Mucosal immunisation of mice with malaria protein on lactic acid bacterial cell walls

Moorthy, Guhapriya; Ramasamy, Ranjan

doi:10.1016/j.vaccine.2007.01.070

Cited by 19 publications

(15 citation statements)

References 32 publications

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“…However, public fear of using an attenuated pathogen as a vaccine carrier has deterred its acceptance. Recent studies have shown that oral administration of a number of lactobacilli expressing recombinant immunogens induces local mucosal (42) and systemic antibody responses (62). Other studies have explored this further and showed that immune responses induced via lactobacilli delivered through oral vaccination confer some protection against challenge with the respective pathogen (27,31,32,60).…”

Section: Discussionmentioning

confidence: 99%

Oral Immunization with RecombinantLactobacillus plantarumInduces a Protective Immune Response in Mice with Lyme Disease

Río

Dattwyler

Aroso

et al. 2008

Clin Vaccine Immunol

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Mucosal immunization is advantageous over other routes of antigen delivery because it can induce both mucosal and systemic immune responses. Our goal was to develop a mucosal delivery vehicle based on bacteria generally regarded as safe, such as Lactobacillus spp. In this study, we used the Lyme disease mouse model as a proof of concept. We demonstrate that an oral vaccine based on live recombinant Lactobacillus plantarum protects mice from tick-transmitted Borrelia burgdorferi infection. Our method of expressing vaccine antigens in L. plantarum induces both systemic and mucosal immunity after oral administration. This platform technology can be applied to design oral vaccine delivery vehicles against several microbial pathogens.Lactic acid bacteria are naturally associated with mucosal surfaces, particularly the gastrointestinal tract, and are also indigenous to food-related habitats, including plants, wine, milk, and meat. These gram-positive bacteria include both important pathogens, e.g., several Streptococcus species, and extremely valuable nonpathogenic species that have been used since ancient times for food and feed fermentation (11,37,58). The host is highly adapted to the presence of commensal intestinal bacteria (36). There is evidence that some strains of lactic acid bacteria have a favorable influence on physiologic and pathological processes of the host due to their specific health-promoting probiotic characteristics that relate to modulation of the immune system (15,36,41). Some strains of lactic acid bacteria polarize the naïve immune system by skewing it toward Th1 responses (41, 56).There have been a number of reports of oral vaccine candidates established from genetically modified pathogenic bacteria, such as Salmonella and Listeria species (1, 2, 30, 45, 52), or commensal bacteria, such as Lactococcus lactis and Lactobacillus species (27,31,32,60). The latter are food-grade bacteria that have GRAS status (generally regarded as safe). While both pathogenic and commensal bacteria have advantages and disadvantages as mucosal delivery vehicles, lactic acid bacteria are preferable in terms of safety and a lower risk of side effects (27,47). Presentation of antigens on the surface of lactobacilli is attractive for vaccine design, especially because the peptidoglycan layer of some strains appears to exhibit natural immuno-adjuvanticity (33,35,44,46). Thus, these species are excellent candidates for the development of safe mucosal delivery vehicles of prophylactic and therapeutic molecules. Of the Lactobacillus strains previously used for vaccine delivery, we chose L. plantarum because there is evidence that this strain is a better agent for vaccination with tetanus toxin fragment C (TTFC) than L. casei or L. lactis (22,53).Lyme disease is the most prevalent vector-borne infectious disease in the United States. A vaccine administered via needle inoculation and based on outer surface protein A (OspA) has proved effective in preventing Borrelia burgdorferi infection in animals and humans (7,10,(16)(17)...

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Section: Discussionmentioning

confidence: 99%

Oral Immunization with RecombinantLactobacillus plantarumInduces a Protective Immune Response in Mice with Lyme Disease

Río

Dattwyler

Aroso

et al. 2008

Clin Vaccine Immunol

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“…ELISPOT assay: At 14 days post final immunization, the mesenteric lymph nodes (MLN), spleen (SP) and Peyer's patches (PP) of mice (n=3) from each group were removed and disrupted by sterile gauze as previously described [12,14]. The results are expressed as the number of antigenspecific ASCs per 10 7 cells.…”

Section: Preparation Of Recombinant L Lactis For Immunization: Lmentioning

confidence: 99%

Subcutaneous or Oral Immunization of Mice with <i>Lactococcus lactis</i> Expressing F4 Fimbrial Adhesin FaeG

