Improving Chicken Responses to Glycoconjugate Vaccination Against Campylobacter jejuni

Abstract

Campylobacter jejuni is a common cause of diarrheal disease worldwide. Human infection typically occurs through the ingestion of contaminated poultry products. We previously demonstrated that an attenuated Escherichia coli live vaccine strain expressing the C. jejuni N-glycan on its surface reduced the Campylobacter load in more than 50% of vaccinated leghorn and broiler birds to undetectable levels (responder birds), whereas the remainder of the animals was still colonized (non-responders). To understand the underlying mechanism, we conducted three vaccination and challenge studies using 135 broiler birds and found a similar responder/non-responder effect. Subsequent genome-wide association studies (GWAS), analyses of bird sex and levels of vaccine-induced IgY responses did not correlate with the responder versus non-responder phenotype. In contrast, antibodies isolated from responder birds displayed a higher Campylobacter-opsonophagocytic activity when compared to antisera from non-responder birds. No differences in the N-glycome of the sera could be detected, although minor changes in IgY glycosylation warrant further investigation. As reported before, the composition of the microbiota, particularly levels of OTU classified as Clostridium spp., Ruminococcaceae and Lachnospiraceae are associated with the response. Transplantation of the cecal microbiota of responder birds into new birds in combination with vaccination resulted in further increases in vaccine-induced antigen-specific IgY responses when compared to birds that did not receive microbiota transplants. Our work suggests that the IgY effector function and microbiota contribute to the efficacy of the E. coli live vaccine, information that could form the basis for the development of improved vaccines targeted at the elimination of C. jejuni from poultry.

Antimicrobial effect of a drinking water additive comprising four organic acids on Campylobacter load in broilers and monitoring of bacterial susceptibility

“…If we assume that in our experiment only low or very low concentrations of the supplemented acids reach the cecum, the indirect effects on Campylobacter load might be an interesting factor. While we did not include any analysis on the immune status of the chickens, in other studies, organic acids induced the formation of immunoglobulin Y ( IgY ) ( Park et al 2009 ), which was reported to induce inhibition of Campylobacter colonization ( Vandeputte et al 2019 ; Nothaft et al 2021 ).…”

Immune Impairment Associated with Vitamin A Deficiency: Insights from Clinical Studies and Animal Model Research

“… [ 219 ] Chicken Campylobacter jejuni /Vaccine Abundance of Clostridium spp., Ruminococcaceae and Lachnospiraceae was positively associated with vaccine-induced antigen-specific IgY responses. [ 220 ] …”

“…Similarly, in Pakistani children, an abundance of Gram-negative bacteria such as Serratia and E. coli correlated positively with immune responses to HRV vaccine [ 233 ]. Other microbe abundances reported to be positively correlated with vaccine immunogenicity include Bifidobacterium longum vs. polio, Bacillus Calmette-Guérin and tetanus vaccines [ 215 ], Clostridiales vs. Salmonella Typhi /cholera vaccine [ 216 , 234 ] in humans; Collinsella / Lactobacillus LGG/ Bifidobacterium Bb12 vs. RV vaccine [ 61 , 235 , 236 ], Prevotella vs. influenza A vaccine [ 219 ] in pigs; Clostridium spp., Ruminococcaceae , Lachnospiraceae vs. Campylobacter jejuni [ 220 ] in chickens. Therefore, it is well established that perturbations of the gut microbiome by either antibiotics or dietary (VAD) can have major impacts on vaccine immunogenicity.…”

Bacterial glycosylation, it’s complicated

“…Other key discoveries during this time were the observations that the C. jejuni oligosaccharyltransferase, PglB, attached sugars to a defined sequon (D/E-X 1 -N-X 2 -S/T where X 1 /X 2 cannot be proline) and that PglB would transfer any oligosaccharide (even derived from an unrelated LPS or CPS pathway) provided that the sugars were assembled on the same lipid used by the C. jejuni pathway i.e., undecaprenylphosphate (Und-P, also known as bactoprenyl) and the reducing-end sugar was an N-acetylhexosamine (Feldman et al, 2005;Kowarik et al, 2006). Due to the commonality of this N-glycan structure among all C. jejuni strains and the requirement for N-glycan expression for C. jejuni survival in chickens, we have been exploiting this heptasaccharide in the development of glycoconjugate poultry vaccines for the prevention of human foodborne illness (Nothaft et al, 2016;Nothaft et al, 2017;Nothaft et al, 2021b). For more reading on N-linked protein glycosylation in bacteria or bacterial glycoprotein biosynthesis, see (Nothaft and Szymanski, 2019) and (Nothaft and Szymanski, 2022), respectively.…”