Differences In Antibody Responses Research Articles

Can Breast Implants Induce Breast Cancer Immunosurveillance? An Analysis of Antibody Response to Breast Cancer Antigen following Implant Placement.

Women with cosmetic breast implants have significantly lower rates of subsequent breast cancer than the general population (relative risk, 0.63; 95 percent CI, 0.56 to 0.71). The authors hypothesize that breast implant-induced local inflammation stimulates immunosurveillance recognition of breast tumor antigen. Sera were collected from two cohorts of healthy women: women with long-term breast implants (i.e., breast implants for >6 months) and breast implant-naive women. Antibody responses to breast tumor antigens were tested by enzyme-linked immunosorbent assay and compared between cohorts by unpaired t test. Of the implant-naive cohort, nine women underwent breast augmentation, and antibody responses before and after implant placement were compared by paired t test. Sera were collected from 104 women: 36 (34.6 percent) long-term breast implants and 68 (65.4 percent) implant-naive women. Women with long-term breast implants had higher antibody responses than implant-naive women to mammaglobin-A (optical density at 450 nm, 0.33 versus 0.22; p = 0.003) and mucin-1 (optical density at 450 nm, 0.42 versus 0.34; p = 0.02). There was no difference in antibody responses to breast cancer susceptibility gene 2, carcinoembryonic antigen, human epidermal growth factor receptor-2, or tetanus. Nine women with longitudinal samples preoperatively and 1 month postoperatively demonstrated significantly elevated antibody responses following implant placement to mammaglobin-A (mean difference, 0.13; p = 0.0002) and mucin-1 (mean difference 0.08; p = 0.02). There was no difference in postimplant responses to other breast tumor antigens, or tetanus. Women with long-term breast implants have higher antibody recognition of mammaglobin-A and mucin-1. This study provides the first evidence of implant-related immune responses to breast cancer antigens. Therapeutic, V.

Sex differences in antibody responses to the 23-valent pneumococcal polysaccharide vaccination

There are profound sex-based differences in both humoral and cellular immune responses to vaccination.1 In general, women have higher antibody responses to bacterial and viral vaccines than men.2 For instance, women vaccinated with half the dose of the trivalent inactivated influenza vaccine produce similar humoral immune responses than men vaccinated with a full dose of the vaccine.3 Given that the 23-valent pneumococcal polysaccharide vaccine (PPSV23) is an important tool in our evaluation of the humoral immune response,4 we sought to reveal whether men and women have a different immunoglobulin G (IgG) antibody response to PPSV23.

Elite athletes with COVID-19 — Predictors of the course of disease

ObjectivesThe aim of the study was to identify predictors determining the course of COVID-19 and antibody response in elite athletes. DesignObservational study. MethodsRoutine medical screening with physical examination, resting ECG, and laboratory tests including antibody response was performed 12–68 days after the diagnosis of COVID-19 in 111 athletes of different sports. ResultsClinical symptoms were observed in 84% of subjects. The severity of COVID-19 was mild in 82% of athletes and moderate in 2% of cases. Athletes aged above 26 and male were more likely to develop symptomatic COVID-19. Asymptomatic subjects were younger and predominantly female. In 18% of subjects, symptoms were still present 20 (12–68) days (median and range) since positive diagnosis. Antibody response was observed in 88% of athletes, and its magnitude correlated with time since diagnosis of COVID-19 (RT-PCR), fatigue, fever, and conjunctivitis. There were no differences in antibody response between groups distinguished by sports discipline (p = 0.50), and sex (p = 0.59), and antibody response did not correlate with BMI (p = 0.12), age (p = 0.13), the number of symptoms (p = 0.43) or their duration (p = 0.19). ConclusionsThe severity of COVID-19 in elite athletes is predominantly mild and without complications. Athletes can return to sport after two symptom-free weeks and additional heart screening is usually not required. Determination of antibodies has been shown to be a useful indicator of a previous COVID-19 disease, and some symptoms can be used as predictors of antibody response.

