Sexual Dimorphism Has Low Impact on the Response against Rotavirus Infection in Suckling Rats

Rotaviruses (RVs) are the leading pathogens causing severe and acute diarrhea in children and animals. It is well known that sex contributes to shaping immune responses, thus it could also influence the incidence and severity of the RV infection. The aim of this study was to analyze the influence of sexual dimorphism on RV infection and its antibody (Ab) immune response in a suckling rat model. Neonatal suckling rats were intragastrically RV-inoculated and clinical indexes derived from fecal samples, as well as immune variables were evaluated. Higher severity of diarrhea, fecal weight and viral elimination were observed in males compared to females (p < 0.05). Regarding the adaptative immunity, the RV shaped the immune response to lower IgG1 levels and an increased Th1/Th2-associated Ab response (p < 0.05). Although females had lower IgG2a levels than males (p < 0.05), the specific anti-RV antibody levels were not sex influenced. In fact, at this age the passive transfer of anti-RV antibodies through breast milk was the critical factor for clustering animals, independently of their sex. It can be concluded that male and female diarrhea severity in RV infection is slightly influenced by sexual dimorphism and is not associated with the specific immune response against the virus.

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Antibody response after COVID-19 mRNA vaccination in relation to age, sex, and side effects

10.1101/2021.04.19.21255714 ◽

2021 ◽

Author(s):

Paul Naaber ◽

Virge Jürjenson ◽

Ainika Adamson ◽

Epp Sepp ◽

Liina Tserel ◽

...

Keyword(s):

Immune Response ◽

Side Effects ◽

Immune Responses ◽

Antibody Response ◽

Older Individuals ◽

High Efficacy ◽

Vaccine Response ◽

Antibody Levels ◽

The Impact ◽

Older Males

AbstractBackgroundThe mRNA vaccines for SARS-CoV2 have proven highly effective and are currently used to vaccinate all age groups against COVID-19. Despite their high efficacy in clinical trials, there is limited data on the impact of age, sex, and side effects on vaccine-induced immune responses.MethodsWe here studied the development of SARS-CoV-2 Spike protein RBD domain antibodies after two doses of the Pfizer-BioNTech Comirnaty mRNA vaccine in 118 healthy volunteers and correlated their immune response with age, sex, and side effects reported after the vaccinations.FindingsOur findings show a robust immune response to the Spike protein’s RBD region after the first and the second vaccination dose. However, we also saw a decline of antibody levels at 6 weeks versus 1 week after the second dose, suggesting a waning of the immune response over time. Regardless of this, the antibody levels at 6 weeks after the second dose remained significantly higher than before the vaccination, after the first dose, or in COVID-19 convalescent individuals. We found a decreased vaccination efficacy but fewer adverse events in older individuals, and that mRNA vaccination is less efficient in older males whereas the detrimental impact of age on vaccination outcome is abolished in females at 6 weeks after the second dose.InterpretationThe Pfizer-BioNTech Comirnaty mRNA vaccine induces a strong immune response after two doses of vaccination but older individuals develop fewer side effects and decreased antibody levels at 6 weeks. The waning of anti-viral antibodies in particular in older male individuals suggests that both age and male sex act as risk factors in the immune response to the SARS-CoV-2 mRNA vaccine.FundingThe study was supported by the Centre of Excellence in Translational Genomics (EXCEGEN), and the Estonian Research Council grant PRG377 and SYNLAB Estonia.Research in contextEvidence before this studyThe first studies addressing the immune responses in older individuals after the single-dose administration of the SARS-CoV-2 mRNA vaccines have been published. We searched PubMed and medRxiv for publications on the immune response of SARS-CoV-2-mRNA vaccines, published in English, using the search terms “SARS-CoV-2”, “COVID-19”, “vaccine response”, “mRNA vaccine”, up to April 15th, 2021. To date, most mRNA vaccine response studies have not been peer-reviewed, and data on the role of age, sex and side effects on SARS-CoV-2-mRNA vaccines in real vaccination situations is limited. Some studies have found a weaker immune response in older individuals after the first dose and these have been measured at a relatively short period (within 1-2 weeks) after the first dose but little longer-term evidence exists on the postvaccination antibody persistence. Even less information is available on sex differences or correlations with mRNA vaccine side effects.Added value of this studyIn this study, we assessed the antibody response up to 6 weeks after the second dose of Pfizer-BioNTech Comirnaty mRNA vaccine in 118 individuals. Our findings show a strong initial immune response after the first dose and an even higher Spike RBD antibody levels at 1 week after the second dose, but these significantly declined at 6 weeks after the second dose. We also found a weaker immune response and faster waning of antibodies in older vaccinated individuals, which correlated with fewer side effects at the time of vaccinations. Furthermore, although overall female and male vaccinees responded similarly, we found that age-related waning of the vaccine-related antibodies was stronger amongst older males whereas in females the impact of age was lost at 6 weeks after the second dose.Implications of all the available evidenceNew mRNA vaccines are now applied worldwide as they have shown high efficacy in clinical trials. Our results show that two doses of Pfizer-BioNTech Comirnaty mRNA vaccine induce a strong antibody response to Spike RBD region but these high levels decline 1.5 months after the second dose in most of the vaccinated individuals. Nevertheless, even at 6 weeks after the second dose, they stay significantly higher than at prevaccination, after the first dose of vaccine, or in Covid-19 postinfection. These findings also implicate that fewer adverse effects may indicate lower antibody response after the vaccination and point to the need for more individualized vaccination protocols, in particular among older people.

