IgA Antibodies In Saliva Research Articles

Molecular Events in Immune Responses to Sublingual Influenza Vaccine with Hemagglutinin Antigen and Poly(I:C) Adjuvant in Nonhuman Primates, Cynomolgus Macaques.

Sublingual vaccines offer the benefits of inducing mucosal immunity to protect against respiratory viruses, including Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and influenza, while also enabling needle-free self-administration. In a previous study, a sublingual SARS-CoV-2 vaccination was created by combining a recombinafigureCoV-2 spike protein receptor-binding domain antigen with a double strand RNA Poly(I:C) adjuvant. This vaccine was tested on nonhuman primates, Cynomolgus macaques. This study examined the immune and inflammatory responses elicited by the sublingual influenza vaccine containing hemagglutinin (HA) antigen and Poly(I:C) adjuvants, and assessed the safety of this vaccine in nonhuman primates. The Poly(I:C)-adjuvanted sublingual vaccine induced both mucosal and systemic immunities. Specifically, the sublingual vaccine produced HA-specific secretory IgA antibodies in saliva and nasal washings, and HA-specific IgA and IgG were detected in the blood. This vaccine appeared to be safe, as judged from the results of blood tests and plasma C-reactive protein levels. Notably, sublingual vaccination neither increased the production of inflammation-associated cytokines-IFN-alpha, IFN-gamma, and IL-17-in the blood, nor upregulated the gene expression of proinflammatory cytokines-IL12A, IL12B, IFNA1, IFNB1, CD69, and granzyme B-in white blood cells. Moreover, DNA microarray analyses revealed that sublingual vaccination evoked both enhancing and suppressing expression changes in genes associated with immune-related responses in cynomolgus monkeys. Therefore, the sublingual vaccine with the Poly(I:C) adjuvant is safe, and creates a balanced state of enhancing and suppressing the immune-related response.

Evaluation of the humoral and mucosal immune response of a multiepitope vaccine against COVID-19 in pigs.

This study evaluated the immune response to a multiepitope recombinant chimeric protein (CHIVAX) containing B- and T-cell epitopes of the SARS-CoV-2 spike's receptor binding domain (RBD) in a translational porcine model for pre-clinical studies. We generated a multiepitope recombinant protein engineered to include six coding conserved epitopes from the RBD domain of the SARS-CoV-2 S protein. Pigs were divided into groups and immunized with different doses of the protein, with serum samples collected over time to determine antibody responses by indirect ELISA and antibody titration. Peptide recognition was also analyzed by Western blotting. A surrogate neutralization assay with recombinant ACE2 and RBDs was performed. Intranasal doses of the immunogen were also prepared and tested on Vietnamese minipigs. When the immunogen was administered subcutaneously, it induced specific IgG antibodies in pigs, and higher doses correlated with higher antibody levels. Antibodies from immunized pigs recognized individual peptides in the multiepitope vaccine and inhibited RBD-ACE2 binding for five variants of concern (VOC). Comparative antigen delivery methods showed that both, subcutaneous and combined subcutaneous/intranasal approaches, induced specific IgG and IgA antibodies, with the subcutaneous approach having superior neutralizing activity. CHIVAX elicited systemic immunity, evidenced by specific IgG antibodies in the serum, and local mucosal immunity, indicated by IgA antibodies in saliva, nasal, and bronchoalveolar lavage secretions. Importantly, these antibodies demonstrated neutralizing activity against SARS-CoV-2 in vitro. The elicited antibodies recognized individual epitopes on the chimeric protein and demonstrated the capacity to block RBD-ACE2 binding of the ancestral SARS-CoV-2 strain and four VOCs. The findings provide proof of concept for using multiepitope recombinant antigens and a combined immunization protocol to induce a neutralizing immune response against SARS-CoV-2 in the pig translational model for preclinical studies.

