Persistence Of Antibodies Research Articles

Rubella antibodies in vertically and horizontally HIV-infected young adults vaccinated early in life and response to a booster dose in those with seronegative results

BackgroundVery limited data are available on the persistence of rubella antibodies in vertically HIV-infected individuals who were vaccinated early in life. MethodsProspective, cohort study on 4 groups of patients: 96 vertically HIV-1-infected individuals (v-HIV), 69 horizontally HIV-1-infected individuals (h-HIV), 93 healthy controls previously vaccinated for rubella (vac-CON) and 20 healthy controls with history of rubella disease (dis-CON). A blood sample was collected and rubella antibodies were analyzed by ELISA. Rubella antibodies above 10 IU/mL were considered protective. Individuals with seronegative results were offered an extra MMR vaccine dose and were tested at least 30 days afterwards. ResultsTime since previous rubella vaccination was similar in v-HIV, h-HIV and vac-CON (16, 11 and 11 years; p = 0.428). v-HIV and h-HIV were also comparable regarding median CD4 T cells (613 and 614 cells/mm3; p = 0.599) and percentage on ART (93.8% and 98.6%; p = 0.135) at study entry. v-HIV had less individuals on virological suppression (63.5%) compared to 85.5% in h-HIV (p < 0.001). Rubella seropositivity and antibodies were significantly lower in v-HIV compared to h-HIV (32.3% vs 65.5%, 4.3 IU/mL vs 21.1 IU/mL; p < 0.001). Time interval between the last rubella vaccine dose and study entry was associated with an increase of rubella seronegativity, with a 7% higher chance of seronegativity for each one-year increase. After an extra MMR dose, 40 out of 48 (83.3%) seronegative individuals responded, with no significant difference among groups considering rubella seropositivity and antibody levels. ConclusionAs vertically HIV-infected individuals reach adolescence and adulthood, assessment of vaccine antibodies can identify those who might benefit from an extra vaccine dose.

#11 Development of a Kinetic ELISA (kELISA) and Reactive B Cell Frequency (RBF) Assay to Detect Respiratory Syncytial Virus (RSV) Pre-Fusion F Protein-Specific Immune Responses in Infants

Abstract Background RSV is a major cause of pediatric respiratory disease. Antibodies to the prefusion conformation of the RSV fusion (pre-F) protein are needed for virus neutralization. Method We measured RSV-specific responses in two groups of children &amp;lt;3 years of age; subjects with laboratory-confirmed RSV (RSV-infected) or infants born in the period May to September and enrolled prior to their first RSV season (RSV-uninfected). RSV-infected infants had blood samples obtained at 1, 6, 9, and 12 months after infection. RSV-uninfected infants had blood samples obtained at enrollment, at the end of their first RSV season, and 6 months later. A kELISA to measure RSV pre-F-specific antibodies and an RBF assay to identify RSV F-specific B cells were developed. Results 102 subjects were enrolled; 11 were excluded due to missed visits or withdrawal. Of the 65 subjects in the RSV-uninfected group, all were kELISA positive at enrollment, consistent with maternal antibody transfer. 53 subjects had sufficient samples for analysis at multiple time points; 29 became seronegative and 24 remained seropositive. In the seronegative group, the kELISA value decreased rapidly to &amp;lt;0.25 by 6 months after the RSV season in 27/29 (93%), (Figure 1a). In the persistently seropositive group, all 24 subjects maintained a positive kELISA value, with some developing higher values over time, consistent with asymptomatic infection (Figure 1b). An RBF assay was used to determine whether antibodies were due to persistent maternal antibodies or endogenous production (Figure 1c). In the seronegative group, 24/29 (80%) had a negative RBF; in the seropositive group, 23/24 (96%) had a positive RBF during follow-up. There were 26 subjects in the RSV-infected group; 22 had sufficient samples for analysis at multiple time points. All were seropositive by kELISA at one month post-infection with variable kELISA values during follow-up (Figure 1d). 17/22 (77%) had a positive RBF, although 4 of the subjects without a positive RBF had indeterminate results at ≥ 1 visit. Conclusion Assays measuring F-specific immune responses in infants will be critical for RSV vaccine development. A kELISA targeting RSV pre-F epitopes, with an RBF assay targeting RSV F-specific B cells, may allow discrimination for maternal and infant-derived antibodies.

