Sterilizing immunity against experimental Helicobacter pylori infection is challenge-strain dependent

The development of a murine model of Helicobacter pylori infection through serial in vivo passage of candidate strains has enabled a quantitative assessment of vaccine efficacy. In this study we compare infection with and protection against challenge from both CagA⁺ type I, and CagA⁻ type II in vivo adapted isolates. In vivo passage of a type II H. pylori isolate resulted in a highly infectious strain (X47-2AL), capable of reproducibly infecting mice to high density (10⁷ CFU/g of gastric tissue). Similarly adapted type I strains were found to colonize mice at a significantly lower level (10⁴–10⁵ CFU/g tissue). Mucosal immunization with recombinant urease (rUre) significantly protected animals against both types. Protection against X47-2AL was characterized by a ≥100-fold (or 2 log) reduction in bacterial density. However, the presence of a residual infection highlighted the inability to achieve sterilizing immunity against this strain. The level of protection appeared independent of challenge dose, and was stable for up to 6 months, all animals exhibiting a low-level residual infection that did not recrudesce with time. Similarly immunized mice challenged with isolates representing the residual infection were also protected, confirming that they did not represent a sub-population of H. pylori that could escape immunity. Immunization and challenge studies with type I adapted-isolates, demonstrated a similar 2–3 log reduction in the bacterial burden, but that in this instance resulted in sterilizing immunity. These results suggest varied specificity for the murine host by different Helicobacter strains that can influence the outcome of both infection and immunity.     

Vaccination with a defined Francisella tularensis subsp. novicida pathogenicity island mutant (ΔiglB) induces protective immunity against homotypic and heterotypic challenge

Francisella tularensis, an intracellular Gram-negative bacterium, is the causative agent of tularemia and a potential bioweapon. Currently, there is no licensed vaccine against this organism. We have characterized the efficacy of a defined F. tularensis subsp. novicida mutant (ΔiglB) as a live attenuated vaccine against pneumonic tularemia. Replication of the iglB mutant (KKF235) in murine macrophages was significantly lower than the wild type novicida strain U112, and exhibited an LD₅₀ greater than 10⁶-fold (>10⁷ CFU vs <10 CFU) in an intranasal challenge model. Mice immunized with KKF235 intranasally or orally induced robust antigen-specific splenic IFN-γ recall responses, as well as the production of systemic and mucosal antibodies. Intranasal vaccination with KKF235 protected mice from subsequent homotypic challenge with U112 as well as heterotypic challenge with F. tularensis subsp. holarctica (LVS). Moreover, protected animals also exhibited minimal pathological changes compared with mock-vaccinated and challenged animals. The protection conferred by KKF235 vaccination was shown to be highly dependent on endogenous IFN-γ production. Most significantly, oral immunization with KKF235 protected mice from a highly lethal subsp. tularensis (SCHU S4) pulmonary challenge. Collectively, these results further suggest the feasibility of using defined pathogenicity island mutants as live vaccine candidates against pneumonic tularemia.     

Strain-specific protective immunity following vaccination against experimental Trypanosoma cruzi infection

Immunisation with Amastigote Surface Protein 2 (asp-2) and trans-sialidase (ts) genes induces protective immunity in highly susceptible A/Sn mice, against infection with parasites of the Y strain of Trypanosoma cruzi. Based on immunological and biological strain variations in T. cruzi parasites, our goal was to validate our vaccination results using different parasite strains. Due to the importance of the CD8⁺ T cells in protective immunity, we initially determined which strains expressed the immunodominant H-2K^k-restricted epitope TEWETGQI. We tested eight strains, four of which elicited immune responses to this epitope (Y, G, Colombian and Colombia). We selected the Colombian and Colombia strains for our studies. A/Sn mice were immunised with different regimens using both T. cruzi genes (asp-2 and ts) simultaneously and subsequently challenged with blood trypomastigotes. Immune responses before the challenge were confirmed by the presence of specific antibodies and peptide-specific T cells. Genetic vaccination did not confer protective immunity against acute infection with a lethal dose of the Colombian strain. In contrast, we observed a drastic reduction in parasitemia and a significant increase in survival, following challenge with an otherwise lethal dose of the Colombia strain. In many surviving animals with late-stage chronic infection, we observed alterations in the heart's electrical conductivity, compared to naive mice. In summary, we concluded that immunity against T. cruzi antigens, similar to viruses and bacteria, may be strain-specific and have a negative impact on vaccine development.     

