scholarly journals Antibody in Lymphocyte Supernatant (ALS) responses after oral vaccination with live Shigella sonnei vaccine candidates WRSs2 and WRSs3 and correlation with serum antibodies, ASCs, fecal IgA and shedding

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0259361
Author(s):  
Malabi M. Venkatesan ◽  
Cassandra Ballou ◽  
Shoshana Barnoy ◽  
Monica McNeal ◽  
Jill El-Khorazaty ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Oral Vaccine ◽  
Serum Antibody ◽  
Vaccine Dose ◽  
Dependent Manner ◽  
Serum Antibodies ◽  
Oral Vaccination ◽  
Vaccine Candidates ◽  
Mucosal Immune Responses

The levels of antigen-specific Antibodies in Lymphocyte Supernatant (ALS) using an ELISA are being used to evaluate mucosal immune responses as an alternate to measuring the number of Antibody Secreting Cells (ASCs) using an ELISpot assay. A recently completed trial of two novel S. sonnei live oral vaccine candidates WRSs2 and WRSs3 established that both candidates were safe, well tolerated and immunogenic in a vaccine dose-dependent manner. Previously, mucosal immune responses were measured by assaying IgA- and IgG-ASC in peripheral blood mononuclear cells (PBMCs). In this report, the magnitude of the S. sonnei antigen-specific IgA- and IgG-ALS responses was measured and correlated with previously described ASCs, serum antibodies, fecal IgA and vaccine shedding. Overall, the magnitude of S. sonnei anti-Invaplex50 ALS was higher than that of LPS or IpaB, and both vaccines demonstrated a more robust IgA-ALS response than IgG; however, compared to WRSs3, the magnitude and percentage of responders were higher among WRSs2 recipients for IgA- or IgG-ALS. All WRSs2 vaccinees at the two highest doses responded for LPS and Invaplex50-specific IgA-ALS and 63–100% for WRSs3 vaccinees responded. Regardless of the vaccine candidate, vaccine dose or detecting antigen, the kinetics of ALS responses were similar peaking on days 7 to 9 and returning to baseline by day 14. The ALS responses were vaccine-specific since no responses were detected among placebo recipients at any time. A strong correlation and agreement between responders/non-responders were noted between ALS and other mucosal (ASC and fecal IgA) and systemic (serum antibody) immune responses. These data indicate that the ALS assay can be a useful tool to evaluate mucosal responses to oral vaccination, an observation noted with trials of other bacterial diarrheal pathogens. Furthermore, this data will guide the list of immunological assays to be conducted for efficacy trials in different populations. It is hoped that an antigen-specific-ALS titer may be a key mucosal correlate of protection, a feature not currently available for any Shigella vaccines candidates. https://clinicaltrials.gov/show/NCT01336699.

scholarly journals Oral Vaccination of Grass Carp (Ctenopharyngodon idella) with Baculovirus-Expressed Grass Carp Reovirus (GCRV) Proteins Induces Protective Immunity against GCRV Infection

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 41
Author(s):  
Changyong Mu ◽  
Qiwang Zhong ◽  
Yan Meng ◽  
Yong Zhou ◽  
Nan Jiang ◽  
...  
Keyword(s):  
Survival Rate ◽  
Grass Carp ◽  
Oral Vaccine ◽  
Serum Antibody ◽  
Ctenopharyngodon Idella ◽  
Control Group ◽  
Oral Vaccination ◽  
Grass Carp Reovirus ◽  
Silkworm Pupae ◽  
Grass Carp Ctenopharyngodon Idella

