α-galactosylceramide-reactive NKT cells increase IgG1 class switch against a C. difficile polysaccharide antigen and enhance immunity against a live pathogen challenge

2021 ◽  
Author(s):  
Gillian A. Lang ◽  
Binu Shrestha ◽  
Souwelimatou Amadou Amani ◽  
Tyler Shadid ◽  
Jimmy D. Ballard ◽  
...  
Keyword(s):  
Immune Response ◽  
Nkt Cells ◽  
Antibody Responses ◽  
Polysaccharide Antigen ◽  
Protein Carrier ◽  
Humoral Immune ◽  
Class Switch ◽  
Clostridioides Difficile ◽  
Pathogen Challenge ◽  
Modest Effect

All clinical Clostridioides difficile strains identified to date express a surface capsule-like polysaccharide structure known as polysaccharide II (PSII). The PSII antigen is immunogenic and when conjugated to a protein carrier induces a protective antibody response in animal models. Given that CD1d-restricted Natural Killer T (NKT) cells promote antibody responses, including those against carbohydrates, we tested the hypothesis that immunization with PSII and a CD1d-binding glycolipid adjuvant could lead to enhanced protection against a live C. difficile challenge. We purified PSII from a clinical isolate of C. difficile and immunized B6 mice with PSII alone or PSII plus the CD1d-binding glycolipid α-galactosylceramide (α-GC). PSII-specific IgM and IgG titers were evident in sera from immunized mice. The inclusion of α-GC had a modest influence on isotype switch but increasing the ratio of IgG1/IgG2c. Enhanced protection against C. difficile disease was achieved by inclusion of the α-GC ligand and was associated with reduced bacterial numbers in fecal pellets. In contrast, NKT-deficient Traj18 -/- mice were not protected by the PSII/α-GC immunization modality. Absence of NKT cells similarly had a modest effect on isotype switch but ratios of IgG1/IgG2c decreased. These results indicate that α-GC-driven NKT cells move the humoral immune response against C. difficile PSII antigen towards Th2-driven IgG1 and may contribute to augmented protection. This study suggests that NKT activation represents a pathway for additional B cell help that could be used to supplement existing efforts to develop vaccines against polysaccharides derived from C. difficile and other pathogens.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously infected to SARS-CoV-2 subjects and not infected to SARS-CoV-2 subjects. Methods We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated. Results Both previously infected and not infected to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-infected subjects in comparison to titers of not infected subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously infected to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ($$ \overline{x} $$ x ¯ =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose. Conclusions The results showed that, as early as the first dose, SARS-CoV-2-infected individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-infected subjects. FC for previously infected subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not infected subjects, after the second dose, were = 3.8 in > 45.0% of vaccinees, and ≤ 3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

scholarly journals Long-term maternal effect on offspring immune response in song sparrows Melospiza melodia

2006 ◽  
Vol 2 (4) ◽  
pp. 573-576 ◽  
Author(s):  
Jane M Reid ◽  
Peter Arcese ◽  
Lukas F Keller ◽  
Dennis Hasselquist
Keyword(s):  
Immune Response ◽  
Time Scales ◽  
Parasitic Infection ◽  
Antibody Responses ◽  
Melospiza Melodia ◽  
Long Term Effects ◽  
Free Living ◽  
Humoral Immune ◽  
Song Sparrows

Knowledge of the causes of variation in host immunity to parasitic infection and the time-scales over which variation persists, is integral to predicting the evolutionary and epidemiological consequences of host–parasite interactions. It is clear that offspring immunity can be influenced by parental immune experience, for example, reflecting transfer of antibodies from mothers to young offspring. However, it is less clear whether such parental effects persist or have functional consequences over longer time-scales, linking a parent's previous immune experience to future immune responsiveness in fully grown offspring. We used free-living song sparrows ( Melospiza melodia ) to quantify long-term effects of parental immune experience on offspring immune response. We experimentally vaccinated parents with a novel antigen and tested whether parental vaccination influenced the humoral antibody response mounted by fully grown offspring hatched the following year. Parental vaccination did not influence offspring baseline antibody titres. However, offspring of vaccinated mothers mounted substantially stronger antibody responses than offspring of unvaccinated mothers. Antibody responses did not differ between offspring of vaccinated and unvaccinated fathers. These data demonstrate substantial long-term effects of maternal immune experience on the humoral immune response of fully grown offspring in free-living birds.

scholarly journals Antibody Responses to Bovine Alphaherpesvirus 1 (BoHV-1) in Passively Immunized Calves