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Experimental human pneumococcal colonisation in older adults is feasible and safe, not immunogenic

10.1101/2020.04.23.20077073 ◽

2020 ◽

Author(s):

Hugh Adler ◽

Esther L German ◽

Elena Mitsi ◽

Elissavet Nikolaou ◽

Sherin Pojar ◽

...

Keyword(s):

Older Adults ◽

Immune Response ◽

Immune Responses ◽

Pneumococcal Disease ◽

Bacterial Culture ◽

Invasive Disease ◽

Post Challenge ◽

Nasal Wash ◽

Younger Adults ◽

Antibody Levels

Rationale: Pneumococcal colonisation is key to the pathogenesis of invasive disease, but is also immunogenic in young adults, protecting against re-colonisation. Colonisation is rarely detected in older adults, despite high rates of pneumococcal disease. Objectives: To establish experimental human pneumococcal colonisation in healthy adults aged 50-84 years, to measure the immune response to pneumococcal challenge, and to assess the protective effect of prior colonisation against autologous strain rechallenge. Methods: Sixty-four participants were inoculated with Streptococcus pneumoniae (serotype 6B, 80,000CFU in each nostril). Colonisation was determined by bacterial culture of nasal wash, serum anti-6B capsular IgG responses by ELISA, and anti-protein immune responses by multiplex electrochemiluminescence. Measurements and Main Results: Experimental colonisation was established in 39% of participants (25/64) with no adverse events. Colonisation occurred in 47% (9/19) of participants aged 50-59 compared with 21% (3/14) in those aged 70 years and older. Previous pneumococcal polysaccharide vaccination did not protect against colonisation. Colonisation did not confer serotype-specific immune boosting: GMT (95% CI) 2.7ug/mL (1.9-3.8) pre-challenge versus 3.0 (1.9-4.7) four weeks post-colonisation (p = 0.53). Furthermore, pneumococcal challenge without colonisation led to a drop in specific antibody levels from 2.8ug/mL (2.0-3.9) to 2.2ug/mL (1.6-3.0) post-challenge (p = 0.006). Anti-protein antibody levels increased following successful colonisation. Rechallenge with the same strain after a median of 8.5 months (IQR 6.7-10.1) led to recolonisation in 5/16 (31%). Conclusions: In older adults, experimental pneumococcal colonisation is feasible and safe, but demonstrates different immunological outcomes compared with younger adults in previous studies.