The association between <Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection and adult height

Objectives: A cross-sectional survey was performed to evaluate the association between H. pylori and adult height. Methods: H. pylori infection was assessed using a ¹³C-urea breath test and height measured by a research nurse using a stadiometer in participants between the ages of 40–49 years. Results: Height was measured in 2932/3682 participants that attended and were evaluable. H. pylori infected women were 1.4 cm shorter than uninfected women (95% confidence interval, CI=0.7–2.1 cm) and this statistically significant difference persisted after adjusting for age, ethnicity, childhood and present socio-economic status (H. pylori positives 0.79 cm shorter; 95%CI: 0.05–1.52 cm). H. pylori positive men were 0.7 cm shorter than uninfected men but this did not reach statistical significance (95% CI: −0.1–1.5 cm). Conclusion: Although H. pylori infection is associated with reduced adult height in women, this maybe due to residual confounding.This revised version was published online in July 2005 with corrections to the author group.     

Helicobacter pylori colonization and diarrhoeal illness: results of a population-based cross-sectional study in adults

It has been suggested that Helicobacter pylori colonization may protect against diarrhoeagenic gastrointestinal infections. The aim of this analysis was to investigate the association between H. pylori infection and the frequency of diarrhoeal episodes among adults. Helicobacter pylori infection status was determined by ¹³C-urea breath test. Overall, 784 adults (mean age: 48.7 ± 17.7; range 18–85 years) who participated in two epidemiological studies were included in the analysis. Overall H. pylori prevalence was 25.5%. Episodes of diarrhoea within prior 3 months were less often reported for H. pylori infected subjects compared with H. pylori negative subjects (40.2 vs. 51.6%, p = 0.016). Compared to H. pylori negative subjects the odds ratio (OR) for the occurrence of diarrhoea within the prior 3 months was 0.63 (95% CI: 0.45–0.87) for H. pylori infected subjects. After adjustment for covariates the OR was 0.67 (95% CI: 0.47–0.95). These results support the hypothesis that colonization with H. pylori may protect from gastrointestinal infections that cause diarrhoea.     

A recombinant bivalent fusion protein rVE confers active and passive protection against Yersinia enterocolitica infection in mice

In the present study, a bivalent chimeric protein rVE comprising immunologically active domains of Yersinia pestis LcrV and YopE was assessed for its prophylactic abilities against Yersinia enterocolitica O:8 infection in murine model. Mice immunized with rVE elicited significantly higher antibody titers with substantial contribution from the rV component (3:1 ratio). Robust and significant resistance to Y. enterocolitica infection with 100% survival (P < 0.001) was seen in rVE vaccinated mice when intra peritoneal (I.P.) challenged with 10⁸ CFU of Y. enterocolitica O:8 against the 75%, 60% and 75% survival seen in mice immunized with rV, rE, rV + rE, respectively. Macrophage monolayer supplemented with anti-rVE polysera illustrated efficient protection (89.41% survival) against challenge of Y. enterocolitica O:8. In contrast to sera from sham-immunized mice, immunization with anti-rVE polysera provided complete protection to BALB/c mice against I.P. challenge with 10⁸ CFU of Y. enterocolitica O:8 and developed no conspicuous signs of infection in necropsy. The histopathological analysis of microtome sections confirmed significantly reduced lesion size or no lesion in liver and intestine upon infection in anti-rVE immunized mice. The findings from this study demonstrated the fusion protein rVE as a potential candidate subunit vaccine and showed the functional role of antibodies in protection against Y. enterocolitica infections.     

