Adjuvanting a subunit SARS-CoV-2 vaccine with clinically relevant adjuvants induces durable protection in mice

• Published in: npj vaccines 2022-05, Vol.7 (1), p.55-55, Article 55
• Main Authors: Grigoryan, Lilit, Lee, Audrey, Walls, Alexandra C., Lai, Lilin, Franco, Benjamin, Arunachalam, Prabhu S., Feng, Yupeng, Luo, Wei, Vanderheiden, Abigail, Floyd, Katharine, Wrenn, Samuel, Pettie, Deleah, Miranda, Marcos C., Kepl, Elizabeth, Ravichandran, Rashmi, Sydeman, Claire, Brunette, Natalie, Murphy, Michael, Fiala, Brooke, Carter, Lauren, Coffman, Robert L., Novack, David, Kleanthous, Harry, O’Hagan, Derek T., van der Most, Robbert, McLellan, Jason S., Suthar, Mehul, Veesler, David, King, Neil P., Pulendran, Bali
• Format: Article
• Language: English
• Subjects: 631/250; 631/250/590; Adjuvants; Animal models; Biomedical and Life Sciences; Biomedicine; Comparative studies; Immune response; Immunization; Infectious Diseases; Ligands; Medical Microbiology; Public Health; Severe acute respiratory syndrome coronavirus 2; Vaccine; Vaccines; Virology
• ISSN: 2059-0105; 2059-0105
• DOI: 10.1038/s41541-022-00472-2

Adjuvants enhance the magnitude and the durability of the immune response to vaccines. However, there is a paucity of comparative studies on the nature of the immune responses stimulated by leading adjuvant candidates. In this study, we compared five clinically relevant adjuvants in mice—alum, AS03 (a squalene-based adjuvant supplemented with α-tocopherol), AS37 (a TLR7 ligand emulsified in alum), CpG1018 (a TLR9 ligand emulsified in alum), O/W 1849101 (a squalene-based adjuvant)—for their capacity to stimulate immune responses when combined with a subunit vaccine under clinical development. We found that all four of the adjuvant candidates surpassed alum with respect to their capacity to induce enhanced and durable antigen-specific antibody responses. The TLR-agonist-based adjuvants CpG1018 (TLR9) and AS37 (TLR7) induced Th1-skewed CD4+ T cell responses, while alum, O/W, and AS03 induced a balanced Th1/Th2 response. Consistent with this, adjuvants induced distinct patterns of early innate responses. Finally, vaccines adjuvanted with AS03, AS37, and CpG1018/alum-induced durable neutralizing-antibody responses and significant protection against the B.1.351 variant 7 months following immunization. These results, together with our recent results from an identical study in non-human primates (NHPs), provide a comparative benchmarking of five clinically relevant vaccine adjuvants for their capacity to stimulate immunity to a subunit vaccine, demonstrating the capacity of adjuvanted SARS-CoV-2 subunit vaccines to provide durable protection against the B.1.351 variant. Furthermore, these results reveal differences between the widely-used C57BL/6 mouse strain and NHP animal models, highlighting the importance of species selection for future vaccine and adjuvant studies.