STING-adjuvanted outer membrane vesicle nanoparticle vaccine against Pseudomonas aeruginosa
Elisabet Bjånes, Nishta Krishnan, Truman Koh, Anh T.P. Ngo, Jason Cole, Joshua Olson, Ingrid Cornax, Chih-Ho Chen, Natalie Chavarria, Samira Dahesh, Shawn M. Hannah, Alexandra Stream, Jiaqi Amber Zhang, Hervé Besançon, Daniel Sun, Siri Yendluri, Sydney Morrill, Jiarong Zhou, Animesh Mohapatra, Ronnie H. Fang, Victor Nizet
Elisabet Bjånes, Nishta Krishnan, Truman Koh, Anh T.P. Ngo, Jason Cole, Joshua Olson, Ingrid Cornax, Chih-Ho Chen, Natalie Chavarria, Samira Dahesh, Shawn M. Hannah, Alexandra Stream, Jiaqi Amber Zhang, Hervé Besançon, Daniel Sun, Siri Yendluri, Sydney Morrill, Jiarong Zhou, Animesh Mohapatra, Ronnie H. Fang, Victor Nizet
View: Text | PDF
Research Article Infectious disease Microbiology Vaccines

STING-adjuvanted outer membrane vesicle nanoparticle vaccine against Pseudomonas aeruginosa

Abstract

Multidrug-resistant (MDR) bacterial pneumonia poses a critical threat to global public health. The opportunistic Gram-negative pathogen Pseudomonas aeruginosa is a leading cause of nosocomial-associated pneumonia, and an effective vaccine could protect vulnerable populations, including the elderly, immunocompromised, and those with chronic respiratory diseases. Highly heterogeneous outer membrane vesicles (OMVs), shed from Gram-negative bacteria, are studded with immunogenic lipids, proteins, and virulence factors. To overcome limitations in OMV stability and consistency, we described what we believe to be a novel vaccine platform that combines immunogenic OMVs with precision nanotechnology — creating a bacterial cellular nanoparticle (CNP) vaccine candidate, termed Pa-STING CNP, which incorporates an adjuvanted core that activates the STING (stimulator of interferon genes) pathway. In this design, OMVs are coated onto the surface of self-adjuvanted STING nanocores. Pa-STING CNP vaccination induced substantial antigen presenting cell recruitment and activation in draining lymph nodes, robust anti-Pseudomonas antibody responses, and provided protection against lethal challenge with the hypervirulent clinical P. aeruginosa isolate PA14. Antibody responses mediated this protection and provided passive immunity against the heterologous P. aeruginosa strain PA01. These findings provided evidence that nanotechnology can be used to create a highly efficacious vaccine platform against high priority MDR pathogens such as P. aeruginosa.

Authors

Elisabet Bjånes, Nishta Krishnan, Truman Koh, Anh T.P. Ngo, Jason Cole, Joshua Olson, Ingrid Cornax, Chih-Ho Chen, Natalie Chavarria, Samira Dahesh, Shawn M. Hannah, Alexandra Stream, Jiaqi Amber Zhang, Hervé Besançon, Daniel Sun, Siri Yendluri, Sydney Morrill, Jiarong Zhou, Animesh Mohapatra, Ronnie H. Fang, Victor Nizet

×

Figure 4

Pa-STING vaccination induces robust IgG responses and protects against lethal pneumonia.

Options: View larger image (or click on image) Download as PowerPoint
Pa-STING vaccination induces robust IgG responses and protects against l...
(A) Active immunization scheme with RBC-STING and Pa-STING, Mice were immunized subcutaneously with 0.01, 0.1, or 1 μg Pa-STING. Controls were immunized with the highest RBC-STING dose. Mortality curves in (B) female (♀) and (C) male (♂) nonimmunized mice identifying the effective lethal dose of PA14 pneumonia. Mice were infected with 0.7–2 × 107 CFUs PA14 intratracheally and monitored for mortality for 7 days. n = 5/group, representative of 2 independent experiments. Mortality curves in (D) female (♀) and (E) male (♂) immunized mice infected with PA14. Mice were vaccinated with 0.01, 0.1, or 1 μg Pa-STING or 1 μg RBC-STING subcutaneously on days 0, 7, and 14. Mice were intratracheally infected with ~ 1 × 107 CFUs PA14 on day 28. Morbidity and mortality were monitored twice daily for 7 days. n = 5–10/group. Representative of 2 independent experiments. (F and G) Anti-Pa IgG titers from (D and E), respectively. Titers were assessed by mandibular cheek bleeding and ELISAs on days 0, 7, 14, and 28. (H) Clinical daily scores for unvaccinated mice infected with 0.7–2 × 107 CFUs PA14. Means ± SEM. n = 10/group, 2 independent experiments pooled. (I) Mortality curves in immunized mice infected with PA14. Mice were vaccinated with 1, 2, or 3 doses of 0.01 μg Pa-STING or 3 doses of 0.01 μg RBC-STING subcutaneously on days 0, 7, and 14. Mice were intratracheally infected with ~ 1 × 107 CFUs PA14 on day 28. Mortality was monitored for 5 days. n = 10–15/group. Two independent experiments pooled. (J) Anti-Pa IgG titers from I. Each dot represents a mouse. n = 5–10 per group, representative of 2 independent experiments. (K) Percentage change in weight from day 28 and (L) clinical score in mice vaccinated and infected from I. (D, E, and I) Kaplan-Meier (Log-Rank) test. (F, G, and J–L) Mixed model 2-way ANOVA with Dunnet’s multiple comparisons post test. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.