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Early Onset of SARS-COV-2 Antibodies after First Dose of BNT162b2: Correlation with Age, Gender and BMI

Vaccines ◽

10.3390/vaccines9070685 ◽

2021 ◽

Vol 9 (7) ◽

pp. 685

Author(s):

Raul Pellini ◽

Aldo Venuti ◽

Fulvia Pimpinelli ◽

Elva Abril ◽

Giovanni Blandino ◽

...

Keyword(s):

Body Mass Index ◽

Immune Response ◽

Immune Responses ◽

Antibody Titre ◽

Healthcare Workers ◽

Normal Weight ◽

Nasopharyngeal Swab ◽

Priming Dose ◽

And Gender ◽

Antibody Levels

Background: The first goal of the study was to analyse the antibody titre 21 days after the first dose of the BNT162b2 vaccine in a group of 252 healthcare workers (HCW). The second goal was to analyse how the antibody titre changes in correlation with age, gender and body mass index (BMI). Methods: Participants had a nasopharyngeal swab for SARS-CoV-2 and were assessed for the presence of SARS-CoV-2 antibodies at baseline and 21 days after the BNT162b2 priming dose. Results: First dose of BNT162b2 activated immune responses in 98% of the participants. Five HWC had no increase in antibody titre 21 days after the first dose. Antibody titre was greater in young (<38 years) vs. older participants (<38 vs. 47–56 p = 0.002; <38 vs. >56 p = 0.001). Higher antibody levels were detected in underweight vs. pre-obesity group (p = 0.026) and in normal-weight vs. pre-obesity group (p = 0.007). This association was confirmed after adjusting for age (p = 0.0001) and gender (p = 0.00001). Conclusions: Our study demonstrates that a single dose of BNT162b2 activates the immune response, and being young and normal-weight correlate positively with this response. Larger specifically designed clinical trials are needed to validate these results.

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Modulation of parasitemia and antibody responce to Trypanosoma cruzy by cyclophosphamide in Calomys callosus (Rodentia, Cricetidae)

Revista do Instituto de Medicina Tropical de São Paulo ◽

10.1590/s0036-46651992000100001 ◽

1992 ◽

Vol 34 (1) ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Monamaris Marques Borges ◽

Paulo Roberto Curi ◽

Judith Kardos Kloetzel

Keyword(s):

Immune Response ◽

Body Weight ◽

Antibody Response ◽

Passive Transfer ◽

Additional Dose ◽

Wild Rodent ◽

Susceptibility To Infection ◽

Calomys Callosus ◽

Antibody Levels ◽

Cruzi Infection

Calomys callosus a wild rodent, previously described as harboring Trypanosoma cruzi, has a low susceptibility to infection by this protozoan. Experiments were designed to evaluate the contribution of the immune response to the resistance to T. cruzi infection exhibited by C. calossus. Animals were submitted to injections of high (200 mg/kg body weight) and low (20 mg/kg body weight) doses of cyclophosphamide on days -1 or -1 and +5, and inoculated with 4 x 10³ T. cruzi on day O. Parasitemia, mortality and antibody response as measured by direct agglutination of trypomastigotes were observed. Two hundred mg doses of cyclophosphamide resulted in higher parasitemia and mortality as well as in suppression of the antibody response. A single dose of 20 mg enhanced antibody levels on the 20th day after infection, while an additional dose did not further increase antibody production. Parasitemia levels were not depressed, but rather increased in both these groups as compared to untreated controls. Passive transfer of hyperimmune C. callosus anti-T. cruzi serum to cyclophosphamide immunosuppressed animals resulted in lower parasitemia and mortality rates. These results indicate that the immune response plays an important role in the resistance of C. callossus to T. cruzi.

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Development of Dog Immune System: From in Uterus to Elderly

Veterinary Sciences ◽

10.3390/vetsci6040083 ◽

2019 ◽

Vol 6 (4) ◽

pp. 83 ◽

Cited By ~ 3

Author(s):

Maria Pereira ◽

Ana Valério-Bolas ◽

Cátia Saraiva-Marques ◽

Graça Alexandre-Pires ◽

Isabel Pereira da Fonseca ◽

...