Initial observations on age, gender, BMI and hypertension in antibody responses to SARS-CoV-2 BNT162b2 vaccine.

BackgroundLiterature data suggests that age, gender and body mass index (BMI) could be associated with difference in immune responses to vaccines. The first goal of the study was to analyze the antibody titre seven days after the second dose of BNT162b2 vaccine in a group of 248 healthcare workers (HCWs). The second goal was to analyze how antibody titre changes in correlation with age, gender, BMI and hypertension.MethodsAn immunogenicity evaluation was carried out among HCWs vaccinated at the Istituti Fisioterapici Ospitalieri (IFO), Rome, Italy. All HCWs were asked to be vaccinated by the Italian national vaccine campaign at the beginning of 2021. 260 vaccinated HCWs were enrolled in the study. All eligible participants were assigned to receive the priming dose in two weeks’ time and the booster dose exactly 21 days thereafter. Blood and nasopharyngeal swabs were collected at baseline and 7 days after second dose of vaccine. Quantitative measurements of IgG antibodies against S1/S2 antigens of SARS-CoV-2 were performed with a commercial chemiluminescent immunoassay. Presence of SARS-Cov-2 in nasopharyngeal swab was determined by commercial RT-PCR testing.Findings248 HWCs were analyzed, 158 women (63.7%) and 90 men (36.3%). After the second dose of BNT162b2 vaccine, 99.5% of participants developed a humoral immune response. The geometric mean concentration of antibodies among the vaccinated subjects after booster dose (285.9 AU/mL 95% CI: 249.5–327.7) was higher than that of human convalescent sera (39.4 AU/mL, 95% CI: 33.1–46.9), with p<0.0001. Multivariate linear regression analysis of AU/mL by age, gender and BMI multivariate was performed by the inclusion of covariates. This analysis demonstrated that age (p<0.0001) and gender (p = 0.038) are statistically associated with differences in antibody response after vaccination, whereas BMI and hypertension have no statistically significant association (p = 0.078 and p = 0.52 respectively).Interpretation99.5% of HCW developed a humoral immune response and female and young participants seem to have an increased capacity to mount humoral immune responses. BMI and hypertension seem not associated with difference in immune response to the vaccine.FundingNone.

Dynamic Antibody Responses in Patients with Different Severity of COVID-19: A Retrospective Study.

IntroductionThe coronavirus disease 2019 (COVID-19) pandemic is a serious public health event and poses a global health threat. To study the specific antibody responses would contribute to a better understanding of COVID-19.MethodsWe collected complete follow-up data from 777 patients with pathogen-confirmed COVID-19 with corresponding immunoglobulin G and M (IgG/IgM) testing results.ResultsOverall, the positive rates of IgG and IgM in severe patients were slightly higher than those in non-severe patients. In addition, higher IgG levels were detected in severe patients compared to non-severe patients (P = 0.026). Through further analysis, differences in IgG were only significant in serum samples taken in the first 14 days of disease onset (P < 0.001). On the basis of analysis of antibody expression levels at different time points in 74 patients who had undergone more than three detection tests, we found that the differences in IgG levels between the severe/non-severe patients were more pronounced than those of IgM. On multivariate logistic regression, after adjusting for cofactors, the higher anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) IgG levels observed in the first 14 days of disease onset were independently associated with severe COVID-19 disease (odds ratio (OR) = 1.368, 95% confidence interval (CI) 1.138–1.645).ConclusionWe observed differences in antibody responses among patients with different severity of COVID-19. A high IgG level in the first 14 days of disease may be positively associated with disease severity.

Blood group O convalescent plasma donations have significantly lower levels of SARS-CoV-2 IgG antibodies compared to blood group A donations.