Effect of black tea aqueous non-dialysate on<Emphasis Type="Italic">Helicobacter pylori</Emphasis> infection in Mongolian gerbils

Objectives  Recently, the appearance ofHelicobacter pylori (H. pylori) resistant to antibiotics has been reported. The development of an antibiotic therapy which would not induce resistant strains ofH. pylori is anticipated. In the present study, the antibiotic effect of black tea aqueous non-dialysate (BTND), the fraction different from tea catechins, onH. pylori was investigated using Mongolian gerbils infected withH. pylori. Methods  BTND was extracted from black tea leaves. A 0.1 w/v% solution of BTND or green tea catechins (GTC) was provided as drinking water to male NGS/Sea Mongolian gerbils infected withH. pylori (ATCC43504) for two weeks. Their stomachs were then excised, the mucosal surfaces were macroscopically observed, and colony forming units (CFU) ofH. pylori were counted. The data were compared between the BTND and GTC groups. Results  The CFU ofH. pylori were significantly decreased by intake of BTND. The body weight of the animals tended to be larger in the group supplied with BTND than in that supplied with GTC. Gastric mucosal injury tended to be smaller in the animals supplied with BTND than in those with GTC. Conclusions  These results suggest that BTND may have an inhibitory effect onH. pylori infection.     

CD8 T cell immunity to Plasmodium permits generation of protective antibodies after repeated sporozoite challenge

Individuals living in malaria endemic areas are subject to repeated infections yet fail to develop sterilizing immunity, however, immunization of mice with attenuated sporozoites or subunit vaccines has shown the ability to protect mice against a sporozoite challenge. We recently reported that mice primed with dendritic cells coated with the dominant circumsporozoite CD8 T cell epitope from Plasmodium berghei followed by a boost with recombinant Listeria monocytogenes expressing the same epitope exhibited sterile immunity against a sporozoite challenge for more than one year. In this report we show those mice do not contain protective antibodies and that depletion of CD4 T cells in the immunized mice did not affect sterile immunity. In contrast, CD8 T cell depletion eliminated protection. Thus, protective immunity generated by this immunization approach is entirely memory CD8 T cell-dependent. We also show here that mice initially protected by circumsporozoite-specific memory CD8 T cells develop sterilizing sporozoite-specific antibodies after repeated asymptomatic challenges with physiologic numbers of viable sporozoites. Therefore, initial protection by a CD8 T cell-targeted liver stage subunit vaccine allows the generation of enhanced sterilizing immune responses from repeated exposure to Plasmodium parasites.     

Protection studies following bronchopulmonary and intramuscular immunisation with Yersinia pestis F1 and V subunit vaccines coencapsulated in biodegradable microspheres: a comparison of efficacy

We have compared the ability of intramuscularly and intratracheally administered recombinant F1 and V subunit antigens to safeguard mice from a lethal systemic challenge with plague. The combined subunits (1μg V plus 5 μg F1) were inoculated either in the ‘free’ state as a solution, or entrapped within microspheres composed of a biodegradable polyester (Poly- -lactide), on day 1 and 60 of the experiment. In comparison to the other regimens, introduction of microsphere suspensions into the respiratory tract resulted in statistically elevated levels of specific immunoglobulins in day 82 lung wash samples. A subcutaneous challenge with virulent Yersinia pestis bacteria on day 137, equivalent to more than 10⁵ mouse LD₅₀s, was comparatively well tolerated by all subunit treatment groups (with survival rates between 66 and 90%). In contrast, 80% of the mice injected intramuscularly with soluble F1 and V were defeated by a 10⁷ MLD₅₀ subcutaneous challenge, whereas the group immunised intramuscularly with microparticles were significantly better protected (p<0.1) with 50% survival. Similarly, mice immunised intratracheally with microparticles were significantly better safeguarded (56% survival) compared with the group immunised with soluble subunits intramuscularly (p<0.01). Soluble sub-units delivered intratracheally afforded 33% protection against 10⁷ MLD₅₀s. These data indicate that bronchopulmonary administration of microsphere co-encapsulated recombinant F1 and V antigens elicits a similar level of protective immunity against systemic plague infection as that evoked by injecting co-encapsulated subunits into the muscle. Such findings corroborate the thesis that introduction of appropriately formulated F1 and V subunits into the respiratory tract may be an alternative to parenteral immunisation schedules for protecting individuals from plague.     