Keyword(s):

Immune Response ◽

Immune System ◽

Infectious Diseases ◽

Immune Responses ◽

End Of Life ◽

Great Risk ◽

Passive Transfer ◽

Immune Memory ◽

Physiological Conditions ◽

Current Article

Immune system recognize and fight back foreign microorganisms and inner modifications that lead to deficient cell and tissue functions. During a dog’s life, the immune system needs to adapt to different physiological conditions, assuring surveillance and protection in a careful and controlled way. Pregnancy alters normal homeostasis, requiring a balance between immunity and tolerance. The embryos and fetus should be protected from infections, while the female dog must tolerate the growing of semi-allografts in her uterus. After birth, newborn puppies are at great risk of developing infectious diseases, because their immune system is in development and immune memory is absent. Passive transfer of immunity through colostrum is fundamental for puppy survival in the first weeks of life, but hampers the development of an active immune response to vaccination. At the end of life, dogs experience a decline in the structure and functional competence of the immune system, compromising the immune responses to novel antigenic challenges, such as infections and vaccines. Therefore, the current article reviews the general processes related to the development of the dog´s immune system, providing an overview of immune activity throughout the dog’s life and its implications in canine health, and highlighting priority research goals.

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Immune response toTrichinellaepitopes: the antiphosphorylcholine plaque-forming cell response during the biological cycle

Parasitology ◽

10.1017/s0031182000055888 ◽

1987 ◽

Vol 94 (3) ◽

pp. 543-553 ◽

Cited By ~ 26

Author(s):

F. M. Ubeira ◽

J. Leiro ◽

M. T. Santamarina ◽

T. G. Villa ◽

M. L. Sanmartín-Durán

Keyword(s):

Immune Response ◽

Immune Responses ◽

Blood Cells ◽

Microsomal Fraction ◽

Trichinella Spiralis ◽

Natural Infection ◽

Biological Cycle ◽

Spleen Cells ◽

Large Numbers ◽

Antibody Levels

Phosphorylcholine (PC), an immunodominant component of the cell wall of certain bacteria, fungi and nematodes, is known to induce low anti-PC antibody levels during natural infection byTrichinella spiralis. This article reports a study in which spleen cells from BCF1 mice infected withTrichinellasp. larvae were found to produce large numbers of direct haemolytic plaques in response to PC conjugated to sheep red blood cells (SRBC) after muscle-encysted larvae had been killed by treatment with mebendazole. Inhibition of the response by PC-chloride, immunodiffusion and immunoelectrophoretic studies with the anti-PC IgA (TEPC-15) and anti-idiotype T15 serum assays showed the plaque-forming cell (PFC) response to be specific for PC. The absence of haemolytic plaques when unconjugated SRBC or TNP-SRBC were used as indicator cells ruled out involvement of a polyclonal response. Greatest anti-PC PFC response was found to be associated with a microsomal fraction designated FCpl, a particulate fraction behaving as a thymus-dependent antigen. The FCpl fractions from all four strains ofTrichinellaemployed induced anti-PC PFC responses when injected into mice. These results suggest that FCpl is a suitable antigen for use in detailed studies of immune responses toTrichinellaand related parasites.

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Poria cocos polysaccharide induced Th1-type immune responses to ovalbumin in mice

PLoS ONE ◽

10.1371/journal.pone.0245207 ◽

2021 ◽

Vol 16 (1) ◽

pp. e0245207

Author(s):