The pH-responsive zeolitic imidazolate framework nanoparticle as a promising immune-enhancing adjuvant for anti-caries vaccine

ObjectivesStreptococcus mutans (S. mutans) is the main aetiologic bacterium of dental caries, whose protein antigen (PAc) has been administered as an anti-caries vaccine. In addition, several fusion proteins or PAc combined with adjuvants were used as anti-caries vaccines to improve the relatively weak immunogenicity of PAc. However, there are no nanoparticle-based adjuvants with good biocompatibility, excellent biodegradability, or the high loading performance of antigens used for anti-caries vaccines. This study aimed to prepare an innovative nanoparticle-based anti-caries vaccine and evaluate immune responses elicited by this vaccine in vitro and in vivo. MethodsIn this study, an anti-caries vaccine was prepared by an antigen of recombinant protein PAc from S. mutans and an adjuvant of zeolitic imidazolate framework-8 nanoparticles (ZIF-8 NPs) synthesized using a hydrothermal method. Then, mice were administrated intranasally by ZIF-8@PAc vaccine, and immune responses were evaluated. ResultsZIF-8 NPs not only greatly improved the internalization of the antigen but also released the PAc protein after degradation of ZIF-8 NPs in lysosomes for the further processing and presentation of antigen-presenting cells. In addition, ZIF-8@PAc induced significantly more potent PAc-specific serum IgG and saliva IgA antibodies, a higher splenocyte proliferation index, higher levels of the cytokines IL-4, IL-6, IL-10, IL-17A and IFN-γ, and a higher percentage of mature DCs and CD4+ memory T cells in vivo. ConclusionsThe ZIF-8 NPs, as an anti-caries vaccine adjuvant-assisted antigen PAc, elicit significantly potent immune responses, aiding in the further prevention of dental caries. Clinical significanceVaccine immunotherapy is an attractive strategy for prevention and treatment of dental caries. The ZIF-8@PAc vaccine can induce significantly high level of immune responses in this study, which indicates great potential for prevention and treatment of caries.

Prevalence of saliva immunoglobulin A antibodies reactive with severe acute respiratory syndrome coronavirus 2 among Japanese people unexposed to the virus.

While the COVID‐19 pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) poses a threat to public health as the number of cases and COVID‐19‐related deaths are increasing worldwide, the incidence of the virus infection is extremely low in Japan compared with many other countries. To explain this uncommon phenomenon, we investigated the prevalence of naturally occurring (“natural”) antibodies, focusing on those of the secretory immunoglobulin A (sIgA) form, reactive with SARS‐CoV‐2 among Japanese people. One hundred and eighty healthy Japanese volunteers of a wide range of age who had been considered to be unexposed to SARS‐CoV‐2 participated in this study. Saliva samples and blood samples were collected from all of the 180 participants and 139 adults (aged ≥ 20 years) included therein, respectively. The determination of saliva IgA antibodies, mostly comprising sIgA antibodies, as well as serum IgA and immunoglobulin G antibodies, reactive with the receptor binding domain of the SARS‐CoV‐2 spike‐1 subunit proteins was conducted using an enzyme‐linked immunosorbent assay. The major findings were that 52.78% (95% confidence interval, 45.21%–60.25%) of the individuals who had not been exposed to SARS‐CoV‐2 were positive for saliva IgA antibodies with a wide range of levels between 0.002 and 3.272 ng/mL, and that there may be a negative trend in positivity for the antibodies according to age. As we had expected, a frequent occurrence of assumable “natural” sIgA antibodies reactive with SARS‐CoV‐2 among the studied Japanese participant population was observed.

SARS-CoV-2 identification and IgA antibodies in saliva: One sample two tests approach for diagnosis

AimThis study aims to verify whether standardized saliva collection is suitable for SARS-CoV-2 molecular detection and IgA measurement. Methods43 COVID-19 inpatients and 326 screening subjects underwent naso-pharyngeal (NP)-swab and saliva collection (Salivette). Inpatients also underwent repeated blood collections to evaluate inflammation and organs involvement. In all patients and subjects, SARS-CoV-2 (gene E) rRT-PCR was undertaken in saliva and NP-swabs. Salivary IgA and serum IgA, IgG, IgM were measured on inpatients’ samples. ResultsNP-swabs and saliva were both SARS-CoV-2 positive in 7 (16%) or both negative in 35 (82%) out of 43 patients successfully included in the study. NP-swabs and saliva results did not perfectly match in one patient (saliva positive, NP-swab negative). Positive molecular results were significantly associated with disease duration (p = 0.0049). 326/326 screening subjects were SARS-CoV-2 negative on both NP-swabs and saliva. Among the 27 saliva samples tested for IgA, 18 were IgA positive. Salivary IgA positivity was associated with pneumonia (p = 0.002) and CRP values (p = 0.0183), not with other clinical and molecular data, or with serum immunoglubulins. ConclusionsA standardized saliva collection can be adopted to detect SARS-CoV-2 infection in alternative to NP-swabs. Preliminary data on salivary IgA support the use of saliva also for patient monitoring.