Viruses ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 23 ◽  
Author(s):  
Stefano Petrini ◽  
Carmen Iscaro ◽  
Cecilia Righi
Keyword(s):  
Immune Response ◽  
Diagnostic Tests ◽  
Vaccine Virus ◽  
Antibody Responses ◽  
Infectious Bovine Rhinotracheitis ◽  
Glycoprotein E ◽  
Marker Vaccine ◽  
Humoral Immune ◽  
Double Deletion ◽  
Antibody Kinetics

To date, in countries where infectious bovine rhinotracheitis (IBR) is widespread, its control is associated with deleted marker vaccines. These products lack one or more genes responsible for the synthesis of glycoproteins or enzymes. In Europe, the most widely used marker vaccine is one in which glycoprotein E (gE−) is deleted, and it is marketed in a killed or modified-live form. Using this type of immunization, it is possible to differentiate vaccinated animals (gE−) from those infected or injected with non-deleted (gE+) products using diagnostic tests specific for gE. The disadvantage of using modified-live gE-products is that they may remain latent in immunized animals and be reactivated or excreted following an immunosuppressive stimulus. For this reason, in the last few years, a new marker vaccine became commercially available containing a double deletion related to genes coding for gE and the synthesis of the thymidine-kinase (tk) enzyme, the latter being associated with the reduction of the neurotropism, latency, and reactivation of the vaccine virus. Intramuscularly and intranasally administered marker products induce a humoral immune response; however, the mother-to-calf antibody kinetics after vaccination with marker vaccines is poorly understood. This review discusses several published articles on this topic.

scholarly journals Depletion of Complement Has Distinct Effects on the Primary and Secondary Antibody Responses to a Conjugate of Pneumococcal Serotype 14 Capsular Polysaccharide and a T-Cell-Dependent Protein Carrier

2005 ◽  
Vol 73 (1) ◽  
pp. 277-286 ◽  
Author(s):  
Samuel T. Test ◽  
Joyce K. Mitsuyoshi ◽  
Yong Hu
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Antibody Response ◽  
Complement Activation ◽  
Capsular Polysaccharide ◽  
Antibody Responses ◽  
Primary Immunization ◽  
Protein Carrier ◽  
Dependent Protein

ABSTRACT Complement activation plays a critical role in the immune response to T-cell-dependent and T-cell-independent antigens. However, the effect of conjugation of T-cell-dependent protein carriers to T-cell-independent type 2 antigens on the requirement for complement in the humoral immune response to such antigens remains unknown. We studied the role of complement activation on the antibody response of BALB/c mice immunized with the T-cell-independent type 2 antigen serotype 14 pneumococcal capsular polysaccharide (PPS14), either in unmodified form or conjugated to ovalbumin (OVA). In mice immunized with either PPS14 or PPS14-OVA, depletion of endogenous complement at the time of primary immunization by treatment with cobra venom factor (CVF) diminished serum anti-PPS14 concentrations after primary immunization but enhanced antibody responses after secondary immunization. The secondary immunoglobulin G (IgG) anti-PPS14 antibody response after immunization with PPS14-OVA was especially enhanced by complement depletion, was observed at doses as low as 0.2 μg of antigen, and was maximal when CVF was administered within 2 days of immunization. The avidity and opsonophagocytic functions of IgG anti-PPS14 antibodies were comparable in mice immunized with PPS14-OVA with or without complement depletion. Serum anti-PPS14 antibody concentrations were near normal, and the enhancing effects of CVF treatment on the secondary anti-PPS14 antibody response were also apparent in splenectomized mice immunized with PPS14-OVA. These results demonstrate that complement activation can have distinct effects on the primary and secondary antibody responses to a T-cell-independent type 2 antigen, either unmodified or conjugated to a T-cell-dependent protein carrier. These differences should be taken into consideration when using complement to modulate the immune response to vaccines.

scholarly journals Induction of a Specific Humoral Immune Response by Nasal Delivery of Bcla2ctd of Clostridioides difficile

2020 ◽  
Vol 21 (4) ◽  
pp. 1277 ◽  
Author(s):  
Ana Raquel Maia ◽  
Rodrigo Reyes-Ramírez ◽  
Marjorie Pizarro-Guajardo ◽  
Anella Saggese ◽  
Pablo Castro-Córdova ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Surface Protein ◽  
Developed Countries ◽  
Nasal Delivery ◽  
Experimental Conditions ◽  
Humoral Immune ◽  
Clostridioides Difficile