The grass carp reovirus (GCRV) causes severe hemorrhagic disease with high mortality and leads to serious economic losses in the grass carp (Ctenopharyngodon idella) industry in China. Oral vaccine has been proven to be an effective method to provide protection against fish viruses. In this study, a recombinant baculovirus BmNPV-VP35-VP4 was generated to express VP35 and VP4 proteins from GCRV type Ⅱ via Bac-to-Bac baculovirus expression system. The expression of recombinant VP35-VP4 protein (rVP35-VP4) in Bombyx mori embryo cells (BmE) and silkworm pupae was confirmed by Western blotting and immunofluorescence assay (IFA) after infection with BmNPV-VP35-VP4. To vaccinate the grass carp by oral route, the silkworm pupae expressing the rVP35-VP4 proteins were converted into a powder after freeze-drying, added to artificial feed at 5% and fed to grass carp (18 ± 1.5 g) for six weeks, and the immune response and protective efficacy in grass carp after oral vaccination trial was thoroughly investigated. This included blood cell counting and classification, serum antibody titer detection, immune-related gene expression and the relative percent survival rate in immunized grass carp. The results of blood cell counts show that the number of white blood cells in the peripheral blood of immunized grass carp increased significantly from 14 to 28 days post-immunization (dpi). The differential leukocyte count of neutrophils and monocytes were significantly higher than those in the control group at 14 dpi. Additionally, the number of lymphocytes increased significantly and reached a peak at 28 dpi. The serum antibody levels were significantly increased at Day 14 and continued until 42 days post-vaccination. The mRNA expression levels of immune-related genes (IFN-1, TLR22, IL-1β, MHC I, Mx and IgM) were significantly upregulated in liver, spleen, kidney and hindgut after immunization. Four weeks post-immunization, fish were challenged with virulent GCRV by intraperitoneal injection. The results of this challenge study show that orally immunized group exhibited a survival rate of 60% and relative percent survival (RPS) of 56%, whereas the control group had a survival rate of 13% and RPS of 4%. Taken together, our results demonstrate that the silkworm pupae powder containing baculovirus-expressed VP35-VP4 proteins could induce both non-specific and specific immune responses and protect grass carp against GCRV infection, suggesting it could be used as an oral vaccine.

scholarly journals Tonsils of the Soft Palate Do Not Mediate the Response of Pigs to Oral Vaccination with Heat-Inactivated Mycobacterium bovis

2014 ◽  
Vol 21 (8) ◽  
pp. 1128-1136 ◽  
Author(s):  
Beatriz Beltrán-Beck ◽  
Beatriz Romero ◽  
Mariana Boadella ◽  
Carmen Casal ◽  
Javier Bezos ◽  
...  
Keyword(s):  
Wild Boar ◽  
Mycobacterium Bovis ◽  
Mononuclear Cells ◽  
Mammalian Species ◽  
Serum Antibody ◽  
Control Group ◽  
Mrna Levels ◽  
Oral Vaccination ◽  
Peripheral Blood Mononuclear ◽  
Content Type

ABSTRACTMycobacterium boviscauses animal tuberculosis (TB) in cattle, humans, and other mammalian species, including pigs. The goal of this study was to experimentally assess the responses of pigs with and without a history of tonsillectomy to oral vaccination with heat-inactivatedM. bovisand challenge with a virulentM. bovisfield strain, to compare pig and wild boar responses using the same vaccination model as previously used in the Eurasian wild boar (Sus scrofa), to evaluate the use of several enzyme-linked immunosorbent assays (ELISAs) and lateral flow tests forin vivoTB diagnosis in pigs, and to verify if these tests are influenced by oral vaccination with inactivatedM. bovis. At necropsy, the lesion and culture scores were 20% to 43% higher in the controls than those in the vaccinated pigs. MassiveM. bovisgrowth from thoracic tissue samples was observed in 4 out of 9 controls but in none of the 10 vaccinated pigs. No effect of the presence or absence of tonsils was observed on these scores, suggesting that tonsils are not involved in the protective response to this vaccine in pigs. The serum antibody levels increased significantly only after challenge. At necropsy, the estimated sensitivities of the ELISAs and dual path platform (DPP) assays ranged from 89% to 94%. In the oral mucosa, no differences in gene expression were observed in the control group between the pigs with and without tonsils. In the vaccinated group, the mRNA levels for chemokine (C-C motif) receptor 7 (CCR7), interferon beta (IFN-β), and methylmalonyl coenzyme A mutase (MUT) were higher in pigs with tonsils. Complement component 3 mRNA levels in peripheral blood mononuclear cells (PBMC) increased with vaccination and decreased afterM. bovischallenge. This information is relevant for pig production in regions that are endemic forM. bovisand for TB vaccine research.

scholarly journals A Single Dose of Oral BCG Moreau Fails to Boost Systemic IFN-γResponses to Tuberculin in Children in the Rural Tropics: Evidence for a Barrier to Mucosal Immunization

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Maritza Vaca ◽  
Ana-Lucia Moncayo ◽  
Catherine A. Cosgrove ◽  
Martha E. Chico ◽  
Luiz R. Castello-Branco ◽  
...  
Keyword(s):  
Rural Communities ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Study Groups ◽  
Mucosal Immunization ◽  
Oral Vaccines ◽  
Oral Vaccination ◽  
Peripheral Blood Mononuclear ◽  
Before And After