Changes in the concentration of anti-Leishmania antibodies in saliva of dogs with clinical leishmaniosis after short-term treatment

The aim of this study was to evaluate the possible changes in the concentration of anti-Leishmania antibodies in saliva samples from dogs with clinical leishmaniosis after short-term treatment. Twenty dogs with clinical signs and laboratory abnormalities compatible with canine leishmaniosis (CanL) were diagnosed and treated with a standard antimonial plus allopurinol therapy. The concentration of anti-Leishmania IgG2 and IgA antibodies in saliva was measured at the time of diagnosis (day 0) and after treatment (day 30) by time-resolved immunofluorometric assays (TR-IFMAs) and results were compared with those of serum. In addition, correlations between antibody concentrations in saliva and serum, clinical scores and selected laboratory analytes were calculated. TR-IFMA results were expressed as Units of Fluorometry for Leishmania (UFL). Most dogs that adequately responded to treatment (n = 17) showed a reduction of anti-Leishmania antibodies in saliva [median IgG2: from 678.0 (day 0) to 201.1 UFL (day 30), p < 0.0001; median IgA: from 91.3 (day 0) to 60.2 UFL (day 30), p < 0.01] in accordance with clinical improvement (p < 0.0001). However, two of these dogs showed an increase of anti-Leishmania antibodies in saliva. Among dogs that did not improve after one month of treatment (n = 3), two showed a reduction in serum and saliva antibodies. In these two dogs, clinical recovery was achieved after one additional month of treatment with allopurinol. The other dog that did not respond to treatment showed increases in the concentration of anti-Leishmania antibodies, both in saliva and serum, and did not adequately respond to an additional month of treatment with allopurinol. From this pilot study, it could be concluded that, despite the low number of dogs used, the measurement of anti-Leishmania IgG2 and IgA antibodies in saliva could have a potential use for treatment monitoring of CanL, provided that a sufficient amount of specific antibodies is present at diagnosis. This is because, especially in the case of IgG2, there is a high correlation between the saliva and serum concentrations, and the reduction of antibodies is generally in accordance with the clinical improvement. Further long-term studies with a larger population should be undertaken to confirm this potential.

Cross-reactive saliva IgA antibodies to oxidized LDL and periodontal pathogens in humans.

Oxidized low-density lipoproteins (oxLDL) are formed as a result of lipid peroxidation and are highly immunogenic and proatherogenic. In this study, saliva antibodies binding to oxLDL, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) were characterized and their cross-reactivity was evaluated. Resting and stimulated saliva samples were collected from 36 healthy adults (mean age 26years). Saliva IgA, IgG and IgM autoantibody levels to copper oxidized LDL (CuOx-LDL) and malondialdehyde acetaldehyde-modified LDL (MAA-LDL) were determined with chemiluminescence immunoassay. Saliva IgA and IgG antibodies binding to MAA-LDL and CuOx-LDL were detected in all samples and they were associated with the saliva levels of IgA and IgG to P.gingivalis and A.actinomycetemcomitans. Competitive immunoassay showed that saliva antibodies to MAA-LDL cross-reacted specifically with P.gingivalis. The autoantibody levels to oxLDL in saliva were not associated with the autoantibody levels to oxLDL in plasma or with saliva apolipoprotein B 100 levels. Saliva contains IgA and IgG binding to oxLDL, which showed cross-reactive properties with the periodontal pathogens Porphyromonas gingivalis (P.g). The data suggest that secretory IgA to P.g may participate in immune reactions involved in LDL oxidation through molecular mimicry.