Estimating the duration of antibody positivity and likely time of Leptospira infection using data from a cross-sectional serological study in Fiji.

Leptospirosis is a zoonotic disease prevalent throughout the world, but with particularly high burden in Oceania (including the Pacific Island Countries and Territories). Leptospirosis is endemic in Fiji, with outbreaks often occurring following heavy rainfall and flooding. As a result of non-specific clinical manifestation and diagnostic challenges, cases are often misdiagnosed or under-ascertained. Furthermore, little is known about the duration of persistence of antibodies to leptospirosis, which has important clinical and epidemiological implications. Using the results from a serosurvey conducted in Fiji in 2013, we fitted serocatalytic models to estimate the duration of antibody positivity and the force of infection (FOI, the rate at which susceptible individuals acquire infection or seroconversion), whilst accounting for seroreversion. Additionally, we estimated the most likely timing of infection. Using the reverse catalytic model, we estimated the duration of antibody persistence to be 8.33 years (4.76-12.50; assuming constant FOI) and 7.25 years (3.36-11.36; assuming time-varying FOI), which is longer than previous estimates. Using population age-structured seroprevalence data alone, we were not able to distinguish between these two models. However, by bringing in additional longitudinal data on antibody kinetics we were able to estimate the most likely time of infection, lending support to the time-varying FOI model. We found that most individuals who were antibody-positive in the 2013 serosurvey were likely to have been infected within the previous two years, and this finding is consistent with surveillance data showing high numbers of cases reported in 2012 and 2013. This is the first study to use serocatalytic models to estimate the FOI and seroreversion rate for Leptospira infection. As well as providing an estimate for the duration of antibody positivity, we also present a novel method to estimate the most likely time of infection from seroprevalence data. These approaches can allow for richer, longitudinal information to be inferred from cross-sectional studies, and could be applied to other endemic diseases where antibody waning occurs.

Clinical characteristics and prognosis of patients with antiphospholipid antibodies based on cluster analysis: an 8-year cohort study

BackgroundAntiphospholipid syndrome (APS) is an autoimmune disease characterized by persistent antiphospholipid antibodies (aPLs) positivity with a wide manifestation spectrum. A risk stratification is needed for management guidance and prognosis assessment. We aimed to identify phenotypes among aPL-positive patients and assess the prognosis of each phenotype.MethodsThis was a single-center, prospective cohort study of aPL-positive patients presented to Peking Union Medical College Hospital from 2012 to 2020. Demographic characteristics, aPL-related manifestations, cardiovascular risk factors, and antibodies profiles were recorded. The primary endpoint was defined as a combination of newly onset thrombosis, major bleeding events, non-criteria manifestations, and all-cause death. Hierarchical cluster analysis and Kaplan-Meier survival analysis were performed.ResultsFour clusters among 383 patients (70.2% female; mean age 37.7 years) were identified. Cluster 1 (n = 138): patients with systemic lupus erythematosus (SLE) and non-criteria manifestations; cluster 2 (n = 112): patients with multiple cardiovascular risk factors; cluster 3 (n = 83): female patients with obstetric morbidity; cluster 4 (n = 50): patients with isolated lupus anticoagulant (LA) positivity.Non-criteria manifestations were found aggregated with SLE from cluster analysis of variables. Cluster 3 showed the best outcome, while cluster 2 suffered highest frenquency of newly onset arterial thrombosis.ConclusionsWe identified 4 clinical phenotypes of aPL-positive patients. Non-criteria manifestations may indicate underlying SLE, for which immunosuppressive therapy besides anticoagulation may be necessary. Patients with isolated LA positivity suffered similar risks with secondary APS and patients with multiple cardiovascular risk factors. Attention should be paid to male patients, and the screening of cardiovascular risk factors should never be ignored.

Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history

BackgroundThe continuous emergence of SARS-CoV-2 variants of concern (VOC) with immune escape properties, such as Delta (B.1.617.2) and Omicron (B.1.1.529), questions the extent of the antibody-mediated protection against the virus. Here we investigated the long-term antibody persistence in previously infected subjects and the extent of the antibody-mediated protection against B.1, B.1.617.2 and BA.1 variants in unvaccinated subjects previously infected, vaccinated naïve and vaccinated previously infected subjects.MethodsBlood samples collected 15 months post-infection from unvaccinated (n=35) and vaccinated (n=41) previously infected subjects (Vo’ cohort) were tested for the presence of antibodies against the SARS-CoV-2 spike (S) and nucleocapsid (N) antigens using the Abbott, DiaSorin, and Roche immunoassays. The serum neutralising reactivity was assessed against B.1, B.1.617.2 (Delta), and BA.1 (Omicron) SARS-CoV-2 strains through micro-neutralisation. The antibody titres were compared to those from previous timepoints, performed at 2- and 9-months post-infection on the same individuals. Two groups of naïve subjects were used as controls, one from the same cohort (unvaccinated n=29 and vaccinated n=20) and a group of vaccinated naïve healthcare workers (n=61).ResultsWe report on the results of the third serosurvey run in the Vo’ cohort. With respect to the 9-month time point, antibodies against the S antigen significantly decreased (P=0.0063) among unvaccinated subjects and increased (P<0.0001) in vaccinated individuals, whereas those against the N antigen decreased in the whole cohort. When compared with control groups (naïve Vo’ inhabitants and naïve healthcare workers), vaccinated subjects that were previously infected had higher antibody levels (P<0.0001) than vaccinated naïve subjects. Two doses of vaccine elicited stronger anti-S antibody response than natural infection (P<0.0001). Finally, the neutralising reactivity of sera against B.1.617.2 and BA.1 was 4-fold and 16-fold lower than the reactivity observed against the original B.1 strain.ConclusionsThese results confirm that vaccination induces strong antibody response in most individuals, and even stronger in previously infected subjects. Neutralising reactivity elicited by natural infection followed by vaccination is increasingly weakened by the recent emergence of VOCs. While immunity is not completely compromised, a change in vaccine development may be required going forward, to generate cross-protective pan-coronavirus immunity in the global population.

Biodegradable Imiquimod-Loaded Mesoporous Organosilica as a Nanocarrier and Adjuvant for Enhanced and Prolonged Immunity against Foot-and-Mouth Disease Virus in Mice.

Foot-and-mouth disease (FMD), a serious, fast-spreading, and virulent disease, has led to huge economic losses to people all over the world. Vaccines are the most effective way to control FMD. However, the weak immunogenicity of inactivated FMD virus (FMDV) requires the addition of adjuvants to enhance the immune effectiveness of the vaccines. Herein, we formulated and fabricated biodegradable dendritic mesoporous tetrasulfide-doped organosilica nanoparticles SOMSN with imiquimod complex (SOMSN-IMQ) and used it as a platform for FMD vaccine delivery and as an adjuvant. SOMSN-IMQ demonstrated excellent stability for 6 months when stored in PBS, while it could be completely degraded within 42 days in SBF at room temperature. Biosafety experiments such as cell toxicity, hemolysis, and histology indicated that the as-prepared SOMSN-IMQ showed nontoxicity and good biocompatibility. Furthermore, SOMSN-IMQ exhibited a maximum adsorption capacity of 1000 μg/mg for inactivated FMDV antigens. Our results showed that SOMSN-IMQ can be effectively engulfed by RAW264.7 cells in a dose-dependent manner. After immunization, SOMSN-IMQ@FMDV can elicit persistent higher antibody levels, higher IgG2a/IgG1 ratio, and cytokine expression, which indicated that SOMSN-IMQ@FMDV triggered superior humoral and cellular immune responses. Moreover, SOMSN-IMQ could provoke maturation and activation of dendritic cells in lymph nodes (LDCs) as well as the proliferation of lymphocytes in vivo. Thus, SOMSN-IMQ could promote effective and potent immunity and provide a promising adjuvant platform for FMDV vaccination with acceptable safety.

