Kinetics of the mucosal antibody secreting cell response and evidence of specific lymphocyte migration to the lung after oral immunisation with attenuated S. enterica var. typhimurium

Allen, Jack J

doi:10.1016/s0928-8244(99)00204-7

Cited by 5 publications

(4 citation statements)

References 15 publications

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“…Therefore, to examine how current or recent malaria would effect existing vaccine mediated protection against S . Typhimurium, we made use of a mouse model in which protective immunity is induced in the absence of malaria, via administration of a well-characterized live attenuated NTS vaccine (strain BRD509, ΔaroA ΔaroD ) [ 24 – 28 ]. We then interrogated the effect of malaria on established immunity to S .…”

Section: Resultsmentioning

confidence: 99%

Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

et al. 2015

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In immunocompetent individuals, non-typhoidal Salmonella serovars (NTS) are associated with gastroenteritis, however, there is currently an epidemic of NTS bloodstream infections in sub-Saharan Africa. Plasmodium falciparum malaria is an important risk factor for invasive NTS bloodstream in African children. Here we investigated whether a live, attenuated Salmonella vaccine could be protective in mice, in the setting of concurrent malaria. Surprisingly, mice acutely infected with the nonlethal malaria parasite Plasmodium yoelii 17XNL exhibited a profound loss of protective immunity to NTS, but vaccine-mediated protection was restored after resolution of malaria. Absence of protective immunity during acute malaria correlated with maintenance of antibodies to NTS, but a marked reduction in effector capability of Salmonella-specific CD4 and CD8 T cells. Further, increased expression of the inhibitory molecule PD1 was identified on memory CD4 T cells induced by vaccination. Blockade of IL-10 restored protection against S. Typhimurium, without restoring CD4 T cell effector function. Simultaneous blockade of CTLA-4, LAG3, and PDL1 restored IFN-γ production by vaccine-induced memory CD4 T cells but was not sufficient to restore protection. Together, these data demonstrate that malaria parasite infection induces a temporary loss of an established adaptive immune response via multiple mechanisms, and suggest that in the setting of acute malaria, protection against NTS mediated by live vaccines may be interrupted.

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Section: Resultsmentioning

confidence: 99%

Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

et al. 2015

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“…Furthermore, T cells in NALT primed after i.n. immunization could migrate to mucosal effector sites to help IgA B cells to differentiate and mature into plasma cells (1,31). Better understanding of the full mechanisms involved in this process still awaits the clarification of the functional role of the secretory IgG 3 10 3 10 IgM 3 10 3 10 a Mice, 20 per group, were i.n.…”

Section: Discussionmentioning

confidence: 99%

Specific Immune Responses and Enhancement of Murine Pulmonary Clearance of Moraxella catarrhalis by Intranasal Immunization with a Detoxified Lipooligosaccharide Conjugate Vaccine

