Special Immunisation Groups Edwin Reynolds (Karin Batty) Disclosures- Nil

Immunology Today

• Expanded definitions for special immunisation groups • The changing face of certain special immunisation groups • Re visit the Concept of “Self” verses “Non self” verses “Altered self” • Concept of Autoimmunity verses Cancer • The new immunotherapies • Examples – Immune checkpoint inhibitors Definitions (Chapter 4 Immunisation Handbook)

• Immunocompetent – a broad term referring to normal immune system function. • Immunocompromise – a broad term referring to altered immune system function. The individual’s ability to mount an immune response may be reduced or increased because of a disease, treatment or genetic disorder. • Immunomodulation – changes in immune system function in response to medication, cancer chemotherapy or immunotherapy treatments. • Immunostimulant – a substance able to stimulate or increase an immune response. • Immunosuppression – a reduced ability to mount an immune response caused by medication, cancer chemotherapy or immunotherapy treatment. • Immunodeficiency – a reduced ability to mount an immune response and fight off infection. Immunodeﬁciency conditions are classified as primary and secondary, dependent on the cause. Adult special immunisation groups –IMAC website

• Pre or post splenectomy or functional asplenia • HIV infection • Post haematopoietic stem cell transplantation (HSCT) • Pre or post solid organ transplantation (excluding kidney) • End stage kidney disease, on dialysis or pre or post kidney transplant • Post chemotherapy • Immune mediated inflammatory diseases (Autoimmune disease) • Rapid change The Confusion

• Not just autoimmune conditions (IMID) anymore • Chemotherapy verses immunotherapy • Disease modifying agents (DMARDS) – Biologic agents • Funding issues - “Prior to planned immunosuppression for 28 days” Not following • Not just live vaccines an issue eg precaution with flu vaccine and the immune check point inhibitors • Immunotherapies • Immunosuppressive • Immunomodulatory • Immunostimulant New tables - guidelines for live vaccine administration Where possible vaccinate with live vaccines prior to advancing immunosuppression

Also refer to IMAC Factsheet: Diseases and medications when live vaccines may be contraindicated The Immune response has 2 components

• Innate immune response (Robotic response) • Phagocytosis • Complement cascade • Natural killer cell activation • Cytokines signalling -Chemotaxis • Adaptive immune response (Learnt response) • B cell maturation to produce antibody (subunit vaccines) • T cell regulation • Cytotoxic T cell activation (live vaccines) The immune response The concept of Immunological “Self”

• Self antigens • Non self antigens • Altered self antigens

• Got to avoid responding to self antigens – Autoimmunity • Non self antigens are the viruses, bacterial, parasites (pathogens) and vaccines • The adaptive immune response can learn to respond by recognising altered self antigens

Example: Immune check point inhibitors

• Immunostimulant therapy • The >4 medications • Nivolumab (Opdivo) • Pembrolizumab (Keytruda) target PD-1 protein, • Atezolizumab (Tecentriq) targets PD-L1 protein, • Ipilimumab (Yervoy) targets CTLA-4 protein • The target proteins help to distinguish self from non self New tables - guidelines for live vaccine administration Where possible vaccinate with live vaccines prior to advancing immunosuppression

Also refer to IMAC Factsheet: Diseases and medications when live vaccines may be contraindicated

The exquisite balance

• Autoimmunity vs Cancer evasion • Over stimulation – autoimmunity • Under stimulation - tumour progression • These medications remove some of that balance • By removing a normal handbrake on the immune response

Conclusion

• Initial studies show relative safety – vaccinating people on ICI • Studies are small with low power and conflicting results • No international consensus on use of vaccines while on the ICI • Lets just keep the “precaution” in place a little longer