Oral Presentation Australian Society for Microbiology Annual Scientific Meeting 2019

Viral infections in the ageing: a major cause of morbidity and a challenge for vaccine development (#277)

Anthony Cunningham 1 2 , Naomi Truong 1 2 , Kerrie Sandgren 1 2 , Kirstie Bertram 1 2 , Jacinta Smith 1 2 , Jason Herbert 1 2 , Andrew Harman 1 2 , Myron Levin 3 , Thoms Heineman 4
  1. The Westmead Institute for Medical Research, Westmead, NSW, Australia
  2. University of Sydney, Sydney, Australia
  3. University of Colorado, Colorado
  4. Halozyme, San Diego

Ageing results in increased susceptibility to several bacterial and viral pathogens, eg Influenza, Respiratory Syncytial Virus (RSV), Cytomegalovirus (CMV) and Herpes zoster, owing to Immuno-senescence. This is an ageing related decline in all immune response modalities leading to increased incidence and severity of these infections. Vaccine responses to these important viral diseases are also impaired. Although immunization is one of the most effective measures for disease control, until recently we lacked vaccines for influenza and Herpes zoster with the same efficacy in this age group as paediatric vaccines (>90%) and indeed any for RSV and CMV. However there have been recent major advances in vaccine development include identification, design and production of antigens, adjuvants and mode of delivery. The new recombinant Herpes zoster vaccine is an excellent example. The combination of the most appropriate and immunodominant recombinant varicella zoster virus antigen, glycoprotein, E combined with the adjuvant system AS01B, consisting of MPL (from bacterial cell wall) and QS21 (from tree bark), resulted in 90% efficacy, even in those over 80 years. This remarkable efficacy is highly adjuvant dependent. In mice the adjuvant stimulates a cascade of innate immune responses in lymph nodes draining the intramuscular injection sites. This is followed by stimulation of CD4 and (weak) CD8 T cell immunity as well as boosting anti-gE antibody. Currently we are examining such adjuvant induced responses in human lymph node explants to compare with mouse models and how HSV naturally induces immunity after initial infection of genital mucosa. Such knowledge may help further improve vaccines by more appropriate adjuvant selection for other viral diseases in the ageing and for the closely related Herpes simplex virus (HSV).