Quantification of anti-Leishmania antibodies in saliva of dogs

Detection of serum anti-Leishmania antibodies by quantitative or qualitative techniques has been the most used method to diagnose Canine Leishmaniosis (CanL). Nevertheless, saliva may represent an alternative to blood because it is easy to collect, painless and non-invasive in comparison with serum. In this study, two time-resolved immunofluorometric assays (TR-IFMAs) for quantification of anti-Leishmania IgG2 and IgA antibodies in saliva were developed and validated and their ability to distinguish Leishmania-seronegative from seropositive dogs was evaluated. The analytical study was performed by evaluation of assay precision, sensitivity and accuracy. In addition, serum from 48 dogs (21 Leishmania-seropositive and 27 Leishmania-seronegative) were analyzed by TR-IFMAs. The assays were precise, with an intra- and inter-assay coefficients of variation lower than 11%, and showed high level of accuracy, as determined by linearity under dilution (R2=0.99) and recovery tests (>88.60%). Anti-Leishmania IgG2 antibodies in saliva were significantly higher in the seropositive group compared with the seronegative (p<0.0001), whereas no significant differences for anti-Leishmania IgA antibodies between both groups were observed. Furthermore, TR-IFMA for quantification of anti-Leishmania IgG2 antibodies in saliva showed higher differences between seropositive and seronegative dogs than the commercial assay used in serum. In conclusion, TR-IFMAs developed may be used to quantify anti-Leishmania IgG2 and IgA antibodies in canine saliva with an adequate precision, analytical sensitivity and accuracy. Quantification of anti-Leishmania IgG2 antibodies in saliva could be potentially used to evaluate the humoral response in CanL. However, IgA in saliva seemed not to have diagnostic value for this disease. For future studies, it would be desirable to evaluate the ability of the IgG2 assay to detect dogs with subclinical disease or with low antibody titers in serum and also to study the antibodies behaviour in saliva during the treatment of CanL.

Immune responses induced in rabbits after oral administration of bovine serum albumin in combination with different adjuvants (herb extracts, aluminium hydroxide and platinum nanoparticles)

&lt;p&gt;The aim of the current study was to evaluate the immunostimulatory activity of 10 different herbal extracts from &lt;em&gt;Vitex agnus-castus&lt;/em&gt;, &lt;em&gt;Vinca major, Aloe arborescens &lt;/em&gt;and the polyherbal product containing extracts from &lt;em&gt;Sambucus nigra&lt;/em&gt;, &lt;em&gt;Primula&lt;/em&gt;&lt;em&gt; versis&lt;/em&gt;, &lt;em&gt;Pinus alba&lt;/em&gt;, &lt;em&gt;Gentiana lutea&lt;/em&gt;, &lt;em&gt;Cetraria islandica&lt;/em&gt;, &lt;em&gt;Eucaliptus globulus&lt;/em&gt;, &lt;em&gt;Citrus limon &lt;/em&gt;and aluminium hydroxide, as well as platinum nanoparticles. Rabbits were immunized three times orally with bovine serum albumin (BSA) in combination with the components mentioned above. BSA-specific IgA antibodies in saliva and IgG antibodies in serum were examined by ELISA. It was found that the rabbits immunized with BSA in combination with either platinum nanoparticles or aluminium hydroxide had higher titres of BSA-specific IgA antibodies in their saliva at day 56 of observation. Likewise, rabbits treated with BSA and &lt;em&gt;Vinca major &lt;/em&gt;or &lt;em&gt;Aloe arborescens &lt;/em&gt;extracts showed higher levels of BSA-specific IgG antibodies in the serum at the end of observation. These results suggest that some plant extracts, aluminium hydroxide and platinum nanoparticles components could be used as oral adjuvants or as immunomodulators for rabbits.&lt;/p&gt;

Salivary and Serum Antibody Response Against Neisseria meningitidis After Vaccination With Conjugate Polysaccharide Vaccines in Ethiopian Volunteers.

Meningococcal conjugate vaccines induce serum antibodies crucial for protection against invasive disease. Salivary antibodies are believed to be important for hindering meningococcal acquisition and/or clearance of established carriage. In this study, we measured salivary IgA and IgG antibodies induced by vaccination with a monovalent serogroup A conjugate vaccine or a tetravalent A, C, W and Y conjugate vaccine, in comparison with antibody levels in serum. Saliva and serum samples from Ethiopian volunteers (1-29years) collected before and eight times on a weekly basis after receiving the serogroup A conjugate vaccine, the tetravalent serogroup A, C, W and Y conjugate vaccine, or no vaccine (control group), were analysed using a multiplex microsphere immunoassay for antibody detection. Serogroup-specific IgG antibody levels in saliva increased significantly after vaccination with both vaccines. The monovalent serogroup A vaccine also induced an increase in salivary IgA antibodies. A strong correlation between serogroup-specific IgG antibodies in saliva and serum, and a somewhat lower correlation for IgA, was observed for all serogroups. There was also a strong correlation between specific secretory IgA and IgA antibodies in saliva for all serogroups. Meningococcal conjugate vaccines are able to elicit salivary antibodies against serogroup A, C, W and Y correlating with antibody levels in serum. The strong correlation between saliva and serum antibody levels indicates that saliva may be used as a surrogate of systemic antibody responses.

