resistant Salmonella strains, the development of anti-Salmonella vaccines is an important task. Currently there are no approved vaccines against Salmonella Paratyphi A, the leading cause of paratyphoid fever.T of ill this gap, oligosaccharides corresponding to the O-polysaccharider epeating units from the surface of Salmonella Paratyphi Ah ave been synthesizedt hrough convergents tereoselective glycosylations.T he synthetic glycan antigenwas conjugatedw ith ap owerful immunogenic carrier system, the bacteriophage Qb.T he resulting construct was able to elicit stronga nd long-lasting anti-glycan IgG an-tibodyr esponses, which wereh ighly selectivetoward Salmonella Paratyphi Aa ssociated glycans. The availability of welldefined glycana ntigen enabledt he determinationt hat one repeating unit of the polysaccharide is sufficient to induce protectivea ntibodies, and the paratose residue and/ort he O-acetyl modificationso nt he backbonea re important for recognition by antibodies elicited by aQ b-tetrasaccharide conjugate. Immune sera provided excellentp rotection to mice from lethal challenge with Salmonella Paratyphi A, highlighting the potentialo ft he synthetic glycan-based vaccine.

Generalized Modules for Membrane Antigens as Carrier for Polysaccharides: Impact of Sugar Length, Density, and Attachment Site on the Immune Response Elicited in Animal Models

“…Also additional nanoparticle systems, such as Qβ ( 56 , 57 ) and hepatitis B core antigen virus-like particles ( 58 ), are being proposed as novel carrier systems to provide a strong anti-PS immune response. It will be interesting to compare GMMA and OMVs with these other systems for their ability to induce strong response after one only injection, persistency of the response, memory, and ultimately efficacy in infants and to see if they will behave similarly mainly due to their particulate nature and display of multiple antigens or if there will be specific features for a difference.…”

Paratyphoid Fever A: Infection and Prevention

“…Synthesis of oligosaccharide antigens can avoid the detoxification procedure. Dhara et al (2020) used synthetic oligosaccharides corresponding to the O-polysaccharide repeating units of S. Paratyphi A to generate glycocojugate by binding to a carrier, bacteriophage Qβ. The conjugate elicited high level of anti-glycan IgG antibodies in mice.…”

“…The conjugate elicited high level of anti-glycan IgG antibodies in mice. Passive immunization with the antisera protected mice from the lethal challenges with S. Paratyphi A (Dhara et al, 2020).…”

Semi- and fully synthetic carbohydrate vaccines against pathogenic bacteria: recent developments

“…The tetrasaccharide — Qβ conjugates elicited a potent IgG antibody response in mice and rabbits ( Figure 10 ) [ 78 ]. Later, the same concept of a vaccine candidate was tested with synthetic oligosaccharides from Salmonella enterica serovar Paratyphi A exhibiting potent IgG antibody responses in animals [ 79 ].…”