Middle East Respiratory Syndrome Coronavirus Infection Elicits Long-lasting Specific Antibody, T and B Cell Immune Responses in Recovered Individuals.

BackgroundThe Middle East respiratory syndrome coronavirus (MERS-CoV) is a highly pathogenic zoonotic betacoronavirus and a global public health concern. Better undersetting of the immune responses to MERS-CoV is needed to characterize the correlates of protection and durability of the immunity and to aid in developing preventative and therapeutic interventions. Although MERS-CoV–specific circulating antibodies could persist for several years post-recovery, their waning raises concerns about their durability and role in protection. Nonetheless, memory B and T cells could provide long-lasting protective immunity despite the serum antibodies levels.MethodsSerological and flow cytometric analysis of MERS-CoV–specific immune responses were performed on samples collected from a cohort of recovered individuals who required intensive care unit (ICU) admission as well as hospital or home isolation several years after infection to characterize the longevity and quality of humoral and cellular immune responses.ResultsOur data showed that MERS-CoV infection could elicit robust long-lasting virus-specific binding and neutralizing antibodies as well as T- and B-cell responses up to 6.9 years postinfection regardless of disease severity or need for ICU admission. Apart from the persistent high antibody titers, this response was characterized by B-cell subsets with antibody-independent functions as demonstrated by their ability to produce tumor necrosis factor α (TNF-α), interleukin (IL)-6, and interferon γ (IFN-γ) cytokines in response to antigen stimulation. Furthermore, virus-specific activation of memory CD8+ and CD4+ T cell subsets from MERS-recovered patients resulted in secretion of high levels of TNF-α, IL-17, and IFN-γ.ConclusionsMERS-CoV infection could elicit robust long-lasting virus-specific humoral and cellular responses.

Impact of ChAdOx1 nCoV-19 (Covishield™) Vaccination: How Long Will It Persist?

An increase in COVID-19 immunization coverage has been linked to a decrease in the average case fatality rate. As a result, further research is needed to determine the persistence and duration of vaccine-induced protective antibodies in order to assess the effectiveness of COVID-19 vaccinations. The present study aimed to determine the COVID-19 IgG antibodies among healthcare workers (HCWs) before and after the ChAdOx1 nCoV-19 (Covishield™) vaccination. A total of 150 HCWs who had received the Covishield™ vaccine were assessed after obtaining written informed consent. Blood samples were drawn at three time points, namely, within one week prior to first dose of vaccination, prior to second dose of vaccination (28–33 days after the first dose of vaccination), and 90–95 days after the second dose of vaccination for detecting neutralizing antibodies, i.e., IgG antibodies by ELISA. The overall baseline seropositivity among the HCWs was found to be 28% (n = 42), assessed by the sample collected prior to first dose of COVID-19 vaccination. The seroconversion rate was reported to be 80% (n = 120) one month after the first dosage and increased to 92.7% (n = 139) three months later. Additionally, there was a significant gradual increase in the IgG concentrations postvaccination in majority of the study participants. In those HCWs who had prior history of SARS-CoV-2 infection, significantly higher antibody level was observed compared to antibody-naive individuals. Fever, pain or swelling at the site of injection, and headache were the most frequently reported adverse events following vaccination among the study participants. Regardless of prior SARS-CoV-2 positivity, two doses of the CovishieldTM vaccine elicited a protective neutralizing antibody response that lasted for three months after the second dose of vaccination.

