Abstract
Vaccination remains one of the most successful medical interventions in history, significantly decreasing morbidity and mortality associated with, or even eradicating, numerous infectious diseases. Although traditional immunization strategies have recently proven insufficient in the face of many highly mutable and emerging pathogens, modern strategies aim to rationally engineer a single antigen or cocktail of antigens to generate a focused, protective immune response. However, the effect of cocktail vaccination (simultaneous immunization with multiple immunogens) on the antibody response to each individual antigen within the combination, remains largely unstudied. To investigate whether immunization with a cocktail of diverse antigens would result in decreased antibody titer against each unique antigen in the cocktail compared to immunization with each antigen alone, we immunized mice with surface proteins from uropathogenic Escherichia coli, Mycobacterium tuberculosis, and Neisseria meningitides, and monitored the development of antigen-specific IgG antibody responses. We found that antigen-specific endpoint antibody titers were comparable across immunization groups by study conclusion (day 70). Further, we discovered that although cocktail-immunized mice initially elicited more robust antibody responses, the rate of titer development decreases significantly over time compared to single antigen-immunized mice. Investigating the basic properties that govern the development of antigen-specific antibody responses will help inform the design of future combination immunization regimens.
Highlights
The design and implementation of successful immunization regimens worldwide have cemented vaccination as one of the most important human medical interventions in history [1,2,3,4,5]
We hypothesized that immunization with a cocktail of structurally, and functionally diverse antigens would result in decreased antibody titer against each unique antigen in the cocktail, compared to mice immunized with each antigen alone
We chose the iron-regulated outer membrane protein IreA, from uropathogenic Escherichia coli, which is exclusively expressed by pathogenic strains of E. coli and facilitates nutrient metal acquisition [16,17,18]; the heparin-binding hemagglutinin protein HBHA from Mycobacterium tuberculosis, which facilities bacterial dissemination from the lung [19,20,21]; and the factor H-binding protein fHbp from Neisseria meningitides, which facilitates bacterial innate immune evasion [15,22,23]
Summary
The design and implementation of successful immunization regimens worldwide have cemented vaccination as one of the most important human medical interventions in history [1,2,3,4,5]. Traditional vaccination strategies utilizing immunization with a live-attenuated or inactivated agent have proven insufficient in the face of many contemporary epidemic, highly mutable, and emerging pathogens [6,7]. Modern strategies aim to rationally engineer a single antigen or cocktail of antigens to generate a more focused, protective immune response [8,9,10,11]. Immunization with multiple immunogens) has on the antibody response to each individual antigen within the combination remains largely unstudied. We sought to characterize the effect of cocktail vaccination on the immunogenicity of pathogen-derived protein antigens. We immunized mice with cell surface-exposed proteins from uropathogenic Escherichia coli, Mycobacterium tuberculosis, and Neisseria meningitides, and monitored the development of antigen-specific IgG antibody responses in BALB/c mice
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