Multivalent vaccines demonstrate immunogenicity and protect against Coxiella burnetii aerosol challenge

Abstract

Vaccines are among the most cost-effective public health measures for controlling infectious diseases. Coxiella burnetii is the etiological agent of Q fever, a disease with a wide clinical spectrum that ranges from mild symptoms, such as fever and fatigue, to more severe disease, such as pneumonia and endocarditis. The formalin-inactivated whole-cell vaccine Q-VAX® contains hundreds of antigens and confers lifelong protection in humans, but prior sensitization from infection or vaccination can result in deleterious reactogenic responses to vaccination. Consequently, there is great interest in developing non-reactogenic alternatives based on adjuvanted recombinant proteins. In this study, we aimed to develop a multivalent vaccine that conferred protection with reduced reactogenicity. We hypothesized that a multivalent vaccine consisting of multiple antigens would be more immunogenic and protective than a monovalent vaccine owing to the large number of potential protective antigens in the C. burnetii proteome. To address this, we identified immunogenic T and B cell antigens, and selected proteins were purified to evaluate with a combination adjuvant (IVAX-1), with or without C. burnetii lipopolysaccharide (LPS) in immunogenicity studies in vivo in mice and in a Hartley guinea pig intratracheal aerosol challenge model using C. burnetii strain NMI RSA 493. The data showed that multivalent vaccines are more immunogenic than monovalent vaccines and more closely emulate the protection achieved by Q-VAX. Although six antigens were the most immunogenic, we also discovered that multiplexing beyond four antigens introduces detectable reactogenicity, indicating that there is an upper limit to the number of antigens that can be safely included in a multivalent Q-fever vaccine. C. burnetii LPS also demonstrates efficacy as a vaccine antigen in conferring protection in an otherwise monovalent vaccine formulation, suggesting that its addition in multivalent vaccines, as demonstrated by a quadrivalent formulation, would improve protective responses.

Sterile protection againstP. vivaxmalaria by repeated blood stage infection in theAotusmonkey model

“…A P. vivax in vitro transcription/translation (IVTT) reaction protein microarray revealed antibody responses against major vivax core gene and is displayed according to the fold change in expression (x-axis, in log 2 ) and statistical significance (y-axis, in negative logarithm to the base 10 of the immunogenic blood stage antigens (Ags) in this study. This approach was supported by previous studies, which demonstrated the utility of the IVTT platform in high-throughput antigen discovery across several disease areas (84,85,86,87,88). Immune reactivity to individual antigens and antibody breadth in sera from these animals increased with each inoculation level and were statistically significantly different between inoculation levels I and III, when the animals achieved sterile immunity to a homologous SAL-1 challenge.…”

Design of multi‐epitope chimeric vaccine against Monkeypox virus and SARS‐CoV‐2: A vaccinomics perspective

“… 63 Similarly, Q‐VAX is a licensed formalin‐inactivated whole‐cell vaccine against Coxiella burnetii , the causative agent of Q fever. 64 These studies proved the explitation of chimeric vaccine but for different strains of the same pathogens. The present study designed chimeric vaccine against two distinctly viral pathogens, namely SARS‐CoV‐2 and MPXV.…”

Vaccine development: obligate intracellular bacteria new tools, old pathogens: the current state of vaccines against obligate intracellular bacteria

“…and O. tsutsugamuschi , however, surface exposed protein antigens are still likely candidates for these bacteria ( Luo et al., 2020 ). For example, the LPS from C. burnetii has been demonstrated to confer protection in both mice and guinea pigs ( Zhang et al., 2007 ; Jan et al., 2023 ).…”