CD8+ T cells specific to a single Yersinia pseudotuberculosis epitope restrict bacterial replication in the liver but fail to provide sterilizing immunity

CD8⁺ T cells use contact-dependent cytolysis of target cells to protect the host against intracellular pathogens. We have previously shown that CD8⁺ T cells and perforin are required to protect against the extracellular pathogen Yersinia pseudotuberculosis. Here we establish an experimental system where CD8⁺ T cells specific to a single model antigen are the only memory response present at time of challenge. Using mice immunized with a vaccine strain of Listeria monocytogenes that expresses secreted ovalbumin (Lm-OVA), we show that OVA-specific CD8⁺ T cells are generated and provide limited protection against challenge with virulent OVA⁺ Y. pseudotuberculosis. Perforin expression by OVA-specific CD8⁺ T cells was required, as Lm-OVA-immunized perforin-deficient mice showed higher bacterial burden as compared to Lm-OVA-immunized perforin-sufficient mice. Surprisingly, antigen-specific T cell protection waned over time, as Lm-OVA-immune mice eventually succumbed to Yersinia infection. Kinetic analysis of infection in mice with and without OVA-specific CD8⁺ T cells revealed that bacterial numbers increased sharply in OVA-naïve mice until death, while OVA-immune mice held bacterial burden to a lower level throughout the duration of illness until death. Clonal analysis of bacterial populations in OVA-naïve and OVA-immune mice at distinct time points revealed equivalent and severe bottle-neck effects for bacteria in both sets of mice immediately after intravenous challenge, demonstrating a dominant role for other aspects of the immune system regardless of CD8⁺ T cell status. These studies indicate that CD8⁺ T cells against a single antigen can restrict Y. pseudotuberculosis colonization in a perforin-dependent manner, but ultimately are insufficient in their ability to provide sterilizing immunity and protect against death.     

A ML29 reassortant virus protects guinea pigs against a distantly related Nigerian strain of Lassa virus and can provide sterilizing immunity

Lassa virus (LASV) is responsible for the deaths of thousands of people in West Africa annually. Genetic diversity among LASV strains is the highest among the Arenaviridae and represents a great challenge for vaccine development. Guinea pigs vaccinated with a ML29 reassortant vaccine experienced sterilizing immunity and complete protection when challenged on day 30 either with homologous virus or with the distantly related Nigerian isolate. Simultaneous vaccination-challenge or challenge on day 2 after vaccination also protected 60-100% of the animals against both strains, but without sterilizing immunity. These results indicate that simultaneous replication of ML29 and LASV attenuates the virulence of LASV infection.     

Virulence factors and O groups of Escherichia coli isolates from patients with acute pyelonephritis, cystitis and asymptomatic bacteriuria

The relationship between the presence of bacterial virulence factors and the severity of urinary tract infection (UTI) was analized in this study. The production of -hemolysin (Hly), the expression of P-fimbriae and the mannose-resistant hemagglutination (MRHA) type IVa (associated with the presence of P-fimbriae), were all detected more frequently in Escherichia coli strains from acute pyelonephritis than in strains isolated from cystitis and asymptomatic bacteriuria. In contrast, the production of cytotoxic necrotizing factor type 1 (CNF1) and the expression of MRHA types III and IVb were distributed uniformly between strains causing different clinical categories of UTI. Thus 88% of the E. coli strains from acute pyelonephritis showed some of the virulence factors investigated in this study, whereas only 60% (p < 0.01) and 56% (p < 0.01) repectively of the strains isolated from cystitis and asymptomatic bacteriuria possessed virulence factors. There were no significant differences in the prevalence of virulence properties between strains isolated from patients with or without complicating factors. Only 16% (p < 0.001) of the fecal isolates from healthy individuals showed virulence factors. The virulence factors were concentrated in strains belonging to 10 (O1, O2, O4, O6, O7, O14, O18, O22, O75 and 083) of the 12 serogroups most frequently detected in uropathogenic E.coli strains. The majority of uropathogenic O4, O6, O14, O22, O75 and O83 E.coli strains were Hly⁺CNF1⁺ and expressed P-fimbriae or MRHA type III, whereas the strains of serogroup O18 were Hly⁺CNFI^– and P-fimbriated. Among O1 and O7 strains we found Hly^– CNF1^–strains that expressed P-fimbriae. Among O2 strains we found Hly⁺CNF1⁺ strains that expressed P-fimbriae or MRHA type III and other Hly^–CNF1^–strains that possessed P-fimbriae. We conclude that E.coli strains isolated from pyelonephritis show virulence factors more frequently than those from cystitis and asymptomatic bacteriuria, and that strains that cause urinary tract infections in Spain belong to the same serogroups as uropathogenic E.coli isolated in other areas of the world. Our results support the special pathogenicity theory and suggest that many cases of serious urogenital disease may be caused by a limited number of P-fimbriated E.coli strains that usually produce -hemolysin.     