Immune responses to oral vaccines are impaired in populations living in conditions of poverty in developing countries, and there is evidence that concurrent geohelminth infections may contribute to this effect. We vaccinated 48 children living in rural communities in Ecuador with a single oral dose of 100 mg of BCG Moreau RDJ and measured the frequencies of tuberculin-stimulated peripheral blood mononuclear cells expressing IFN-γbefore and after vaccination. Vaccinated children had active ascariasis(n=20)or had been infected but received short-(n=13)or long-term(n=15)repeated treatments with albendazole prior to vaccination to treat ascariasis. All children had a BCG scar from neonatal vaccination. There was no evidence of a boosting of postvaccination IFN-γresponses in any of the 3 study groups. Our data provide support for the presence of a barrier to oral vaccination among children from the rural tropics that appeared to be independent of concurrent ascariasis.

scholarly journals Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals

2021 ◽  
Author(s):  
Marie I. Samanovic ◽  
Amber R. Cornelius ◽  
Sophie L. Gray-Gaillard ◽  
Joseph Richard Allen ◽  
Trishala Karmacharya ◽  
...  
Keyword(s):  
Immune Responses ◽  
Protective Efficacy ◽  
Vaccine Dose ◽  
Prior History ◽  
Vaccine Candidates ◽  
Antibody Secreting Cell ◽  
Cell Responses ◽  
Efficacy Trials ◽  
History Of ◽  
Humoral Responses

ABSTRACTThe use of COVID-19 vaccines will play a major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccine candidates have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccine candidates differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 13 adults who recovered from COVID-19, compared to 19 adults who did not have prior COVID-19 diagnosis. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8 T cell responses in both cohorts. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but muted responses to the second dose of the vaccine for the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have significant implications for personalizing mRNA vaccination regimens used to prevent COVID-19.One Sentence SummaryPrior history of COVID-19 affects adaptive immune responses to mRNA vaccination.

Depletion of the CD1d-Restricted NKT Cells Suppresses In Vitro Alloreactivity: A Possible Means To Prevent aGVHD.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3069-3069
Author(s):  
S. Patterson ◽  
I. Kotsianidis ◽  
A. Almeida ◽  
M. Politou ◽  
R. David ◽  
...  
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Mononuclear Cells ◽  
Nkt Cells ◽  
Cell Depletion ◽  
Dependent Manner ◽  
Nkt Cell ◽  
Accurate Identification ◽  
Enhancing Effect

Abstract NKT cells constitute a small (<0.1% of blood and marrow T cells) but potent subset of regulatory T cells. Upon engagement of their unique TCR by the glycolipid presenting, MHC-like, non-polymorphic molecule CD1d, they are activated and secrete copious amounts of TH1 and TH2 cytokines. Activated NKT have a pivotal role in modulating all aspects of the innate and adaptive immune responses mainly through their interaction with antigen presenting cells (APC). Mice deficient in NKT or CD1d have diminished TH1 responses against a variety of pathogens and tumours. Conversely, administration of the model glycolipid α-galactosylceramide (αGC) to wild type mice considerably enhances TH1 immune responses in an NKT- and CD1d-dependent manner. In this work we sought to study the in situ role of NKT in alloreactivity. For this purpose, allogeneic mixed lymphocyte reactions (MLR) were performed using 3H incorporation assays. Purified, negatively selected CD3+ cells and irradiated allogeneic peripheral blood mononuclear cells from normal individuals were used as responders and stimulators respectively. After rigorous NKT cell (as identified by staining with the anti-TCRVα24 and -Vβ11 mAbs specific to the NKT TCR α and β chains) depletion by flow sorting we compared MLR reactivity in the presence and absence of NKT. In a series of MLR that included a panel of 4 different responders and 3–5 stimulators, depletion of NKT profoundly suppressed the proliferation by 68.5%±16.9 compared to baseline (i.e., NKT-replete MLR). This suppressive effect was mirrored by a reduction (45.3%±8) of IFNγ secretion in the supernatants of the NKT-depleted MLR compared to baseline. IL-4, IL-10 and TGFβ were not detected in either NKT replete or NKT depleted MLR. When freshly flow-sorted NKT cells were placed against the allogeneic stimulators they did not proliferate indicating that the decrease in the proliferation after NKT cell depletion is due to a decrease in the proliferation of the alloreactive T cells. Taken together, these findings indicate that NKT cells positively regulate the alloresponse, a TH1-driven immune response. Consistent with this, in MLR performed in the presence of αGC (100ng/ml), proliferation was significantly enhanced as compared to baseline MLR (i.e., performed in the presence of the αGC diluent). In a panel of 5 responders against a panel of 3–5 stimulators treatment of the MLR with αGC resulted in a 43.2%±15.2 increase in proliferation. In accordance with the proliferation data, IGNγ production was significantly increased (mean of 53%), whereas IL-4 was undetectable under both conditions. Furthermore, the enhancing effect of αGC was NKT-dependent, as in NKT-depleted MLR proliferation was equally suppressed in the presence of αGC and its diluent (82.6±6.8 vs 82±8.5 respectively, n=3).In summary, we have demonstrated that NKT cells exert an enhancing effect on the alloreactive response and NKT cell depletion effectively suppresses in vitro alloreactivity. These findings set the scene for exploring on one hand the potential for reducing the risk of severe aGVHD by using NKT depletion in allogeneic haemopoietic stem cell transplantation and on the other hand for exploring the adoptive transfer of purified NKT cells to improve immune reconstitution post transplant. In either case, the rapid, accurate identification and physical isolation of the NKT cells is possible either with the use of mAbs highly specific for the TCR of the NKT cells or with the use of the CD1d/α GC tetramer.