BackgroundCOVID‐19 convalescent plasma (CCP) is plasma collected from individuals who have recovered from SARS‐CoV‐2 infection. The FDA Emergency Use Authorization restricts use of CCP to high‐titer units only. The purpose of this study was to determine if donor ABO blood group was associated with SARS‐CoV‐2 antibody response, and subsequent qualification as high‐titer CCP.MethodsAll CCP donations collected from April 21, 2020 to September 1, 2020 were included. The Abbott ARCHITECT semi‐quantitative chemiluminescent microparticle immunoassay was used to assess IgG antibodies to the nucleocapsid protein of SARS‐CoV‐2. Units with a S/C value ≥4.5 were considered high titer.ResultsA total of 232 CCP donations were evaluated. There were no significant differences in the distribution of sex, age, and interval from symptom resolution to donation by ABO blood group. The mean SARS‐CoV‐2 IgG antibody S/C value was significantly lower in blood group O donations (3.6), compared to blood group A (5.0) donations (p < .001). There was no difference in antibody response between the other blood group pairings. Blood group O donations resulted in a lower percentage of high‐titer units (35%), compared to blood group A (60%), B (58%), and AB (65%) donations.ConclusionBlood group O donations were found to have significantly lower levels of SARS‐CoV‐2 IgG nucleocapsid antibodies compared to blood group A donations and were less likely to produce CCP units that qualified as high titer. These findings may aid donor recruitment to promote availability of high‐titer CCP to meet patient needs.

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS‐CoV‐2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS‐CoV‐2 infection who underwent antibody testing with a single commercially available anti‐nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty‐six (51%) had positive anti‐nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti‐nucleocapsid antibodies, and transplant‐related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID‐19 may be less likely to form SARS‐CoV‐2 antibodies.

Differential Antibody Response against Conformational and Linear Epitopes of the L1 Proteins from Human Papillomavirus Types 16/18 Is Observed in Vaccinated Women or with Uterine Cervical Lesions.

Antibodies against the Human Papillomavirus (HPV) L1 protein are associated with past infections and related to the evolution of the disease, whereas antibodies against L1 Virus-Like Particles (VLPs) are used to follow the neutralizing antibody response in vaccinated women. In this study, serum antibodies against conformational (VLPs) and linear epitopes of HPV16/18 L1 protein were assessed to distinguish HPV-vaccinated women from those naturally infected or those with uterine cervical lesions. The VLPs-16/18 were generated in baculovirus, and L1 proteins were obtained from denatured VLPs. Serum antibodies against VLPs and L1 proteins were evaluated by ELISA. The ELISA-VLPs and ELISA-L1 16/18 assays were validated with a vaccinated women group by ROC analysis and the regression analysis to distinguish the different populations of female patients. The anti-VLPs-16/18 and anti-L1-16/18 antibodies effectively detect vaccinated women (AUC = 1.0/0.79, and 0.94/0.84, respectively). The regression analysis showed that anti-VLPs-16/18 and anti-L1-16/18 antibodies were associated with the vaccinated group (OR = 2.11 × 108/16.50 and 536.0/49.2, respectively). However, only the anti-L1-16 antibodies were associated with the high-grade lesions and cervical cancer (CIN3/CC) group (OR = 12.18). In conclusion, our results suggest that anti-VLPs-16/18 antibodies are effective and type-specific to detect HPV-vaccinated women, but anti-L1-16 antibodies better differentiate the CIN3/CC group. However, a larger population study is needed to validate these results.

Age-specific effects of vaccine egg adaptation and immune priming on A(H3N2) antibody responses following influenza vaccination.

