GETTING TO THE GUTS OF IT: EVALUATING FACTORS THAT INFLUENCE VACCINE HYPO-RESPONSIVENESS IN PATIENTS RECEIVING MAINTENANCE HAEMODIALYSIS

Dr Erin Vaughan1, Dr ALEXANDER GILBERT1, Dr GRIFFITH PERKINS2, Prof STEVE CHADBAN1

1Royal Price Alfred Hospital, Camperdown 2050, Australia, 2The University of Adelaide, Adelaide 5000, Australia

Biography:

Dr Erin Vaughan (B.BioMed, MBBS, FRACP, M. Clin Epi) is a Staff Specialist Nephrologist at RPA Hospital with clinical interest and expertise in obstetric nephrology, dialysis and kidney supportive care. She is Co-Director of ANZSN Kidney School Program and member of ANZDATA Parenthood Working Group and ANZSPAM Kidney Supportive Care Special Interest Group. Dr Vaughan combines her academic interests with clinical training and mentorship roles for both basic and advanced trainees. She is passionate about improving consumer experiences and fostering a culture of wellbeing in medicine and medical training.

Background:

Dialysis patients experience a high burden of vaccine-preventable diseases and vaccine hypo-responsiveness is a key contributor. Uraemic toxins and gut dysbiosis are potential mechanisms of immune dysfunction in people with kidney failure.

Aim:

To determine whether gut microbiota composition and uraemic toxin concentrations associate with vaccine response.

Methods:

A cross-sectional descriptive study of 51 haemodialysis patients was conducted. Demographic, vaccination, and serological data were collected. Associations between uraemic toxin concentrations (indoxyl sulphate [IS], p-cresyl sulphate [PCS], and trimethylamine N-oxide [TMAO]), microbiota composition (by 16S rRNA gene sequencing) and vaccine responsiveness (RBD-Ig and nucleocapsid-specific anti-SARS-CoV-2 antibodies) were evaluated.

Results:

Fifty-one participants (43% female, mean age 66) were included; 59% were Caucasian. Diabetes (37%) was the leading cause of kidney failure. Following a two-dose schedule with Pfizer (69%) or AstraZeneca (29%) COVID-19 vaccines, 71% and 70% of recipients were responders, respectively. Of those who received Hepatitis B vaccination, 50% responded, with a significant association between COVID-19 and hepatitis B vaccine responses (χ² = 4.39, p = 0.036). No significant association was evident between serum uraemic toxin (PCS , IS or TMAO) concentrations (all p>0.2) and COVID-19 vaccine responses. Total toxin burden was numerically but not significantly greater in non-responders (p = 0.42).

Microbiota analysis showed elevated PCS and IS concentrations were associated with increased abundance of potentially pathogenic genera (Escherichia/Shigella, Streptococcus) and decreased abundance of short chain fatty acid (SCFA)-producing taxa (Bifidobacterium bifidum, Anaerostipes, Eubacterium, Faecalimonas). A greater abundance of SCFA-producers (Odoribacter, Parabacteroides, Coprobacter) were significantly associated with vaccine responsiveness.

Conclusion:

Microbiota composition may influence vaccine responsiveness; however, relationship with uraemic toxins were minimal. Further research is needed before pursuing microbiome-targeted strategies to enhance vaccine efficacy.

 

 

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