Abstract
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.
Highlights
Since the use of vaccination to eradicate smallpox, vaccines have emerged as a powerful tool for prevention and control of existing and emerging pathogens
This work serves as a pilot study to demonstrate the ability of our vaccine strategy to induce effective humoral and cellular immune responses in the BALB/c model with different adjuvant–antigen pairings
We observed robust humoral immune responses for all adjuvants paired with HA clamp and for alhydrogel, Addavax with QS21 (AdQS21), and ALF55 groups paired with respiratory syncytial virus (RSV) F clamp
Summary
Since the use of vaccination to eradicate smallpox, vaccines have emerged as a powerful tool for prevention and control of existing and emerging pathogens. Numerous vaccines have rapidly emerged amidst the COVID-19 pandemic for clinical validation, allowing the comparison of inactivated, recombinant viral, mRNA, and subunit vaccine platforms for safety and immunogenicity in completed Phase I trials that have been published following peer review [1]. From this analysis, subunit vaccines exhibited the most favorable safety and immunogenicity profile [1]. AS01, a combination of liposomes, MPLA, and saponin QS21, induces robust Th1 immune responses, enhances antigen presentation to APCs, and induces a high antibody titre [17,18,19]
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