Preclinical immunogenicity and protective efficacy of an oral Helicobacter pylori inactivated whole cell vaccine and multiple mutant cholera toxin: A novel and non-toxic mucosal adjuvant

Mucosal vaccines against Helicobacter pylori consisting of either whole cell bacteria or recombinant antigens can induce immune protection against challenge in mice only when co-administrated with a strong mucosal adjuvant such as cholera toxin (CT) or Escherichia coli heat labile enterotoxin (LT). The strong enterotoxicity of these adjuvants however preclude their use in human vaccines. The recently developed multiple mutant CT (mmCT) is a strong, yet practically non-toxic novel mucosal adjuvant which here was admixed with a formalin-inactivated H. pylori whole cell vaccine (WCV) as a potential vaccine candidate against H. pylori infection. We report that intragastric immunizations with H. pylori WCV together with mmCT, similar to immunization with WCV together with CT, resulted in 50–125-fold reduction in colonization of H. pylori in the stomach of mice associated with rises in both serum IgG and intestinal-mucosal IgA anti-H. pylori antibody responses and strong T cell and IFNγ and IL-17A cytokine responses. Data presented in this study also supports that the proposed vaccine can be grown in a bioreactor and would be effective against infection caused by a multitude of pathogenic H. pylori strains isolated from patients from various continents. The results warrant immunization studies in humans to evaluate the safety, immunogenicity and efficacy of the proposed H. pylori WCV and mmCT.     

Immunogenicity of attenuated measles virus engineered to express Helicobacter pylori neutrophil-activating protein

Helicobacter pylori is a Gram-negative, spiral-shaped microorganism associated with acute and chronic gastritis, peptic ulcer, gastric cancer and gastric lymphomas in humans. H. pylori neutrophil-activating protein (NAP) is a major virulence factor playing a central role in pathogenesis of mucosal inflammation by immune cell attraction and Th1 cytokine response polarization. NAP is protective antigen and promising vaccine candidate against H. pylori infection. Here we present the development of measles virus (MV) vaccine strain encoding the NAP antigen. In order to facilitate the extracellular transport and detection, NAP was inserted in the human lambda immunoglobulin chain replacing a major part of the variable domain. We generated two MV vectors expressing secretory NAP forms: MV-lambda-NAP encoding the full-length constant lambda light chain domain and MV-s-NAP encoding only the N-terminus of the lambda light chain with the leader peptide. Immunization of MV permissive Ifnarko-CD46Ge transgenic mice by a single intraperitoneal injection of the NAP-expressing strains induced a robust, long-term humoral and cellular immune response against MV. Nine months post vaccination measles-neutralizing antibody titers were above the serum level considered protective for humans. Furthermore, all animals immunized with MV strains expressing the secretory NAP antigen developed strong humoral immunity against NAP, reaching titers >1:10,000 within 2-4 weeks. IFN-γ ELISpot assay confirmed that NAP-encoding MV vectors can also stimulate NAP-specific cell-mediated immunity. Our data demonstrate that MV is an excellent vector platform for expression of bacterial antigens and development of vaccines for H. pylori immunoprophylaxis in humans.     