A(H3N2) influenza vaccine effectiveness (VE) was low during the 2016-19 seasons and varied by age. We analyzed neutralizing antibody responses to egg- and cell-propagated A(H3N2) vaccine and circulating viruses following vaccination in 375 individuals (aged 7 months to 82 years) across all vaccine-eligible age groups in 3 influenza seasons. Antibody responses to cell- versus egg-propagated vaccine viruses were significantly reduced due to the egg-adapted changes T160K, D225G, and L194P in the vaccine hemagglutinins. Vaccine egg adaptation had a differential impact on antibody responses across the different age groups. Immunologically naive children immunized with egg-adapted vaccines mostly mounted antibodies targeting egg-adapted epitopes, whereas those previously primed with infection produced broader responses even when vaccinated with egg-based vaccines. In the elderly, repeated boosts of vaccine egg-adapted epitopes significantly reduced antibody responses to the WT cell-grown viruses. Analysis with reverse genetic viruses suggested that the response to each egg-adapted substitution varied by age. No differences in antibody responses were observed between male and female vaccinees. Here, the combination of age-specific responses to vaccine egg-adapted substitutions, diverse host immune priming histories, and virus antigenic drift affected antibody responses following vaccination and may have led to the low and variable VE against A(H3N2) viruses across different age groups.

MRNA SARS-CoV-2 Immunization Confers Robust Antibody Response in Occupational Healthcare Workers and Fosters Workplace Safety.

mRNA SARS-CoV-2 Immunization Confers Robust Antibody Response in Occupational Healthcare Workers and Fosters Workplace Safety.

A peptide-based assay discriminates individual antibody response to SARS-CoV-2

SARS-CoV-2 virus is responsible for the current worldwide coronavirus disease 2019 (COVID-19) pandemic, infecting millions of people and causing hundreds of thousands of deaths. Understanding the antibody response to SARS-CoV-2 is crucial for the development of vaccines, therapeutics and public health interventions. However, lack of consistency in methods used to monitor antibody response to SARS-CoV-2 leaves some uncertainty in our fine understanding of the human antibody response mounted following SARS-CoV-2 infection. We developed a peptide-based enzyme-linked immunosorbent assay (ELISA) by selecting 7 synthetic peptides from the spike, membrane, and nucleocapsid protein sequences of SARS-CoV-2, which effectively detects the antibody response mounted by all COVID-19 convalescent tested. Strikingly, the assay shows a profound difference in antibody response among individual subjects, which may have a significant impact on disease severity. Together, our results define an efficient and specific serological assay to consistently measure the antibody response following SARS-CoV-2 infection, as well as help the design of vaccine and therapeuticals for prevention and treatment of COVID-19.

Immunogenicity and safety of different dose schedules and antigen doses of an MF59-adjuvanted H7N9 vaccine in healthy adults aged 65 years and older

BackgroundThe number of human influenza A (H7N9) infections has escalated since 2013 with high resultant mortality. We conducted a phase II, randomized, partially-blinded trial to evaluate the safety and immunogenicity of an MF59-adjuvanted inactivated, split virion, H7N9 influenza vaccine (H7N9 IIV) administered at various dose levels and schedules in older adults. Methods479 adults ≥ 65 years of age in stable health were randomized to one of six groups to receive either 3.75, 7.5 or 15 µg of influenza A/Shanghai/02/2013 (H7N9) IIV adjuvanted with MF59 given as a 3-dose series either on days 1, 28 and 168 or on days 1, 57 and 168. Immunogenicity was assessed using both hemagglutination inhibition (HAI) and microneutralization (MN) assays prior to and 28 days following each dose. Safety was assessed through 1 year following the last dose. ResultsSubjects in all groups had only modest immune responses, with the HAI GMT < 20 after the second vaccine dose and <29 after the third vaccine dose. HAI titers ≥ 40 were seen in <37% of subjects after the second dose and <49% after the third dose. There were no significant differences seen between the two dose schedules. MN titers followed similar patterns, although the titers were approximately two-fold higher than the HAI titers. Logistic regression modeling demonstrated no statistically significant associations between the immune responses and age, sex or body mass index whereas recent prior receipt of seasonal influenza vaccine significantly reduced the HAI response [OR 0.13 (95% CI 0.05, 0.33); p < 0.001]. Overall, the vaccine was well tolerated. Two mild potentially immune mediated adverse events occurred, lichen planus and guttate psoriasis. ConclusionsMF59-adjuvanted H7N9 IIV was only modestly immunogenic in the older adult population following three doses. There were no significant differences in antibody responses noted among the various antigen doses or the two dose schedules.