Clostridioides difficile, formerly known as Clostridium difficile, is a spore-forming bacterium considered as the most common cause of nosocomial infections in developed countries. The spore of C. difficile is involved in the transmission of the pathogen and in its first interaction with the host; therefore, a therapeutic approach able to control C. difficile spores would improve the clearance of the infection. The C-terminal (CTD) end of BclA2, a spore surface protein of C. difficile responsible of the interaction with the host intestinal cells, was selected as a putative mucosal antigen. The BclA2 fragment, BclA2CTD, was purified and used to nasally immunize mice both as a free protein and after adsorption to the spore of Bacillus subtilis, a well-established mucosal delivery vehicle. While the adsorption to spores increased the in vitro stability of BclA2CTD, in vivo both free and spore-adsorbed BclA2CTD were able to induce a similar, specific humoral immune response in a murine model. Although in the experimental conditions utilized the immune response was not protective, the induction of specific IgG indicates that free or spore-bound BclA2CTD could act as a putative mucosal antigen targeting C. difficile spores.

scholarly journals A genetic basis for atrophy: dominant non-responsiveness and helicobacter induced gastritis in F1 hybrid mice

Gut ◽  
1999 ◽  
Vol 45 (3) ◽  
pp. 335-340 ◽  
Author(s):  
P Sutton ◽  
J Wilson ◽  
R Genta ◽  
D Torrey ◽  
A Savinainen ◽  
...  
Keyword(s):  
Immune Response ◽  
Serum Antibody ◽  
Antibody Responses ◽  
Host Factors ◽  
Mouse Strains ◽  
F1 Hybrid ◽  
Helicobacter Felis ◽  
Humoral Immune ◽  
Antibody Levels ◽  
Hybrid Mice

BACKGROUNDThe importance of host factors in helicobacter induced gastritis has been shown in animal models. Infection of most mouse strains withHelicobacter felis results in a functional atrophic gastritis, while other strains remain gastritis free.AIMSTo investigate these host factors further by using genetic crosses of responder and non-responder mice.METHODSF1 hybrids of the non-responder CBA/Ca strain and three strains of mice known to develop H felis induced gastritis were infected for three months with H felis. Gastritis was assessed by histopathology and serum antibody responses by ELISA.RESULTSInfection of CBA/Ca mice and F1 hybrids induced little or no gastritis. Analyses of the antibody responses in these mice revealed virtually undetectable anti-helicobacter antibody levels despite colonisation with high numbers of H felis. In contrast, infection of H felis responsive strains induced gastritis and a significant humoral immune response.CONCLUSIONSThe non-responsiveness of CBA/Ca mice to H felis infection is dominantly inherited. The lack of gastritis in CBA mice and their offspring is probably due to active suppression of the immune response normally mounted against H felis. Investigation of these mechanisms will provide important insights relevant to induction of gastric atrophy and cancer in humans.

scholarly journals Caprine humoral response to Burkholderia pseudomallei antigens during acute melioidosis from aerosol exposure

2018 ◽  
Author(s):  
Jinhee Yi ◽  
Mukoma F. Simpanya ◽  
Erik W. Settles ◽  
Austin B. Shannon ◽  
Karen Hernandez ◽  
...  
Keyword(s):  
Immune Response ◽  
Humoral Immune Response ◽  
Burkholderia Pseudomallei ◽  
Humoral Response ◽  
Antibody Responses ◽  
Protein Profiling ◽  
Common Source ◽  
Humoral Immune ◽  
Antigenic Proteins ◽  
Immunogenic Proteins

AbstractBurkholderia pseudomalleicauses melioidosis, a common source of pneumonia and sepsis in Southeast Asia and Northern Australia, that results in high mortality rates. A caprine melioidosis model of aerosol infection that leads to a systemic infection has the potential to characterize the humoral immune response. This could help identify immunogenic proteins for new diagnostics and vaccine candidates. Outbred goats may more accurately mimic human infection, in contrast to the inbred mouse models used to date.B. pseudomalleiinfection was delivered as an intratracheal aerosol. Antigenic protein profiling was generated from the infecting strain MSHR511. Humoral immune responses were analyzed by ELISA and western blot, and the antigenic proteins were identified by mass spectrometry. Throughout the course of the infection the assay results demonstrated a much greater humoral response with IgG antibodies, in both breadth and quantity, compared to IgM antibodies. Pre-infection sera showed multiple immunogenic proteins already reactive for IgG (7-20) and IgM (0-12) in most of the goats despite no previous exposure toB. pseudomallei. After infection, the number of IgG reactive proteins showed a marked increase as the disease progressed. Early stage infection (day 7) showed immune reaction to chaperone proteins (GroEL, EF-Tu, and DnaK). These three proteins were detected in all serum samples after infection, with GroEL immunogenically dominant. Seven common reactive antigens were selected for further analysis using ELISA. The heat shock protein GroEL1 elicited the strongest goat antibody immune response compared to the other six antigens. Most of the six antigens showed the peak IgM reactivity at day 14, whereas the IgG reactivity increased further as the disease progressed. An overall MSHR511 proteomic comparison between the goat model and human sera showed that many immune reactive proteins are common between humans and goats with melioidosis.Author SummaryB. pseudomalleiinfection, the causative agent of melioidosis, results in severe disseminated or localized infections. A systemic study of the humoral immune response toB. pseudomalleiinfection using theB. pseudomalleiaerosol caprine model would help understand the detectable antigenic proteins as the infection progresses. To study the immune response, IgG and IgM antibody responses to whole cell lysate proteins were identified and analyzed. Antigenic carbohydrates were also studied. From the results, this study suggests that the caprine humoral immune response to aerosolizedB. pseudomalleihas similarities to human melioidosis and may facilitate the analysis of the temporal antibody responses. In addition, commonly detected immunogenic proteins may be used as biomarkers for the future point of care (POC) diagnostics.