Role of MHC class Ib molecule,H2-M3 in host immunity against tuberculosis

The MHC class I family comprises both classical (class Ia) and non-classical (class Ib) members. While the prime function of classical MHC class I molecules (MHC class Ia) is to present peptide antigens to pathogen-specific cytotoxic T cells, non-classical MHC-I (MHC class Ib) antigens perform diverse array of functions in both innate and adaptive immunity. Vaccines against intracellular pathogens such as Mycobacterium tuberculosis need to induce strong cellular immune responses. Recent studies have shown that MHC class I molecules play an important role in the protective immune response to M. tuberculosis infection. Both MHC Ia-restricted and MHC class Ib-restricted M. tuberculosis -reactive CD8⁺ T cells have been identified in humans and mice, but their relative contributions to immunity is still uncertain. Unlike MHC class Ia-restricted CD8⁺ T cells, MHC class Ib-restricted CD8⁺ T cells are constitutively activated in naive animals and respond rapidly to infection challenge, hence filling the temporal gap between innate and adaptive immunity. The present review article summarizes the general host immunity against M. tuberculosis infection highlighting the possible role of MHC class Ib molecule, H2-M3 and their ligands (N-formylated peptides) in protection against tuberculosis.     

B. melitensis rough strain B115 is protective against heterologous Brucella spp. infections

Brucellosis is one of the most serious zoonoses all over the world, with B. melitensis, B. abortus and B. suis being the most pathogenic species for humans. Vaccination of domesticated livestock still represents the most efficient way to prevent human infection. However, the available Brucella vaccines retain an important residual virulence and induce antibodies interfering with surveillance programs. Moreover, each vaccine shows different protective effects versus different Brucella species and different animal hosts.Nowadays, while B. melitensis and B. suis infections in cattle are emerging as a significant problem, there are no available vaccines to overcome such issue.B. melitensis strain B115, a natural, attenuated rough strain in our previous studies proved to be highly protective against B. melitensis and B. ovis infections in mice, without inducing interfering antibodies. In this study, we tested the efficiency of B115 as vaccine against B. abortus and B. suis. Vaccination of mice with 10⁸ CFU/mouse of B. melitensis B115 conferred a satisfactory protection against B. abortus 2308. On the contrary, mice vaccinated once with 10⁸ or 10⁹ CFU/mouse of B115 were weakly protected against B. suis infection. Conversely, when mice were vaccinated twice with 10⁹ CFU B115/mouse, the protective activity significantly increased. Unlike its rough phenotype, B115 showed an adequate persistence in mice accompanied to a solid humoral and cell-mediated immunity. All together, these findings suggest the potential usefulness of B115 to control brucellosis in animal hosts due to heterologous challenges.     

A novel liposome adjuvant DPC mediates Mycobacterium tuberculosis subunit vaccine well to induce cell-mediated immunity and high protective efficacy in mice

Tuberculosis (TB) is a serious disease around the world, and protein based subunit vaccine is supposed to be a kind of promising novel vaccine against it. However, there is no effective adjuvant available in clinic to activate cell-mediated immune responses which is required for TB subunit vaccine. Therefore, it is imperative to develop new adjuvant. Here we reported an adjuvant composed of dimethyl dioctadecylammonium (DDA), Poly I:C and cholesterol (DPC for short). DDA can form a kind of cationic liposome with the ability to deliver and present antigen and can induce Th1 type cell-mediated immune response. Poly I:C, a ligand of TLR3 receptor, could attenuate the pathologic reaction induced by following Mycobacterium tuberculosis challenge. Cholesterol, which could enhance rigidity of lipid bilayer, is added to DDA and Poly I:C to improve the stability of the adjuvant. The particle size and Zeta-potential of DPC were analyzed in vitro. Furthermore, DPC was mixed with a TB fusion protein ESAT6-Ag85B-MPT64(190-198)-Mtb8.4-Rv2626c (LT70) to construct a subunit vaccine. The subunit vaccine-induced immune responses and protective efficacy against M. tuberculosis H37Rv infection in C57BL/6 mice were investigated. The results showed that the DPC adjuvant with particle size of 400 nm and zeta potential of 40 mV was in good stability. LT70 in the adjuvant of DPC generated strong antigen-specific humoral and cell-mediated immunity, and induced long-term higher protective efficacy against M. tuberculosis infection (5.41 ± 0.38 log₁₀ CFU) than traditional vaccine Bacillus Calmette–Guerin (BCG) (6.01 ± 0.33 log₁₀ CFU) and PBS control (6.53 ± 0.26 log₁₀ CFU) at 30 weeks post-vaccination. In conclusion, DPC would be a promising vaccine adjuvant with the ability to stimulate Th1 type cell-mediated immunity, and could be used in TB subunit vaccine.     