Antibody Responses After Oxford Astrazeneca (Covishield) Vaccine Among Healthcare Workers in Dhaka Medical College, Dhaka, Bangladesh

Background: Oxford AstraZeneca (Covishield) vaccine is the 1st vaccine administered in Bangladesh to prevent the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the antibody response after 1st and 2nd dose of this vaccine in health care workers of Dhaka Medical College hospital, Bangladesh.Methods: Health care workers (teachers, clinicians and medical staff) of Dhaka Medical College Hospital who participated in this study were asked to collect blood sample after 28 days of 1st vaccination and 14 days after 2nd vaccination. Quantitative post-vaccination antibody responses were measured using the chemiluminescent immunoassay, ADVIA Centaur (Siemens, Munich, Germany) SARS-CoV-2 IgG (COV2G) assay (output index was ≥1·00).Findings: Among 308 participants 197(64%) were male and 111(36%) were female. The mean age was 45·08 years (±9·2 years). 35·06% participants were previously COVID-19 positive confirmed by RT- PCR. Vaccine related antibody was found in 126(41%) participants after 1st dose of AstraZeneca vaccine. After 2nd dose of vaccine reactive level of antibody was found in 172(93%) participants. Antibody responses were significantly higher in previously infected participants compared to participants who had no history of previous COVID-19 after1st dose (51·92±50·85 vs 23·67±41·07, p=0·001) as well as 2nd dose of vaccine (64·12±97·76 vs 35·04±64·84, p=0·001). No difference in antibody response was observed among participants with or without comorbidities.Interpretation: Oxford AstraZeneca Covishield vaccine induces a strong immune response after two doses of vaccination.Funding Information: The study was funded by the office of Directorate General of Health Services, Ministry of Health and Family Welfare, Bangladesh.Declaration of Interests: We wish to confirm that there are no known conflicts of interest associated with this publication.Ethics Approval Statement: All the participants provided written informed consent and the protocol was approved by ethical review committee of Dhaka Medical College.

Loci Associated With Antibody Response in Feral Swine (Sus scrofa) Infected With Brucella suis.

Feral swine (Sus scrofa) are a destructive invasive species widespread throughout the United States that disrupt ecosystems, damage crops, and carry pathogens of concern for the health of domestic stock and humans including Brucella suis—the causative organism for swine brucellosis. In domestic swine, brucellosis results in reproductive failure due to abortions and infertility. Contact with infected feral swine poses spillover risks to domestic pigs as well as humans, companion animals, wildlife, and other livestock. Genetic factors influence the outcome of infectious diseases; therefore, genome wide association studies (GWAS) of differential immune responses among feral swine can provide an understanding of disease dynamics and inform management to prevent the spillover of brucellosis from feral swine to domestic pigs. We sought to identify loci associated with differential antibody responses among feral swine naturally infected with B. suis using a case-control GWAS. Tissue, serum, and genotype data (68,516 bi-allelic single nucleotide polymorphisms) collected from 47 feral swine were analyzed in this study. The 47 feral swine were culture positive for Brucella spp. Of these 47, 16 were antibody positive (cases) whereas 31 were antibody negative (controls). Single-locus GWAS were performed using efficient mixed-model association eXpedited (EMMAX) methodology with three genetic models: additive, dominant, and recessive. Eight loci associated with seroconversion were identified on chromosome 4, 8, 9, 10, 12, and 18. Subsequent bioinformatic analyses revealed nine putative candidate genes related to immune function, most notably phagocytosis and induction of an inflammatory response. Identified loci and putative candidate genes may play an important role in host immune responses to B. suis infection, characterized by a detectable bacterial presence yet a differential antibody response. Given that antibody tests are used to evaluate brucellosis infection in domestic pigs and for disease surveillance in invasive feral swine, additional studies are needed to fully understand the genetic component of the response to B. suis infection and to more effectively translate estimates of Brucella spp. antibody prevalence among feral swine to disease control management action.