scholarly journals A comparative analysis of memory B cell and antibody responses against Plasmodium falciparum merozoite surface protein 1 in children and adults from Uganda

2021 ◽  
Author(s):  
S Jake Gonzales ◽  
Kathleen N Clarke ◽  
Gayani Batugedara ◽  
Ashley E Braddom ◽  
Rolando Garza ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
B Cells ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Amino Acid Substitutions ◽  
Humoral Immune ◽  
Merozoite Surface Protein 1 ◽  
Specific Igg

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against P. falciparum develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, merozoite surface protein 1 (MSP1), in individuals from a region in Uganda with high P. falciparum transmission. Our results showed that MSP1-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ MSP1-specific classical MBCs. In contrast, anti-MSP1 plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against MSP1 and whole merozoites, with broadening of the response against non-3D7 strains in adults. The antibodies encoded by MSP1-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable MSP1 protein. Proteomics analysis of MSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to MSP1-specific MBCs, anti-MSP1 IgGs had relatively high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the MSP1-specific humoral immune response with cumulative P. falciparum exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of MSP1 variants by the plasma IgG repertoire.

scholarly journals Vaccination strategy and anti - SARS-CoV-2 S titers in healthcare workers of the INT – IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy)

2021 ◽  
Author(s):  
Ernesta Cavalcanti ◽  
Maria Antonietta Isgrò ◽  
Domenica Rea ◽  
Lucia Di Capua ◽  
Giusy Trillò ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Healthcare Workers ◽  
Geometric Mean ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Cancer Center ◽  
Serum Samples ◽  
Humoral Immune ◽  
History Of

Abstract Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and the resulting disease, coronavirus disease 2019 (COVID-19), have spread to millions of people globally, requiring the development of billions of different vaccine doses. The SARS-CoV-2 spike mRNA vaccine (named BNT162b2/Pfizer), authorized by the FDA, has shown high efficacy in preventing SARS-CoV-2 infection after administration of two doses in individuals 16 years of age and older. In the present study, we retrospectively evaluated the differences in the SARS-CoV-2 humoral immune response after vaccine administration in the two different cohorts of workers at the INT - IRCCS “Fondazione Pascale” Cancer Center (Naples, Italy): previously exposed to SARS-CoV-2 subjects and not exposed to SARS-CoV-2 subjects.Methods: We determined specific anti-RBD (receptor-binding domain) titers against trimeric spike glycoprotein (S) of SARS-CoV-2 by Roche Elecsys Anti-SARS-CoV-2 S immunoassay in serum samples of 35 healthcare workers with a previous documented history of SARS-CoV-2 infection and 158 healthcare workers without, after 1 and 2 doses of vaccine, respectively. Moreover, geometric mean titers and relative fold changes (FC) were calculated.Results: Both previously exposed and not exposed to SARS-CoV-2 subjects developed significant immune responses to SARS-CoV-2 after the administration of 1 and 2 doses of vaccine, respectively. Anti-S antibody responses to the first dose of vaccine were significantly higher in previously SARS-CoV-2-exposed subjects in comparison to titers of not exposed subjects after the first as well as the second dose of vaccine. Fold changes for subjects previously exposed to SARS-CoV-2 was very modest, given the high basal antibody titer, as well as the upper limit of 2500.0 BAU/mL imposed by the Roche methods. Conversely, for naïve subjects, mean fold change following the first dose was low ( =1.6), reaching 3.8 FC in 72 subjects (45.6%) following the second dose.Conclusions: The results showed that, as early as the first dose, SARS-CoV-2-exposed individuals developed a remarkable and statistically significant immune response in comparison to those who did not contract the virus previously, suggesting the possibility of administering only one dose in previously SARS-CoV-2-exposed subjects. FC for previously exposed subjects should not be taken into account for the generally high pre-vaccination values. Conversely, FC for not exposed subjects, after the second dose, were = 3.8 in >45.0% of vaccinees, and ≤3.1 in 19.0%, the latter showing a potential susceptibility to further SARS-CoV-2 infection.

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