Xiaoxiao Dong ◽

Boye Li ◽

Boyang Yu ◽

Tian Chen ◽

Qin Hu ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Immune Responses ◽

Surface Expression ◽

Poria Cocos ◽

Murine Bone Marrow ◽

Enhanced Production ◽

Ifn Γ ◽

Cellular Immune ◽

Antibody Levels

In the present study, we evaluated adjuvant potential of Poria cocos polysaccharide (PCP) on the Th1-type immune responses of C57/BL6 mice against ovalbumin (OVA). We first determined the effect of PCP on maturation of murine bone marrow derived dendritic cells (BMDCs), PCP significantly upregulated surface expression of MHCII, CD40, CD80, CD86 and enhanced production of IL-6 and IL-12p40. In addition, PCP affected receptor-mediated endocytosis, but not pinocytosis in BMDCs. Furthermore, OVA + PCP immunization induced specific cytotoxic CD8+ T cell killing of OVA (257–264) peptide pulsed cell. When mice were immunized subcutaneously in a week interval with OVA + PCP. Serum were collected for measuring OVA-specific antibody and splenocytes were harvested for analyzing CD69, IFN-γ ELISpot and cytokines production. The result indicated that OVA-specific IgG, IgG2a and IgG1 antibody levels in serum were significantly elevated by PCP compared with control. PCP increased OVA-specific IFN-γ-secreting CD8+, CD4+ T cells, promoted CD8+ T cell proliferation and up-regulated Th-1 type (IFN-γ, IL-2) cytokine production. In conclusion, data suggest that PCP enhanced cellular immune response and possess potential as a vaccine adjuvant for Th1 immune response.

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17β-Estradiol Is Involved in the Sexual Dimorphism of the Immune Response to Malaria

Frontiers in Endocrinology ◽

10.3389/fendo.2021.643851 ◽

2021 ◽

Vol 12 ◽

Author(s):

Luis Antonio Cervantes-Candelas ◽

Jesús Aguilar-Castro ◽

Fidel Orlando Buendía-González ◽

Omar Fernández-Rivera ◽

Teresita de Jesús Nolasco-Pérez ◽

...

Keyword(s):

Immune Response ◽

Sexual Dimorphism ◽

Immune Responses ◽

Mrna Expression ◽

Intact Female ◽

Expression Levels ◽

Female Mice ◽

17Β Estradiol ◽

The Brain ◽

Mrna Expression Levels

Malaria is the leading cause of parasitic infection-related death globally. Additionally, malaria-associated mortality is higher in men than in women, and this sexual dimorphism reflects differences in innate and adaptive immune responses that are influenced by sex hormones. Normally, females develop more robust immune responses against parasites than males. However, most clinical and laboratory studies related to the immune response to malaria do not consider sex as a variable, and relatively few studies have compared the sex-dependent role of 17β-estradiol in this process. In this study, we decreased in vivo the levels of 17β-estradiol by gonadectomy or administered 17β-estradiol to intact or gonadectomized male and female CBA/Ca mice infected with Plasmodium berghei ANKA. Subsequently, we assessed the effects of 17β-estradiol on parasite load; the percentages of different immune cells in the spleen; the plasma levels of antibodies and pro- and anti-inflammatory cytokines; and the mRNA expression levels of cytokine-encoding genes in the brain. The results showed that the administration of 17β-estradiol increased parasitemia and decreased body weight in intact female mice. Moreover, intact females exhibited higher levels of CD8+ T cells and lower levels of NK1.1+ cells than their male counterparts under the same condition. Gonadectomy increased IFN-γ and decreased TNF-α concentrations only in intact female mice. Additionally, IL-10 levels were higher in intact females than in their male counterparts. Finally, the mRNA expression levels of cytokines coding genes in the brain showed a dimorphic pattern, i.e., gonadectomy upregulated Tnf, Il1b, and Il10 expression in males but not in females. Our findings explain the sexual dimorphism in the immune response to malaria, at least in part, and suggest potential sex-dependent implications for the efficacy of vaccines or drugs targeting malaria.

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COVID-19 mRNA Vaccination in Lactation: Assessment of Adverse Events and Vaccine Related Antibodies in Mother-Infant Dyads

Frontiers in Immunology ◽

10.3389/fimmu.2021.777103 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yarden Golan ◽

Mary Prahl ◽

Arianna G. Cassidy ◽

Caryl Gay ◽

Alan H. B. Wu ◽

...