scholarly journals Mucosal immune responses induced by oral administration recombinant Bacillus subtilis expressing the COE antigen of PEDV in newborn piglets

2019 ◽  
Vol 39 (3) ◽  
Author(s):  
Jialu Wang ◽  
Lulu Huang ◽  
Chunxiao Mou ◽  
En Zhang ◽  
Yongheng Wang ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Immune Responses ◽  
Oral Administration ◽  
Oral Vaccine ◽  
Oral Immunization ◽  
Economic Losses ◽  
Antigen Delivery ◽  
Newborn Piglets ◽  
Mucosal Immune Responses ◽  
Recombinant Bacillus Subtilis

Abstract Porcine epidemic diarrhea (PED) is a highly contagious disease in newborn piglets and causes substantial economic losses in the world. PED virus (PEDV) spreads by fecal–oral contact and can be prevented by oral immunization. Therefore, it is necessary to develop an effective oral vaccine against PEDV infection. Currently, Bacillus subtilis as recombinant vaccine carrier has been used for antigen delivery and proved well in immune effect and safety. The present study evaluated the immunogenicity of recombinant Bacillus subtilis (B. subtilis-RC) in piglets via oral administration. After oral immunization in piglets, B. subtilis-RC significantly increased the local mucosal immune responses. Oral administration with B. subtilis-RC significantly improved the level of specific mucosal immunoglobulin A (IgA) antibodies against PEDV infection, through enlarging the area of Peyer’s patches (PPs) and increasing the number of ileum IgA+ secreting (SIgA) cells. In the meantime, B. subtilis-RC remarkably increased the number of intraepithelial lymphocytes (IELs). We also observed that oral administration of B. subtilis-RC significantly increased CD3+T lymphocytes’ numbers and up-regulated the ratio of CD4+/CD8+ T cells. Furthermore, high titers of specific serum immunoglobulin G (IgG) revealed satisfactory systemic immune response against PEDV infection. In summary, our study demonstrated that oral administration of B. subtilis-RC could trigger a high level of local and systemic immune responses and would be a promising candidate vaccine against PEDV infection in piglets.

scholarly journals Induction of PrPSc-specific systemic and mucosal immune responses in white-tailed deer with an oral vaccine for chronic wasting disease

Prion ◽  
2017 ◽  
Vol 11 (5) ◽  
pp. 368-380 ◽  
Author(s):  
Ryan Taschuk ◽  
Erin Scruten ◽  
Murray Woodbury ◽  
Neil Cashman ◽  
Andrew Potter ◽  
...  
Keyword(s):  
Immune Responses ◽  
Chronic Wasting Disease ◽  
Oral Vaccine ◽  
Wasting Disease ◽  
Mucosal Immune Responses

scholarly journals Application of an M-cell-targeting ligand for oral vaccination induces efficient systemic and mucosal immune responses against a viral antigen

2013 ◽  
Vol 25 (11) ◽  
pp. 623-632 ◽  
Author(s):  
Sae-Hae Kim ◽  
Dae-Im Jung ◽  
In-Young Yang ◽  
Sun-Hee Jang ◽  
Ju Kim ◽  
...  
Keyword(s):  
Immune Responses ◽  
Viral Antigen ◽  
Cell Targeting ◽  
M Cell ◽  
Oral Vaccination ◽  
Mucosal Immune Responses

scholarly journals Pilot Study of phoP/phoQ-DeletedSalmonella enterica Serovar Typhimurium ExpressingHelicobacter pylori Urease in Adult Volunteers

