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The neglected challenge: Vaccination against rickettsiae.

ABSTRACT: Over the last decades, rickettsioses are emerging worldwide. These diseases are caused by intracellular bacteria. Although rickettsioses can be treated with antibiotics, a vaccine against rickettsiae is highly desired for several reasons. Rickettsioses are highly prevalent, especially in poor countries, and there are indications of the development of antibiotic resistance. In addition, some rickettsiae can persist and cause recurrent disease. The development of a vaccine requires the understanding of the immune mechanisms that are involved in protection as well as in immunopathology. Knowledge about these immune responses is accumulating, and efforts have been undertaken to identify antigenic components of rickettsiae that may be useful as a vaccine. This review provides an overview on current knowledge of adaptive immunity against rickettsiae, which is essential for defense, rickettsial antigens that have been identified so far, and on vaccination strategies that have been used in animal models of rickettsial infections.

SUBMITTER: Osterloh A

PROVIDER: S-EPMC7581008 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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The neglected challenge: Vaccination against rickettsiae.

Osterloh Anke A

PLoS neglected tropical diseases 20201022 10

Over the last decades, rickettsioses are emerging worldwide. These diseases are caused by intracellular bacteria. Although rickettsioses can be treated with antibiotics, a vaccine against rickettsiae is highly desired for several reasons. Rickettsioses are highly prevalent, especially in poor countries, and there are indications of the development of antibiotic resistance. In addition, some rickettsiae can persist and cause recurrent disease. The development of a vaccine requires the understandi ...[more]

PMID: 33091016

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Project description:BACKGROUND: Over the past two decades, international health policies focusing on the fight against the human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS), tuberculosis (TB), malaria, and those diseases that address maternal and child health problems, among others, have skewed disease control priorities in China and other Asian countries. Although these are important health problems, an epidemic of chronic, non-communicable diseases (NCDs) in China has accounted for a much greater burden of disease due to the ongoing rapid socioeconomic and demographic transition. DISCUSSION: Although NCDs currently account for more than 80% of the overall disease burden in China, they remain very low on the nation's disease control priorities, attracting marginal investment from central and local governments. This leaves the majority of patients with chronic conditions without effective treatment. International organizations and national governments have recognized the devastating social and economic consequences caused by NCDs in low- and middle-income countries, including China. Yet, few donor-funded projects that address NCDs have been implemented in these countries over the past decade. Due to a lack of strong support from international organizations and national governments for fighting against NCDs, affected persons in China, especially the poor and those who live in rural and less developed regions, continue to have limited access to the needed care. Costs associated with frequent health facility visits and regular treatment have become a major factor in medical impoverishment in China. This article argues that although China's ongoing health system reform would provide a unique opportunity to tackle current public health problems, it may not be sufficient to address the emerging threat of NCDs unless targeted steps are taken to assure that adequate financial and human resources are mapped for effective control and management of NCDs in the country. SUMMARY: The Chinese government needs to develop a domestically-driven and evidence-based disease control policy and funding priorities that respond appropriately to the country's current epidemiological transition, and rapid sociodemographic and lifestyle changes.

Project description:Brucellosis remains a significant zoonotic threat worldwide. Humans and animals acquire infection via their oropharynx and upper respiratory tract following oral or aerosol exposure. After mucosal infection, brucellosis develops into a systemic disease. Mucosal vaccination could offer a viable alternative to conventional injection practices to deter disease. Using a nasal vaccination approach, the ?znuA B. melitensis was found to confer potent protection against pulmonary Brucella challenge, and reduce colonization of spleens and lungs by more than 2500-fold, with >50% of vaccinated mice showing no detectable brucellae. Furthermore, 10-fold more brucellae-specific, interferon-? (IFN-?)-producing CD8(+) T cells than CD4(+) T cells were induced in the spleen and respiratory lymph nodes. Evaluation of pulmonary and splenic CD8(+) T cells from mice vaccinated with ?znuA B. melitensis revealed that these expressed an activated effector memory (CD44(hi)CD62L(lo)CCR7(lo)) T cells producing elevated levels of IFN-?, tumor necrosis factor-?, perforin and granzyme B. To assess the relative importance of these increased numbers of CD8(+) T cells, CD8(-/-) mice were challenged with virulent B. melitensis, and they showed markedly increased bacterial loads in organs in contrast to similarly challenged CD4(-/-) mice. Only ?znuA B. melitensis- and Rev-1-vaccinated CD4(-/-) and wild-type mice, not CD8(-/-) mice, were completely protected against Brucella challenge. Determination of cytokines responsible for conferring protection showed the relative importance of IFN-?, but not interleukin-17 (IL-17). Unlike wild-type (wt) mice, IL-17 was greatly induced in IFN-?(-/-) mice, but IL-17 could not substitute for IFN-?'s protection, although an increase in brucellae dissemination was observed upon in vivo IL-17 neutralization. These results show that nasal ?znuA B. melitensis vaccination represents an attractive means to stimulate systemic and mucosal immune protection via CD8(+) T-cell engagement.

Dataset Information

The neglected challenge: Vaccination against rickettsiae.

Publications

The neglected challenge: Vaccination against rickettsiae.

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