Liu

et al. 2013

The Journal of Veterinary Medical Science

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ABSTRACT. Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of diarrhea in neonatal and postweaning piglets. Fimbrial adhesion of ETEC has been considered an important colonization factor with antigenicity. To safely and effectively deliver the F4 (K88) fimbrial adhesin FaeG to the immune system, we have previously constructed the secretory expression vector pNZ8112-faeG, and FaeG was produced in cytoplasmic form in Lactococcus lactis. In this work, BALB/c mice were immunized with recombinant L. lactis to further determine the immunogenicity of recombinant FaeG (rFaeG) via the subcutaneous or oral route. Subcutaneous immunization in mice with recombinant L. lactis induced a significant increase in the F4-specific serum IgG titer and the number of antibody-secreting cells (ASCs) in the spleen. Oral immunization of mice with recombinant L. lactis induced mucosal and systemic F4-specific immune responses and increased the number of ASCs in the spleen, mesenteric lymph nodes and Peyer's patches. High-dose (2.8 × 10 11 CFU) recombinant strains and adjuvant cholera toxin B subunit enhanced specific mucosal immune responses. The results suggest the feasibility of delivering rFaeG expressed in L. lactis to the immune system in order to induce an F4-specific immune response. Diarrhea induced by F4 enterotoxigenic Escherichia coli (ETEC) in neonatal and weaned piglets results in severe economic losses due to the high mortality caused by infections [24]. F4 fimbriae are a primary virulence factor of ETEC and enable the bacteria to attach to F4-specific receptors (F4R) on the brush border of intestinal enterocytes [18]. Consequently, ETEC produces enterotoxins and causes piglet diarrhea. The F4 fimbriae of ETEC are composed of a repeating major subunit, FaeG and some minor subunits [23]. Since FaeG has both adhesive and antigenic properties, the development of anti-adhesive vaccines to prevent ETEC infections has long been pursued by researchers [16,17,22].An effective vaccine is crucial for neonatal and weaned piglets to evoke protective immunity against ETEC. Oral administration of antigens can induce intestinal mucosal immune responses to produce an abundance of secretory IgA (sIgA) antibodies that play an important role [7,19]. Therefore, oral immunization is thought to an effective measure against ETEC infections during the postweaning period [22]. However, parenteral vaccination could be more appropriate for suckling piglets, because of mucosal immune system difficultly stimulated during the suckling period by the oral route [21]. Therefore, different immune strategies should be taken according to the stage of piglet weaning.Lactococcus lactis is a Gram-positive lactic acid bacterium that is used to produce fermented foods and generally recognized as safe (GRAS). L. lactis is an attractive candidate for the production and delivery of heterologous proteins to the mucosal immune system [3]. Nonpathogenic and noninvasive L. lactis may be a good alternative to attenuated pathogens as a vaccine vecto...

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“…The second major advantage of this bacterium as a mucosal delivery vehicle is that, in addition to its efficient elicitation of antigen-specific mucosal immune responses, it also reduces the potential side effects common to systemic routes of administration. The immune response elicited against the L. lactis vector itself is only a weak one, while the major immune responses are directed primarily against the heterologously expressed antigens (5,7). Therefore, the possibility of a strong immune response against the vaccine carrier, diminishing the response against the heterologous antigens, is avoided.…”

Section: Introductionmentioning

confidence: 99%

Intranasal immunization with recombinant Lactococci carrying human papillomavirus E7 protein and mouse interleukin-12 DNA induces E7-specific antitumor effects in C57BL/6 mice

Liu

et al. 2013

Oncology Letters

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The use of Lactococcus lactis for the co-delivery of antigens and cytokines has been shown to successfully induce a special immune response. However, it is unknown whether the same results may be triggered through immunization of animals with L. lactis simultaneously carrying protein antigen and cytokine DNA. The present study evaluated the protective effects of intranasally administered live L. lactis strains carrying human papillomavirus 16 E7 protein and murine interleukin-12 (IL-12) DNA (LL-E7P-IL-12D) in a TC-1 tumor animal model. C57BL/6 mice were intranasally immunized with recombinant lactococci, and assays for cytotoxicity measurement and tumor protection were carried out to assess the immunological effects of the vaccine candidates. IL-12 and interferon-γ serum levels were measured and immunization with LL-E7P-IL-12D was shown to induce an E7-specific immune response and to confer protection against TC-1-induced tumors in vivo. Mice in the LL-E7P-IL-12D group showed an 80% survival rate when the control mice had died. Therapeutic immunization with recombinant L. lactis strains 7 days after TC-1 injection led to a reduction in the number of palpable tumors in treated mice. The antitumor effects of the vaccination occurred through an E7-specific cytotoxic T-lymphocyte response. In the present study, the use of a single L. lactis strain, to co-administer protein antigen and adjuvant DNA, successfully induced an antigen-specific immune response. These observations demonstrate a new strategy for the use of L. lactis as a delivery vector of therapeutic molecules and antigens.

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Mucosal immunisation of mice with malaria protein on lactic acid bacterial cell walls

Cited by 19 publications

References 32 publications

Oral Immunization with RecombinantLactobacillus plantarumInduces a Protective Immune Response in Mice with Lyme Disease

Oral Immunization with RecombinantLactobacillus plantarumInduces a Protective Immune Response in Mice with Lyme Disease

Subcutaneous or Oral Immunization of Mice with <i>Lactococcus lactis</i> Expressing F4 Fimbrial Adhesin FaeG

Intranasal immunization with recombinant Lactococci carrying human papillomavirus E7 protein and mouse interleukin-12 DNA induces E7-specific antitumor effects in C57BL/6 mice

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