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Vaccine
. 2026 Jan 8:74:128189.
doi: 10.1016/j.vaccine.2025.128189. Online ahead of print. A novel calcium influx inducer and a TLR7 agonist are synergistic co-adjuvants that enhance cross-reactive immunity against influenza in young and aged mice
Yumi Yokoyama 1 , Shiyin Yao 1 , Renna Cozza 1 , Fernando Gil 1 , Ian Mclaughlin 1 , Paola Anguiano Quiroz 1 , Tyler Brown 1 , Nikunj M Shukla 1 , Michael Chan 1 , Karen Messer 2 , Minya Pu 2 , Maripat Corr 1 , Dennis A Carson 3 , Tomoko Hayashi 4
Affiliations
Vaccine adjuvants play a crucial role in the efficacy of vaccines, particularly in immunocompromised populations. Newer agents and combination strategies are needed for adequate defense against emerging pathogens and their evolving variants. Here we report the benefit of a synergistic combination of two adjuvants: a Toll-like receptor 7 agonist, 1V270, and a calcium influx inducer, 2G272, that elicit Th1 and Th2 biased immune responses, respectively. In vitro,2G272 significantly enhanced cytokine production induced by 1V270 in human and mouse primary cells, compared to a low activity analog, 2E281, identified from structure-activity relationship studies. Using A/California/07/2009 (H1N1) inactivated influenza A virus (IIAV) as the antigen, the combination adjuvant (2G272 + 1V270) magnified IgG1 and IgG2a responses against hemagglutinin (HA) accompanied by greater hemagglutinin inhibition titers and increased germinal center formation in the draining lymph nodes of immunized BALB/c mice at comparable levels to FDA-approved comparators, MF59 and AS01B. The combination adjuvant also enhanced H1 HA-specific T cell responses, augmenting antigen-specific IFNγ secretion. Importantly, the 2G272 + 1V270 combined adjuvant promoted cross-reactive antibody and cellular immune responses against other HAs in phylogenic Group 1: H5, H11, and in Group 2: H3. C57BL/6 aged mice immunized with H1N1 IIAV and 2G272 + 1V270 generated significant anti-H1 IgG1 responses and IFNγ splenic T cell responses to H1 which were cross-reactive with H5 and H3. Collectively, our findings suggest that 2G272 + 1V270 may be a versatile vaccine co-adjuvant system for promoting a larger breadth of cross reactive Th1/Th2 immune responses and robust GC B cell formation, including in the elderly population.
. 2026 Jan 8:74:128189.
doi: 10.1016/j.vaccine.2025.128189. Online ahead of print. A novel calcium influx inducer and a TLR7 agonist are synergistic co-adjuvants that enhance cross-reactive immunity against influenza in young and aged mice
Yumi Yokoyama 1 , Shiyin Yao 1 , Renna Cozza 1 , Fernando Gil 1 , Ian Mclaughlin 1 , Paola Anguiano Quiroz 1 , Tyler Brown 1 , Nikunj M Shukla 1 , Michael Chan 1 , Karen Messer 2 , Minya Pu 2 , Maripat Corr 1 , Dennis A Carson 3 , Tomoko Hayashi 4
Affiliations
- PMID: 41512501
- DOI: 10.1016/j.vaccine.2025.128189
Vaccine adjuvants play a crucial role in the efficacy of vaccines, particularly in immunocompromised populations. Newer agents and combination strategies are needed for adequate defense against emerging pathogens and their evolving variants. Here we report the benefit of a synergistic combination of two adjuvants: a Toll-like receptor 7 agonist, 1V270, and a calcium influx inducer, 2G272, that elicit Th1 and Th2 biased immune responses, respectively. In vitro,2G272 significantly enhanced cytokine production induced by 1V270 in human and mouse primary cells, compared to a low activity analog, 2E281, identified from structure-activity relationship studies. Using A/California/07/2009 (H1N1) inactivated influenza A virus (IIAV) as the antigen, the combination adjuvant (2G272 + 1V270) magnified IgG1 and IgG2a responses against hemagglutinin (HA) accompanied by greater hemagglutinin inhibition titers and increased germinal center formation in the draining lymph nodes of immunized BALB/c mice at comparable levels to FDA-approved comparators, MF59 and AS01B. The combination adjuvant also enhanced H1 HA-specific T cell responses, augmenting antigen-specific IFNγ secretion. Importantly, the 2G272 + 1V270 combined adjuvant promoted cross-reactive antibody and cellular immune responses against other HAs in phylogenic Group 1: H5, H11, and in Group 2: H3. C57BL/6 aged mice immunized with H1N1 IIAV and 2G272 + 1V270 generated significant anti-H1 IgG1 responses and IFNγ splenic T cell responses to H1 which were cross-reactive with H5 and H3. Collectively, our findings suggest that 2G272 + 1V270 may be a versatile vaccine co-adjuvant system for promoting a larger breadth of cross reactive Th1/Th2 immune responses and robust GC B cell formation, including in the elderly population.