Breast Implants and Immune Modulation: Does Foreign Body-Induced Inflammation Promote Immunosurveillance of Breast Tumor Antigen?

BACKGROUND: Women with cosmetic breast implants have significantly lower rates of subsequent breast cancer than the general population.1 We hypothesize breast implant-induced local inflammation stimulates immunosurveillance recognition of breast tumor antigen. METHODS: Women with breast-related complaints were recruited from the plastic surgery clinic. Sera was collected and tested via ELISA assay for antibody responses to common breast tumor antigens: BRCA2, CEA, HER-2, mammaglobin-A and MUC-1, as well as tetanus. A cohort of patients had sera collected prospectively to allow comparison of pre- and postimplant placement. Antibody response levels between long-term breast implant (LTBI) and implant-naive (IN) groups were compared with unpaired t test. Antibody responses pre- and postimplant placement were compared with paired t test. Statistical analysis was performed with Graphpad Prism v8.0.2. RESULTS: One hundred four women were recruited. Thirty-six (34.6%) had LTBI, whereas 68 (65.4%) were IN. Women with LTBI had higher antibody responses than those with IN to mammaglobin-A (OD450, 0.33 versus 0.22; P = 0.003) and MUC-1 (OD450, 0.42 versus 0.34; P = 0.02). There was no difference in antibody responses to BRCA2, CEA, HER-2, or tetanus. In the sample of patients with longitudinal sera samples pre- and postoperative, antibody responses postimplant placement were significantly increased to mammaglobin-A (mean difference 0.13, P = 0.0002) and MUC-1 (mean difference 0.08, P = 0.02). There was no difference in postimplant responses to BRCA2, CEA, HER-2, or tetanus. There was no difference in antibody responses between women with or without capsular contracture, with or without rupture, with or without surface texture, or with subglandular versus submuscular placement. CONCLUSION: Women with LTBI have higher antibody recognition of breast tumor-associated antigens mammaglobin-A and MUC1. This study provides the first evidence of implant-related immune responses to breast cancer antigens. REFERENCE: 1. Noels EC, Lapid O, Lindeman JHN, et al. Breast implants and the risk of breast cancer: a meta-analysis of cohort studies. Aesthetic Surg J. 2015;35:55–62.

Differential antibody responses to Giardia lamblia strain variants expressing dissimilar levels of an immunogenic protein.

Giardia lamblia is a protozoan parasite that causes giardiasis, one of the most common worldwide gastrointestinal diseases. For rational development of a Giardia vaccine, increasing our understanding of the host-Giardia interaction is crucial. In this study, we analysed the immunogenicity and antigenicity of two G lamblia strain variants [GS and GS-5G8 (+)], which express different levels of the variant-specific surface protein (VSP) 5G8 and also analysed the intestinal histological changes associated with Giardia infection. We evaluated the antibody responses induced by G lamblia strains in infected, reinfected and immunized C3H/HeJ mice using ELISA, flow cytometry, Western blotting and histological analysis. Our results showed that G lamblia GS-5G8 (+) was more immunogenic and antigenic than the GS strain. The antibody response against the GS-5G8 (+) strain primarily recognized 5G8 protein. Serum antibody from infected and reinfected mice exhibited specific agglutination of trophozoites in vitro. GS-5G8 (+)-infected mice showed higher CD19+ infiltrating cell levels compared to GS-infected animals. G lamblia strains with different expression levels of an immunogenic antigen (VSP 5G8) induce differential antibody responses. A better understanding of the immunogenic proteins of G lamblia will contribute to the rational development of an effective vaccine against this parasitic disease.

