1. Fig. 6 Multivalent DNA vaccine and protein antigen delivery by T4-AAV nanoparticles.
Multivalent DNA vaccine and protein antigen delivery by T4-AAV nanoparticles. (A) Formulations used for mice vaccinations. (B) Prime-boost immunization scheme. The days of prebleeding (pre.), bleeding, prime, boost, and challenge with Y. pestis are indicated. (C and D) Sera from the PBS, T4, T4(HA4900), and T4(HA4900)-AAV(VRCO1) groups were assessed for specific anti-HA IgG/G1/G2a antibody titers by ELISA on day 14 (prime) (C) and day 35 (boost) (D). (E) Measurement of anti-HA IgG2a antibody titers in sera from groups T4, T4(HA4900), and T4(HA4900)-AAV(VRCO1) at serial time points (on prebleeding day and days 14, 35, 60, 120, and 180). (F) Serum CXCL13 concentration (ng/ml) in mice immunized with T4(HA4900) or T4(HA4900)-AAV(VRCO1) at prebleeding day and days 14, 35, 60, and 180 after immunization. (G) Comparison of anti-HA antibody titers in sera from groups T4, T4(HA4900), T4(HA4900)-AAV(VRCO1), and F1mutV-T4(HA4900)-AAV(VRCO1) on day 35. (H and I) Anti-F1mutV–specific antibody (IgG/G1/G2a) titers were determined by ELISA using sera from mice vaccinated with T4(HA4900)-AAV(VRCO1) and F1mutV-T4(HA4900)-AAV(VRCO1) on days 14 (H) and 35 (I). (J) Comparison of anti-F1mutV IgG antibody titers in sera from groups T4, AAV, F1mutV-T4(HA4900), and F1mutV-T4(HA4900)-AAV on day 35. (K) Kaplan-Meier survival curves of mice against intranasal pneumonic plague challenge with 295 LD50 (median lethal dose) of Y. pestis CO92 (1 LD50 = 100 colony-forming units in BALB/c mice). (L) Anti-HA–specific antibody titers in immunized sera from the F1mutV-T4-AAV(HA4900) group at various time points. (M) Comparison of anti-F1mutV antibody titers in sera from groups T4(HA4900)-AAV, T4-AAV(HA4900), F1mutV-T4(HA4900)-AAV, and F1mutV-T4-AAV(HA4900) on day 35. The values represent means ± SD of three independent replicates. **P < 0.01 compared with the T4(HA4900) vaccination. *P < 0.05 compared with the F1mutV-T4 vaccination. Statistical significance was determined using two-tailed Student’s t tests. N.D., not detected. See Materials and Methods for additional details.
Jingen Zhu et al. Sci Adv 2019;5:eaax0064
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