Genetic and phenotypic relationships between carbohydrate larval antigen (CarLA) IgA, parasite resistance and productivity in serial samples taken from lambs after weaning

Genetic selection for enhanced levels of protective antibody to specific nematode antigens may be a more user-friendly means of selecting animals for resistance to gastrointestinal nematodes than obtaining faecal samples and selecting on the basis of faecal egg counts. Saliva IgA antibody levels to the L3-specific surface glycan known as carbohydrate larval antigen were measured on six occasions over a 5month period in approximately 350 lambs. The carbohydrate larval antigen IgA response increased markedly with time as the lambs grazed on pasture naturally contaminated with nematode parasite larvae. The monthly loge transformed carbohydrate larval antigen IgA levels were moderately heritable at all samplings, with a combined value of 0.28±0.10 and a repeatability of 0.35±0.03. The genetic correlations between all samplings were high (0.86), suggesting that testing for a carbohydrate larval antigen IgA response could be carried out at any time in the 5months post-weaning. The transformed carbohydrate larval antigen IgA levels were genetically and phenotypically correlated negatively with loge transformed (faecal egg count+50), averaging −0.57±0.20 and −0.12±0.03 (P<0.05), respectively. The correlations between carbohydrate larval antigen IgA and breech-soiling (dag score) never reached significance. However, genetic correlations between carbohydrate larval antigen IgA and live weight were always positive and significantly so, especially at the beginning and end of the trial, indicating that carbohydrate larval antigen IgA production may be an important genetic determinant of growth rate for lambs experiencing a larval challenge. The data suggest that the ideal time to sample for a carbohydrate larval antigen IgA response and maximise selection for lowered faecal egg count and increased live-weight would be in the first 2months after weaning.

125* Comparison of real time diagnostic chemistries to detect early and chronic Pseudomonas aeruginosa colonisation in cystic fibrosis patients

124 Saliva IgA antibodies is a diagnostic tool for sinusitis caused by Pseudomonas aeruginosa in patients with cystic fibrosis K. Aanaes1, H.K. Johansen2, S.S. Poulsen3, T. Pressler4, C. Buchwald1, N. Hoiby2. 1Department of Otolaryngology − Head & Neck Surgery, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 2Department of Clinical Microbiology 9301, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 3Endocrinology Research Section, Department of Biomedical Sciences, The Faculty of Health Sciences, The Univerity of Copenhagen, Copenhagen, Denmark; 4Copenhagen CF Centre, Pediatric Pulmonary Service, Department of Pediatrics, Rigshospitalet, Copenhagen, Denmark

124 Saliva IgA antibodies is a diagnostic tool for sinusitis caused by Pseudomonas aeruginosa in patients with cystic fibrosis

124 Saliva IgA antibodies is a diagnostic tool for sinusitis caused by Pseudomonas aeruginosa in patients with cystic fibrosis

Protective Immunity to Streptococcus sobrinus Induced by Nasal Immunization with Surface Protein Antigen

In this study, mice were immunized nasally with surface protein antigen A (SpaA) of Streptococcus sobrinus and cholera toxin, as a mucosal adjuvant. Immunization of mice with SpaA plus cholera toxin elicited significant levels of SpaA-specific IgG and IgA in serum, and mucosal IgA antibodies in saliva. Antibody-forming cell analysis confirmed the antibody titers by detecting high numbers of SpaA-specific antibody-forming cells in spleen and salivary glands. Furthermore, CD4+ T cells from spleen and cervical lymph nodes exhibited significant proliferative responses when restimulated with SpaA in vitro. Importantly, mice that were nasally immunized with SpaA plus cholera toxin exhibited significantly reduced oral colonization by S. sobrinus. These results show that nasal administration of SpaA is potentially an effective nasal vaccine against dental caries and reduces the colonization of S. sobrinus in the oral cavity.