Associations between geographic region and immune response variations to pneumococcal conjugate vaccines in clinical trials: A systematic review and meta-analysis

ObjectiveGeographic region can be an important source of variation in the immune response to pneumococcal conjugate vaccines (PCV). The aim of this study was to collate data from available PCV clinical trials in order to characterize the differences in antibody responses in different countries. MethodsA systematic review and meta-analysis was conducted to examine the difference in antibody responses after primary series of PCVs in infants, associated with geographic regions, compared with each other and with the different PCVs using random-effects models. ResultsA total of 69 trials were included. Studies conducted in the Western Pacific Region (WPR) showed higher geometric mean concentrations (GMC) compared to studies conducted in Europe. The pooled GMC for serotype 4 after three doses of PCV7 in the WPR was 5.19 μg/ml (95% confidence interval 4.85–5.53 μg/ml), while for studies conducted in Europe this was 2.01 μg/ml (95% confidence interval 1.88–2.14 μg/ml). The IgG GMC ratios among the WPR versus European regions ranged from 1.51 to 2.87 for PCV7, 1.69 to 3.22 for PCV10, and 1.49 to 3.08 for PCV13. ConclusionsStudies conducted in the WPR generally showed greater antibody responses than the studies conducted in Europe. Indications of differences among geographic regions highlight the fact that further research is needed to compare the biological factors contributing to immune responses, which may affect vaccination schedules.

Differences in Antibody Responses against Chelonid Alphaherpesvirus 5 (ChHV5) Suggest Differences in Virus Biology in ChHV5-Seropositive Green Turtles from Hawaii and ChHV5-Seropositive Green Turtles from Florida.

Fibropapillomatosis (FP) is a tumor disease associated with a herpesvirus (chelonid herpesvirus 5 [ChHV5]) that affects mainly green turtles globally. Understanding the epidemiology of FP has been hampered by a lack of robust serological assays to monitor exposure to ChHV5. This is due in part to an inability to efficiently culture the virus in vitro for neutralization assays. Here, we expressed two glycoproteins (FUS4 and FUS8) from ChHV5 using baculovirus. These proteins were immobilized on enzyme-linked immunosorbent assay plates in their native form and assayed for reactivity to two types of antibodies, full-length 7S IgY and 5.7S IgY, which has a truncated Fc region. Turtles from Florida were uniformly seropositive to ChHV5 regardless of tumor status. In contrast, in turtles from Hawaii, we detected strong antibody reactivity mainly in tumored animals, with a lower antibody response being seen in nontumored animals, including those from areas where FP is enzootic. Turtles from Hawaii actively shedding ChHV5 were more seropositive than nonshedders. In trying to account for differences in the serological responses to ChHV5 between green turtles from Hawaii and green turtles from Florida, we rejected the cross-reactivity of antibodies to other herpesviruses, differences in viral epitopes, or differences in procedure as likely explanations. Rather, behavioral or other differences between green turtles from Hawaii and green turtles from Florida might have led to the emergence of biologically different viral strains. While the strains from turtles in Florida apparently spread independently of tumors, the transmission of the Hawaiian subtype relies heavily on tumor formation.IMPORTANCE Fibropapillomatosis (FP) is a tumor disease associated with chelonid herpesvirus 5 (ChHV5) that is an important cause of mortality in threatened green turtles globally. FP is expanding in Florida and the Caribbean but declining in Hawaii. We show that Hawaiian turtles mount antibodies to ChHV5 mainly in response to tumors, which are the only sites of viral replication, whereas tumored and nontumored Floridian turtles are uniformly seropositive. Tumor viruses that depend on tumors for replication and spread are rare, with the only example being the retrovirus causing walleye dermal sarcoma in fish. The Hawaiian strain of ChHV5 may be the first DNA virus with such an unusual life history. Our findings, along with the fundamental differences in the life histories between Floridian turtles and Hawaiian turtles, may partly explain the differential dynamics of FP between the two regions.