Keyword(s):

Immune Response ◽

Adverse Events ◽

Immune Responses ◽

Maternal Plasma ◽

Receptor Binding Domain ◽

Igg Antibodies ◽

Blood Samples ◽

Milk Samples ◽

Automated Immunoassay ◽

Antibody Levels

BackgroundData regarding symptoms in the lactating mother-infant dyad and their immune response to COVID-19 mRNA vaccination during lactation are needed to inform vaccination guidelines.MethodsFrom a prospective cohort of 50 lactating individuals who received mRNA-based vaccines for COVID-19 (mRNA-1273 and BNT162b2), blood and milk samples were collected prior to first vaccination dose, immediately prior to 2nd dose, and 4-10 weeks after 2nd dose. Symptoms in mother and infant were assessed by detailed questionnaires. Anti-SARS-CoV-2 antibody levels in blood and milk were measured by Pylon 3D automated immunoassay and ELISA. In addition, vaccine-related PEGylated proteins in milk were measured by ELISA. Blood samples were collected from a subset of infants whose mothers received the vaccine during lactation (4-15 weeks after mothers’ 2nd dose).ResultsNo severe maternal or infant adverse events were reported in this cohort. Two mothers and two infants were diagnosed with COVID-19 during the study period before achieving full immune response. PEGylated proteins were not found at significant levels in milk after vaccination. After vaccination, levels of anti-SARS-CoV-2 IgG and IgM significantly increased in maternal plasma and there was significant transfer of anti-SARS-CoV-2-Receptor Binding Domain (anti-RBD) IgA and IgG antibodies to milk. Milk IgA levels after the 2nd dose were negatively associated with infant age. Anti-SARS-CoV-2 IgG antibodies were not detected in the plasma of infants whose mothers were vaccinated during lactation.ConclusionsCOVID-19 mRNA vaccines generate robust immune responses in plasma and milk of lactating individuals without severe adverse events reported.

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Transgenic Expression of a Mosquito-Stage Malarial Protein, Pbs21, in Blood Stages of Transformed Plasmodium bergheiand Induction of an Immune Response upon Infection

Infection and Immunity ◽

10.1128/iai.66.8.3884-3891.1998 ◽

1998 ◽

Vol 66 (8) ◽

pp. 3884-3891 ◽

Cited By ~ 12

Author(s):

Gabriele Margos ◽

Melissa R. van Dijk ◽

Jai Ramesar ◽

Chris J. Janse ◽

Andrew P. Waters ◽

...

Keyword(s):

Immune Response ◽

Plasmodium Berghei ◽

Promoter Region ◽

Surface Protein ◽

Wild Type ◽

Natural Control ◽

Male And Female ◽

Transgenic Expression ◽

Antibody Levels ◽

Flanking Regions

ABSTRACT Pbs21 is a surface protein of the ookinete of Plasmodium berghei, which can induce a potent transmission-blocking immune response. Pbs21 is normally expressed only by parasite stages in the mosquito, i.e., female gametes/zygotes, ookinetes, and oocysts. However, the Pbs21 gene is transcribed in female gametocytes which circulate in the bloodstream of the host, where translation of the resulting mRNA is totally repressed. Episomal transfection has been used to investigate whether expression of Pbs21 protein could be achieved in blood stages of the parasite. By using plasmid pMD221, the complete mRNA-encoding region of Pbs21, flanked only by 218 nucleotides (nt) of its promoter region and 438 nt of its 3′ region downstream from the polyadenylation site, was introduced into the blood stages of gametocyte-producing and non-gametocyte-producing clones of P. berghei. In both of these transformed parasite lines, Pbs21 protein was expressed in asexual trophozoites, schizonts, and, when present, in both male and female gametocytes. Hence, the flanking regions present are sufficient to allow transcription but lack the elements that exert natural control of sex- and stage-specific transcription. The mRNA and the protein expressed by transformed blood stages were indistinguishable from the wild-type forms by the criteria tested, and the protein was recognized by both conformation-dependent and conformation-independent monoclonal antibodies raised against native Pbs21. In mice infected with transformed non-gametocyte-producing parasites, a Pbs21-specific immune response was induced and characterized with respect to isotype (IgG2a/IgG2b) and quantity (11.5 ± 10 μg/ml) of antibody produced. However, as found in previous studies, these antibody levels were insufficient to inhibit development of the parasites in the mosquito. The ability to express mosquito midgut-stage antigens in blood-stage parasites will facilitate further investigations of molecular and immunological properties of these proteins.

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