A reference, inactivated, epidemic typhus vaccine: laboratory evaluation of candidate vaccines

Mason, Richard; Seligmann, Edward B.; Ginn, Robert K.

doi:10.1016/s0092-1157(76)80005-4

Cited by 4 publications

(1 citation statement)

References 10 publications

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“…The potency tests required by the Food and Drug Administration for release of production lots of these vaccines assayed antibodies to R. rickettsii or R. prowazekii by a particular cumbersome method, the titer of neutralization by the sera of immunized guinea pigs of rickettsial “toxicity” to mice [16]. This approach utilized a curious animal model that does not represent rickettsial infection, the death of mice inoculated intravenously with an extremely high dose of rickettsiae in less than 24 h. However, contemporary knowledge reveals that the rickettsial antigens that were critical to neutralizing this effect are conformational epitopes of outer membrane proteins (Omp) A and B for R. rickettsii and OmpB for R. prowazekii [17].…”

Section: Introductionmentioning

confidence: 99%

The realities of biodefense vaccines against Rickettsia

Walker

2009

Vaccine

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Rickettsia prowazekii, R. rickettsii, R. conorii, and R. typhi are serious biologic weapon threats because of high infectivity of low dose aerosols, stable small particle aerosol infectivity, virulence causing severe disease, difficulty in establishing a timely diagnosis, ineffectiveness of usual empiric treatments, potential for engineered complete antimicrobial resistance, lower level of immunity, availability of the agents in nature, and feasibility of propagation, stabilization, and dispersal.Infection induces long-term immunity, killed rickettsial vaccines stimulate incomplete protection, and a live attenuated mutant stimulates strong immunity but reverts to virulence, Prospects for rational development of a safe, effective live attenuated vaccine are excellent.

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Section: Introductionmentioning

confidence: 99%

The realities of biodefense vaccines against Rickettsia

Walker

2009

Vaccine

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Phenotype of the anti-Rickettsia CD8+ T cell response suggests cellular correlates of protection for the assessment of novel antigens

Caro-Gómez

Gaži

Cespedes

et al. 2014

Vaccine

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The obligately intracellular bacteria Rickettsia infect endothelial cells and cause systemic febrile diseases that are potentially lethal. No vaccines are currently available and current knowledge of the effective immune response is limited. Natural and experimental rickettsial infections provide strong and cross-protective cellular immunity if the infected individual survives the acute infection. Although resistance to rickettsial infections is attributed to the induction of antigen-specific T cells, particularly CD8+ T cells, the identification and validation of correlates of protective cellular immunity against rickettsial infections, an important step towards vaccine validation, remains a gap in this field. Here, we show that after a primary challenge with Rickettsia typhi in the C3H mouse model, the peak of anti-Rickettsia CD8+ T cell-mediated responses occurs 7 days post-infection (dpi), which coincides with the beginning of rickettsial clearance. At this time point, both effector-type and memory-type CD8+ T cells are present, suggesting that 7 dpi is a valid time point for the assessment of CD8+ T cell responses of mice previously immunized with protective antigens. Based on our results, we suggest four correlates of cellular protection for the assessment of protective rickettsial antigens: 1) production of IFN-γ by antigen experienced CD3+CD8+CD44high cells, 2) production of Granzyme B by CD27lowCD43low antigen-experienced CD8+ T cells, 3) generation of memory-type CD8+ T cells [Memory Precursor Effector Cells (MPECs), as well as CD127highCD43low, and CD27highCD43low CD8+ T cells], and 4) generation of effector-like memory CD8+ T cells (CD27lowCD43low). We propose that these correlates could be useful for the general assessment of the quality of the CD8+ T cell immune response induced by novel antigens with potential use in a vaccine against Rickettsia.

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