Peritoneal B-1b and B-2 B-cells confer long-term protection from pneumococcal serotype 3 infection after vaccination with Prevnar-13 and are defective in sickle cell disease mice

Long-term immunity after inoculation with the pneumococcal conjugate vaccine (Prevnar-13) is impaired in sickle cell disease (SCD) mice. We sought to determine which B-cell subsets are defective in SCD mice after vaccination with Prevnar-13, yet confer long-term immunity in wild-type (WT) mice. We vaccinated WT and SCD mice three times at three week intervals with Prevnar-13. Fourteen weeks later, 5 1 10⁴ cells of isolated peritoneal B-1a, B-1b, and B-2 cells were harvested and intraperitoneally transferred to Rag −/− recipients. A week later recipients were intraperitoneally challenged with 10³ CFU of Streptococcus pneumoniae (serotype 3). Recipient mice that received either B-1b or B-2 B-cells from WT mice survived challenge, whereas mice that received B-1a cells died. Recipient mice that received B-1a, B-1b, or B-2 cells from SCD mice died after challenge. Both B-1b and B-2 cells appear to confer long-term immunity after Prevnar-13 vaccination, yet neither subset functions properly in SCD mice.     

Colombia: the widening gap between health care reform and gastric cancer

The purpose of this paper is to discuss Colombia’s recent health care reform and subsequent social implications regarding gastric cancer, which is a common cancer in Colombia. This review explores the use of Helicobacter pylori prevalence classifying as an indicator of failing implementation of health policy, specifically H. pylori should be explored in the context of socioeconomic inequity. A review of the literature examining recent Colombian health care reform and H. pylori infection was conducted. H. pylori occur most frequently in impoverished populations. Gastric cancer (GC) is the main cause of mortality by cancer in Colombia, a South American country, which has a high prevalence of H. pylori in the population. Over the past 40 years, Colombia has undergone a revolutionary improvement in the health and social status of its population. In recent times, the country has faced a unique challenge as its government has grappled with the ongoing civil war with numerous war rebels. It is known that socioeconomic conditions, known to influence gastric cancer risk, are important determinants of H. pylori infection. The role of socioeconomic gradients in developing countries should be emphasized as a basis for etiological research; the disparity between the wealthy and poor is increasing over time. Colombia is currently undergoing major changes in disease-specific mortality rates, including an increasing burden of cancer death.     

Vaccination of Fischer 344 rats against pulmonary infections by Francisella tularensis type A strains

Pneumonic tularemia caused by inhalation of the type A strains of Francisella tularensis is associated with high morbidity and mortality in humans. The only vaccine known to protect humans against this disease is the attenuated live vaccine strain (LVS), but it is not currently registered for human use. To develop a new generation of vaccines, multiple animal models are needed that reproduce the human response to F. tularensis infection and vaccination. We examined the potential use of Fischer 344 rat as such a model. Fischer 344 rats were very sensitive to intratracheal infection with the virulent type A strain SCHU S4 and generally succumbed less than 2 weeks after infection. Similar to humans and non-human primates, Fischer 344 rats vaccinated with LVS by subcutaneous or intradermal routes were protected against a greater range of respiratory SCHU S4 challenge doses than has been reported for LVS vaccinated mice. Intratracheal LVS vaccination also induced effective immunity, but it was less protective when the challenge dose exceeded 10⁵ SCHU S4. LVS vaccination did not prevent SCHU S4 infection but rather controlled bacterial growth and pathology, leading to the eventual clearance of the bacteria. Our results suggest that the Fischer 344 rat may be a good model for studying pneumonic tularemia and evaluating potential vaccine candidates.