Respiratory Syncytial Virus F Subunit Vaccine With AS02 Adjuvant Elicits Balanced, Robust Humoral and Cellular Immunity in BALB/c Mice

Abstract

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory illness, particularly in infants, the elderly, and immunocompromised adults. There is no licensed commercial vaccine against RSV. Importantly, formalin-inactivated RSV vaccines mediate enhanced respiratory disease. RSV fusion (F) protein with pre-fusion conformation is a promising candidate subunit vaccine. However, some problems remain to be solved, such as low immunogenicity and humoral immunity bias. Adjuvants can effectively enhance and adjust vaccine immune responses. In this study, we formulated pre-fusion RSV-F protein with the adjuvants, Alhydrogel, MF59, AS03, AS02, and glycol chitosan (GCS). We then conducted head-to-head comparisons of vaccine-induced immune responses in BALB/c mice. All adjuvanted vaccines enhanced antigen-specific and neutralizing antibody titers and viral clearance and gave an order of adjuvant activity: AS02 > AS03, MF59 > GCS, and Alhydrogel. Among them, AS02 elicited the highest antibody expression, which persisted until week 18. Moreover, AS02 significantly enhanced Th1 type immune response in immunized mice. Mice in the AS02 group also showed faster recovery from viral attacks in challenge tests. Further transcriptome analysis revealed that AS02 regulates immune balance by activating TLR-4 and promotes Th1-type immune responses. These results suggest that AS02 may be an excellent candidate adjuvant for RSV-F subunit vaccines. This study also provides valuable information regarding the effect of other adjuvants on immune responses of RSV-F subunit vaccines.

Protective antibodies elicited by SARS-CoV-2 spike protein vaccination are boosted in the lung after challenge in nonhuman primates

“…By comparing the immune response to preS dTM formulations with and without AS03, it is clear that AS03 is critical for the induction of protective antibody responses, as has been previously observed with influenza ( 36 , 37 , 51 , 52 ) and respiratory syncytial virus (RSV) ( 53 ). The CD4 T cell responses to spike were primarily T H 0, given the relative limited IFN-γ production ( 46 ), and T H 2.…”

“…These studies provide new insights into protective antibody responses, most notably in the lung, which are critical for understanding how vaccines limit disease, a primary end point in all clinical trials. By comparing the immune response to preS dTM formulations with and without AS03, it is clear that AS03 is critical for the induction of protective antibody responses, as has been previously observed with influenza (36,37,51,52) and respiratory syncytial virus (RSV) (53). The CD4 T cell responses to spike were primarily T H 0, given the relative limited IFN- production (46), and T H 2.…”

Vaccination with SARS-CoV-2 Spike Protein and AS03 Adjuvant Induces Rapid Anamnestic Antibodies in the Lung and Protects Against Virus Challenge in Nonhuman Primates

“…By comparing the immune response to preS dTM formulations with and without AS03, it is clear that AS03 is critical for the induction of protective antibody responses, as has been previously observed with influenza 35, 36, 51, 52 and respiratory syncytial virus (RSV) 53 . The CD4 responses to spike were primarily T H 0 given the relative limited IFNγ production 46 and T H 2.…”

HRSV prefusion-F protein with Adju-Phos adjuvant induces long-lasting Th2-biased immunity in mice

“…Therefore, it is necessary to conduct adjuvant tests on subunit vaccines in preclinical studies. The ideal adjuvants for hRSV screened by previous researchers were all antigens expressed with mammalian cells [ 42 ]. The interaction between proteins expressed by different expression systems and adjuvants is different.…”