Oral immunization with Porphyromonas gingivalis outer membrane protein and CpG oligodeoxynucleotides elicits T helper 1 and 2 cytokines for enhanced protective immunity

The aim of this study was to evaluate the efficacy of an oral vaccine containing the 40-kDa outer membrane protein of Porphyromonas gingivalis (40K OMP) and synthetic oligodeoxynucleotides containing unmethylated CpG dinucleotides (CpG ODN) to control oral infection by P. gingivalis. [run on]40K-OMP40K-OMP40K-OMPOral immunization with 40K-OMP plus CpG ODN induced significant 40K-OMP-specific serum IgG, IgA and saliva IgA antibody responses. The 40K-OMP-specific CD4(+) T cells induced by oral 40K-OMP plus CpG ODN produced both Th1 (IFN-gamma) and Th2 (IL-4) cytokines. Furthermore, increased frequencies of CD11c(+)B220(+) DCs and CD11c(+)CD11b(+) DCs with up-regulated expression of CD80, CD86, CD40 and MHC II molecules were noted in spleen, Peyer's patches and cervical lymph nodes. Immunized mice were then infected orally with P. gingivalis to determine whether the immune responses induced by oral 40K-OMP plus CpG ODN were capable of suppressing bone resorption caused by P. gingivalis infection. Mice given 40K-OMP plus CpG ODN showed significantly reduced bone loss associated with oral infection by P. gingivalis.Thus, oral administration of 40K-OMP together with CpG ODN induces Th1- and Th2-type cells, which provide help for protective immunity against P. gingivalis infection. This may be an important tool for prevention of chronic periodontitis.

Nasal Administration of Glucosyltransferase-I of Streptococcus Sobrinus without Adjuvant Induces Protective Immunity

This study seeks to assess the efficacy of the glucosyltransferase-I (GTF-I) produced by Streptococcus sobrinus as a nasal vaccine for the prevention of dental caries. Nasal immunization of mice with GTF-I elicited significant levels of GTF-I-specific IgG and IgA in serum and mucosal IgA antibodies in saliva. Antibody-forming cell analysis confirmed the antibody titers by detecting high numbers of GTF-I-specific antibody-forming cells in spleen and salivary glands. Coadministration of GTF-I and oligodeoxynucleotides (ODN) containing unmethylated cytosine-phosphate-guanine (CpG) dinucleotides (CpG ODN) as adjuvant further elevated salivary IgA antibody responses; however, the increase in serum antibody levels was slight. GTF-I-specific IgG antibodies from mice given GTF-I alone or GTF-I plus CpG ODN inhibited biofilm formation by S. sobrinus. Finally, the mice given nasal GTF-I showed protection and significant inhibition of dental caries caused by oral infection with S. sobrinus even without the use of CpG ODN. These results suggest that nasal administration of GTF-I could be an important tool for the prevention of dental caries.

Immunogenicity and Protective Efficacy of Heat-Killed Recombinant Lactobacillus casei Expressing Outer Membrane Protein of Porphyromonas gingivalis

This study seeks to access the potential of a heat-killed recombinant Lactobacillus casei expressing 40-kDa outer membrane protein of Porphyromonas gingivalis (L. casei/40k-OMP) as a nasal vaccine against P. gingivalis infection. The 40-kDa outer membrane protein of P. gingivalis (40k-OMP) were expressed on the surface of L. casei using poly-γ-glutamate symthetase A (pgsA). Nasal immunization with heat-killed L. casei/40k-OMP induced significant 40k-OMP-specific serum IgG, IgA and saliva IgA antibody responses. Antibody-forming cell analysis revealed high numbers of 40k-OMP-specific IgA antibody-forming cells in the submandibular glands of mice given heat-killed L. casei/40k-OMP. Importantly, nasal administration of heat-killed L. casei/40k-OMP resulted in the significant reduction of alveolar bone loss caused by oral infection with P. gingivalis. Because L. casei is one of major probiotic bacterias, nasal administration of heat-killed L. casei/40k-OMP should be an effective and safe mucosal vaccine for humans against P. gingivalis infection and may be an important tool for prevention of chronic periodontitis.