2000 ◽  
Vol 68 (4) ◽  
pp. 2135-2141 ◽  
Author(s):  
Haroula Angelakopoulos ◽  
Elizabeth L. Hohmann
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Oral Vaccine ◽  
Multicopy Plasmid ◽  
Serovar Typhimurium ◽  
Specific Factors ◽  
Adult Volunteers ◽  
Heterologous Antigens ◽  
Previous Clinical Study

ABSTRACT Attenuated Salmonella enterica serovar Typhi has been studied as an oral vaccine vector. Despite success with attenuatedS. enterica serovar Typhimurium vectors in animals, early clinical trials of S. enterica serovar Typhi expressing heterologous antigens have shown that few subjects have detectable immune responses to vectored antigens. A previous clinical study ofphoP/phoQ-deleted S. enterica serovar Typhi expressing Helicobacter pylori urease from a multicopy plasmid showed that none of eight subjects had detectable immune responses to the vectored antigen. In an attempt to further define the variables important for engendering immune responses to vectored antigens in humans, six volunteers were inoculated with 5 × 107 to 8 × 107 CFU ofphoP/phoQ-deleted S. enterica serovar Typhimurium expressing the same antigen. Two of the six volunteers had fever; none had diarrhea, bacteremia, or other serious side effects. The volunteers were more durably colonized than in previous studies ofphoP/phoQ-deleted S. enterica serovar Typhi. Five of the six volunteers seroconverted to S. entericaserovar Typhimurium antigens and had strong evidence of anti-Salmonella mucosal immune responses by enzyme-linked immunospot studies. Three of six (three of five who seroconverted toSalmonella) had immune responses in the most sensitive assay of urease-specific immunoglobulin production by blood mononuclear cells in vitro. One of these had a fourfold or greater increase in end-point immunoglobulin titer in serum versus urease. AttenuatedS. enterica serovar Typhimurium appears to be more effective than S. enterica serovar Typhi for engendering immune responses to urease. Data suggest that this may be related to a greater stability of antigen-expressing plasmid in S. enterica serovar Typhimurium and/or prolonged intestinal colonization. Specific factors unique to nontyphoidal salmonellae may also be important for stimulation of the gastrointestinal immune system.

scholarly journals Local Secretory Immunoglobulin A and Postimmunization Gastritis Correlate with Protection against Helicobacter pylori Infection after Oral Vaccination of Mice

1999 ◽  
Vol 67 (5) ◽  
pp. 2531-2539 ◽  
Author(s):  
Takayuki Goto ◽  
Akira Nishizono ◽  
Toshio Fujioka ◽  
Junko Ikewaki ◽  
Kumato Mifune ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Mononuclear Cells ◽  
Immunoglobulin A ◽  
Vaccine Dose ◽  
Interleukin 4 ◽  
Secretory Iga ◽  
Dependent Manner ◽  
Iga Antibody ◽  
H Pylori ◽  
Dose Dependent

ABSTRACT C57BL/6 mice were orally immunized with five weekly doses of 2 mg, 200 μg, or 2 μg of Helicobacter pylori (Sydney strain) whole-cell sonicate combined with cholera toxin. One week after the last vaccination, mice were challenged with 5 × 107CFU of live H. pylori three times at 2-day intervals. At 6 or 18 weeks after the challenge, mice were sacrificed and bacterial cultures and histological studies of the stomach were performed. Vaccination with 2 mg/session or 200 μg/session inhibited H. pylori colonization by 90 and 100%, respectively. These mice were considered protected. Lower levels of H. pylori-specific immunoglobulin A (IgA) were detected in fecal and saliva samples before challenge. However, a significant increase in IgA secretion in mucosal tissue and a higher labeling index for IgA-positive lumina of pyloric glands were noted in these mice in response to challenge and in a vaccine dose-dependent manner. In protected mice, however, severe gastritis characterized by marked infiltration of inflammation mononuclear cells was noted at 6 weeks after challenge, compared with the gastritis seen in unprotected mice or nonvaccinated, ordinarily infected mice. Marked expression of gamma interferon mRNA was detected in the stomach of all protected mice, and 50% of these mice expressed interleukin 4 (IL-4) or IL-5 mRNA. Our findings suggest that local secretory IgA antibody and severe postimmunization gastritis correlate well with protection of mice against H. pylori infection.

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