Antibody response to homologous epitopes of Epstein-Barr virus, Mycobacterium avium subsp. paratuberculosis and IRF5 in patients with different connective tissue diseases and in mouse model of antigen-induced arthritis

BackgroundImproved knowledge of different biomarkers is crucial for early diagnosis of rheumatic diseases and to provide important insights for clinical management. In this study, we evaluated the seroreactivity of patients with different connective tissue diseases (CTDs) (rheumatoid arthritis, RA; systemic lupus erythematosus, SLE; systemic sclerosis, SSc; and Sjogren’s syndrome, SSj) to interferon regulatory factor 5 (IRF5) peptide and homologs derived from Epstein-Barr virus (EBV) and Mycobacterium avium subsp. paratuberculosis (MAP). Antigen-induced arthritis (AIA) experiments have been performed in control and IRF5 conditional knockout mice to reinforce the hypothesis that antibodies generated against the three homologous peptides are cross-reactive. MethodsReactivity against wild-type (wt) and citrullinated (cit) IRF5 (IRF5424-434), MAP (MAP_402718-32) and EBV (BOLF1305-320) peptides were tested by indirect ELISA in sera from 100 RA patients, 54 patients with other CTDs (14 SLE, 28 SSc and 12 SSj) and 100 healthy subjects (HCs). Antibody responses to the same wt peptides have been tested in AIA mouse sera after immunization with complete Freud’s adjuvant (CFA) and methylated bovine serum albumin (mBSA) to induce arthritis in the knee joint. ResultsBOLF1, MAP_4027 and IRF5 peptides triggered different antibody responses in CTD diseases with a stronger reactivity in RA (p=0.0001). Similar trends were observed in AIA mice with significantly higher reactivity after 7 days from induction of arthritis. We also found statistically significant differences in antibody responses between SSc and HCs for BOLF1 (p=0.003), MAP_4027 (p=0.0076) and IRF5 (p=0.0042). Peripheral reactivity to cit peptides was lower compared to their wt counterparts, except for cit-MAP_402718-32, which induced stronger responses in RA than wt-MAP_402718-32 (46% vs. 26%, p=0.0170).Conclusion(s): Our results show differential antibody responses to BOLF1, MAP_4027 and IRF5 peptides among CTDs, highlighting their potential as diagnostic biomarkers in these diseases. Experiments performed in IRF5 conditional knockout mice support the hypothesis of cross-reactivity between the investigated homologous antigens.

LEVELS OF H. PYLORI ANTIBODIES AND INFLAMMATORY MARKERS IN BLOOD SERUM SAMPLES OF MOSCOW RESIDENTS

Introduction. Helicobacter pylori (Hр) is considered usually as one of the factors in the development of gastritis, peptic ulcer, and gastric cancer, and at the same time as protection from asthma, diabetes type II, and obesity. This study was carried out with a goal to evaluate possible linkage between the levels of circulating anti-Hp antibodies and inflammatory markers - IL-6, IL-8 and malonic dialdehyde (MDA) - in cross-sectional study of Moscow adults. Material and Methods. Serum samples of Moscow working-aged residents (both gender, N=252) were used for evaluation of antibodies to lysate Hp antigen/recombinant CagA and cytokines IL-6, IL-8 with corresponding ELISA kits. MDA was determined by reaction with thiobarbituric acid. Results. Standard correlation analysis didn’t reveal any significant association between the levels of circulating antibodies against the applied commercial antigens and the levels of IL-6, IL-8 and MDA. Nevertheless, two parallel branches of the experimental points in seropositive area of anti-CagA/IL-8 scatterplot (but not for IL-6 and MDA variables) were clearly seen and correspond to two maximums at bimodal anti-CagA distribution. The data obtained are consistent with typical for CagA outstrip in IL-8 induction and testify the existence of two human genotypes having ~2-fold difference in antibody response but the same reactivity of CagA - IL-8 axis. Since CagA-positive IL-8 levels are of one order with CagA-negative ones (from another organs) and signs of concomitant oxidative stress were not revealed, the data obtained can be interpreted equally as early pathologic or actual symbiotic events. Conclusion. Quantitative assessment of circulating anti-Hp antibodies, together with more detail mathematical analysis, will increase contributions of population studies to investigation of equilibrium between Hp and human organisms.