Adjuvant Selection for Influenza and RSV Prefusion Subunit Vaccines
Ariel Isaacs,
Zheyi Li,
Stacey T. M. Cheung,
Danushka K. Wijesundara,
Christopher L. D. McMillan,
Naphak Modhiran,
Paul R. Young,
Charani Ranasinghe,
Daniel Watterson,
Keith J. Chappell
Affiliations
Ariel Isaacs
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Zheyi Li
Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
Stacey T. M. Cheung
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Danushka K. Wijesundara
The Australian Institute for Biotechnology and Nanotechnology, The University of Queensland, St Lucia, QLD 4072, Australia
Christopher L. D. McMillan
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Naphak Modhiran
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Paul R. Young
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Charani Ranasinghe
Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
Daniel Watterson
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Keith J. Chappell
School of Chemistry and Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072, Australia
Subunit vaccines exhibit favorable safety and immunogenicity profiles and can be designed to mimic native antigen structures. However, pairing with an appropriate adjuvant is imperative in order to elicit effective humoral and cellular immune responses. In this study, we aimed to determine an optimal adjuvant pairing with the prefusion form of influenza haemagglutinin (HA) or respiratory syncytial virus (RSV) fusion (F) subunit vaccines in BALB/c mice in order to inform future subunit vaccine adjuvant selection. We tested a panel of adjuvants, including aluminum hydroxide (alhydrogel), QS21, Addavax, Addavax with QS21 (AdQS21), and Army Liposome Formulation 55 with monophosphoryl lipid A and QS21 (ALF55). We found that all adjuvants elicited robust humoral responses in comparison to placebo, with the induction of potent neutralizing antibodies observed in all adjuvanted groups against influenza and in AdQS21, alhydrogel, and ALF55 against RSV. Upon HA vaccination, we observed that none of the adjuvants were able to significantly increase the frequency of CD4+ and CD8+ IFN-γ+ cells when compared to unadjuvanted antigen. The varying responses to antigens with each adjuvant highlights that those adjuvants most suited for pairing purposes can vary depending on the antigen used and/or the desired immune response. We therefore suggest that an adjuvant trial for different subunit vaccines in development would likely be necessary in preclinical studies.