et al. 2002

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Moraxella catarrhalis is an important human mucosal pathogen. This study investigated the effect of intranasal immunization with a detoxified-lipooligosaccharide-cross-reactive mutant of diphtheria toxin (dLOS-CRM) vaccine candidate on pulmonary clearance following an aerosol challenge of mice with M. catarrhalis. Intranasal immunization with dLOS-CRM plus cholera toxin induced a significantly dose-dependent increase of immunoglobulin A (IgA) and IgG in the nasal wash, lung lavage fluid, saliva, and fecal extract. In addition, serum IgG, IgM, and IgA against LOS of M. catarrhalis were detected. LOS-specific antibody-forming cells were found in the nasal passages, spleens, nasally associated lymphoid tissues, cervical lymph nodes, lungs, and Peyer's patches using an enzyme-linked immunospot assay. The dLOS-CRM vaccine induced a significant bacterial clearance (70 to 90%) of both homologous and heterologous strains in the lungs compared to that observed in the controls (P < 0.01). Intriguingly, intranasal immunization with dLOS-CRM showed a higher level of bacterial clearance compared with subcutaneous injections with dLOS-CRM. These data indicate that dLOS-CRM induces specific mucosal and systemic immunity through intranasal immunization and also provides effective bacterial clearance. On the basis of these results, we believe that dLOS-CRM should undergo continued testing to determine whether it would induce protective immune response in humans.The mucosal surfaces of the respiratory, genitourinary, and gastrointestinal tracts consist of an efficient physical barrier against environmental pathogens. However, a majority of bacterial and viral infections directly affect or enter the body through mucosal surfaces, and colonization at these sites is the first step in pathogenesis. Moraxella catarrhalis is a gram-negative human mucosal pathogen which causes middle ear infections in children as well as lower respiratory tract infections in adults with chronic pulmonary disease (8,9,22,28). In young children, M. catarrhalis is one of the three major causes of otitis media (OM) along with Streptococcus pneumoniae and nontypeable Haemophilus influenzae. More than 80% of children are likely to experience at least one episode of OM by the age of 2 years. Recurrent or chronic OM can lead to hearing, speech, and/or language problems. The estimated cost from OM in the United States is $5 billion annually (23). In the elderly, especially those with chronic obstructive pulmonary diseases, M. catarrhalis can cause severe lower respiratory tract infections such as pneumonia that can be life threatening (38). Currently, the number of antibiotic-resistant strains of M. catarrhalis has significantly increased (4, 13).Active immunization with an effective vaccine would be an efficient approach to prevent such infections (27). Efforts have therefore been made to evaluate surface antigens of M. catarrhalis such as outer membrane proteins (6,11,29,30) and lipooligosaccharide (LOS) as candidate vaccines, which may elicit protective antib...

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“…Best described is the fact that intestinal priming can lead to protection of the lower respiratory tract. It has been well established in animal models (1,17,63,64), and human studies (19,31), that oral immunization can prevent infection of the lung. However, several facts suggest that this protection is not achieved by specific trafficking or homing of lymphocytes to the lower respiratory tract but rather through mostly unspecific mechanisms.…”

Section: Immunological Cross-talk Between Distant Mucosal Compartmentmentioning

confidence: 99%

Upper Respiratory Tract Immunity

Zuercher¹

2003

Viral Immunology

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Most viral infections occur via mucosal surfaces like the respiratory, gastrointestinal, or genital epithelium. The mucosal immune system is an important component of the body's defense against such infections and consequently induction of mucosal, in addition to systemic immunity, might improve vaccine efficacy. Several orally administered vaccines, for example, against poliovirus and gastrointestinal bacterial infections, have been developed and are widely used. In contrast, to date most vaccines against respiratory pathogens are applied parenterally and thus do not induce significant mucosal immunity. For the development of effective mucosal vaccines a more profound understanding of the immune mechanisms operative at mucosal surfaces and of the interplay between different mucosal compartments is needed. Moreover, factors like the dose, form of application, and type of mucosal adjuvants are critical to the induction of effective mucosal immunity. This brief review will focus mainly on the nasal route and will summarize some recent findings concerning the function of the mucosal immune system of the upper respiratory tract. Furthermore, routes of cross-immunization between distinct mucosal compartments and how they might be relevant to vaccine development will be addressed. Finally, I will outline critical factors for the rational design of nasal vaccines and in this context highlight some recent preclinical and clinical developments in the field.

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Kinetics of the mucosal antibody secreting cell response and evidence of specific lymphocyte migration to the lung after oral immunisation with attenuated S. enterica var. typhimurium

Cited by 5 publications

References 15 publications

Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

Transient Loss of Protection Afforded by a Live Attenuated Non-typhoidal Salmonella Vaccine in Mice Co-infected with Malaria

Specific Immune Responses and Enhancement of Murine Pulmonary Clearance of Moraxella catarrhalis by Intranasal Immunization with a Detoxified Lipooligosaccharide Conjugate Vaccine

Upper Respiratory Tract Immunity

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