Nasal Immunization with Porphyromonas gingivalis Outer Membrane Protein Decreases P. gingivalis -Induced Atherosclerosis and Inflammation in Spontaneously Hyperlipidemic Mice

Porphyromonas gingivalis has been shown to accelerate atherosclerotic lesion development in hyperlipidemic animals. We assessed the potential of a nasal vaccine against P. gingivalis infection for the prevention of atherosclerosis. Apolipoprotein E-deficient spontaneously hyperlipidemic (Apoe(shl)) mice were nasally immunized with the 40-kDa outer membrane protein (OMP) of P. gingivalis plus cholera toxin (CT) as adjuvant and then challenged intravenously with P. gingivalis strain 381. The animals were euthanized 11 or 14 weeks later. Atheromatous lesions in the proximal aorta of each animal were analyzed histomorphometrically, and the serum concentrations of 40-kDa OMP-specific antibodies and cytokines were determined. The areas of the aortic sinus that were covered with atherosclerotic plaque and the serum levels of inflammatory cytokines and chemokines were increased in Apoe(shl) mice challenged with P. gingivalis compared to nonchallenged mice. In comparison, nasal immunization with 40-kDa OMP plus CT significantly reduced atherosclerotic plaque accumulation in the aortic sinus and lowered the serum levels of cytokines and chemokines compared to nonimmunized animals. Nasal immunization also induced 40-kDa OMP-specific serum immunoglobulin G (IgG) and saliva IgA antibody responses. These findings suggest that systemic infection with P. gingivalis accelerates atherosclerosis in Apoe(shl) mice, and 40-kDa OMP plus CT may be an effective nasal vaccine for the reduction of atherosclerosis accelerated by P. gingivalis in the hyperlipidemic mouse model.

Implications of Oral Helicobacter pylori for the Outcome of its Gastric Eradication Therapy

Helicobacter pylori (H. pylori) is an important pathogen in gastritis, peptic ulcer and possibly gastric cancer, but several questions remain unanswered. Particularly how the organism is transmitted and what is the relationship between oral presence of H. pylori and the gastric infection. Accordingly, we aimed to characterize the H. pylori in oral cavity and to evaluate its relationship to gastric H. pylori infection. Out of total 100 screened for H. pylori infection female subjects (40 to 85 y), 49 patients (pts), who had positive C-urea breath test (UBT) and dyspeptic symptoms, agreed for 1 week regimen of triple anti-H. pylori therapy. The presence of H. pylori in oral cavity was assessed using bacterial culture from saliva and gingival pockets. Gastric H. pylori infection was estimated using capsulated C-urea breath test and plasma anti-H. pylori IgG and saliva IgA antibodies. In addition, plasma gastrin, ghrelin, and pepsinogen I were measured by radioimmunoassay. In selected patients, gastroscopy was additionally performed and gastric biopsy samples were taken for H. pylori random amplification of polymorphic DNA genetic profiling. The triple therapy resulted in gastric H. pylori eradication in 79% pts, along with significant decrease of plasma gastrin combined with an increase in plasma ghrelin and pepsinogen I (PgI) levels and a marked alleviation of dyspeptic symptoms. In contrast to gastric effects, the eradication therapy failed to cause any changes in the presence of H. pylori in oral cavity. Moreover no relationship was observed between the presence of H. pylori in oral cavity and the gastric H. pylori eradication. In line with these findings, no relationship between gastric and oral H. pylori was found using genetic profiling by random amplification of polymorphic DNA. H. pylori was detected both in the oral cavity and the stomach but oral H. pylori had no relation to gastric H. pylori and remained unaffected by eradication of gastric H. pylori.

Oral transmission of HIV, reality or fiction? An update

Human immunodeficiency virus (HIV) and many other viruses can be isolated in blood and body fluids, including saliva, and can be transmitted by genital-genital and especially anal-genital sexual activity. The risk of transmission of HIV via oral sexual practices is very low. Unlike other mucosal areas of the body, the oral cavity appears to be an extremely uncommon transmission route for HIV. We present a review of available evidence on the oral-genital transmission of HIV and analyse the factors that act to protect oral tissues from infection, thereby reducing the risk of HIV transmission by oral sex. Among these factors we highlight the levels of HIV RNA in saliva, presence of fewer CD4+ target cells, presence of IgA antibodies in saliva, presence of other infections in the oral cavity and the endogenous salivary antiviral factors lysozyme, defensins, thrombospondin and secretory leucocyte protease inhibitor (SLPI).