Anticardiolipin IgA as a Potential Risk Factor for Pregnancy Morbidity in Patients with Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS) is an autoimmune disorder that is characterized by venous or arterial thrombosis and/or obstetric morbidity in the constant presence of persistent antiphospholipid antibodies (aPLs). In patients with APS, the relationship between production of immunoglobulin (Ig)A antiphospholipid antibodies and adverse events in pregnancy is still unclear. As a result of massive trials, the clinical efficiency of IgA-aPLs is used to evaluate pregnancy outcomes in patients with APS. We enrolled 381 female patients with APS and 93 healthy pregnant women. Silica clotting time ratio, dilute Russell viper venom time (dRVVT) ratio, and 6 aPLs, including IgA/IgG/IgM isotypes aβ2GPI and IgA/IgG/IgM isotypes anticardiolipin (aCL), were detected using commercial kits. We found no significant differences in laboratory parameters between patients with APS and the control group. The total prevalence of aCL IgA was 2.9%; the prevalence of aβ2GPI IgA was 3.4%. Only 1.3% of the individuals who tested aCL-positive (5/381) had isolated aCL IgA. Similarly, isolated aβ2GPI IgA was present in only 0.8% (3/381) of the aβ2GPI-positive subjects. Meanwhile, aCL IgA showed the maximum area under the curve (AUC) of 0.666 (95% CI, 0.60-0.73; P < .001), followed by dRVVT ratio (AUC = 0.649; 0.58-0.72; P < .001). Positive aCL IgA and aβ2GPI IgA ratios were extremely low for each isolated isotype of aPLs. For patients with APS who experienced fetal loss, aCL IgA may be utilized as a risk factor for pregnancy loss among patients with APS. Establishing a standardized diagnosis of IgA aPLs is also important for these patients.

Quantitative and Qualitative Difference in Antibody Response against Omicron and Ancestral SARS-CoV-2 after Third and Fourth Vaccination.

Waning immunity against SARS-CoV-2 and the emergence of variants, especially of the most distant variant, Omicron, affect titers of neutralizing antibodies in the sera of vaccinated individuals. Thus, two vaccinations with the mRNA vaccine BNT162b fail to induce neutralizing antibodies against the Omicron variant. A first booster vaccination increases Omicron-RBD-binding IgG and IgA and neutralizing capacity. In comparison, the Wuhan isolate titers of the Omicron variant binding antibodies are 8.5 lower. After a third vaccination, induction of Omicron-RBD- and Wuhan-RBD-binding antibodies follows the same kinetic. Five to six months after the third vaccination, there are still Omicron-RBD-binding antibodies detectable, but 35.9 percent of the analyzed sera fail to neutralize the Omicron variant, while all sera efficiently neutralize the Delta isolate. In the case of the Wuhan-RBD, a significantly larger number of stable antigen–antibody complexes is formed than in Omicron-RBD. A fourth vaccination with mRNA-1273 temporarily restores levels of Omicron-, Delta- and Wuhan-specific antibodies. Comparing different booster strategies revealed that the breadth of the immune response is not affected by the vaccination regimen. Taken together, these data indicate that booster vaccinations (third and fourth dose) increase the breadth of the immune response, but there is a qualitative difference of antibodies with respect to the stability of antigen–antibody complexes and persistence of antibody titers.

Durability and Immunogenicity of Neutralizing Antibodies Response Against Omicron Variants After Three Doses of Subunit SARS-CoV-2 Vaccine MVC-COV1901: An Extension to an Open-Label, Dose-Escalation Phase1 Study.

IntroductionMVC-COV1901 is a protein subunit COVID-19 vaccine based on the stable prefusion spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide. Interim results of a phase 2 clinical trial demonstrated favorable safety profile and immunogenicity and the vaccine has been authorized for use in Taiwan. However, waning antibody levels after immunization and variants of concern (VoC) could negatively impact vaccine-induced neutralization of virus. In this extension to the phase 1 clinical study we investigated a three-dose regimen of MVC-COV1901 for durability of antibody levels and virus neutralization capacity, including neutralization of the Omicron variant.MethodsForty-five healthy adults from 20 to 49 years of age were divided into three groups of 15 participants receiving two doses of either low dose (LD), medium dose (MD), or high dose (HD) of MVC-COV1901. Six months after the second dose (day 209), a third MD dose of MVC-COV1901 was administered to the LD and MD groups and a HD dose was given to the HD group. Safety was followed for up to 28 days after the booster dose by monitoring incidences of adverse events (AE). Immunogenicity and antibody persistence for up to 6 months after the booster dose were assessed by neutralizing assay with the wild-type (Wuhan) SARS-CoV-2 virus. To examine the immunogenicity of booster dose against variants, neutralizing assays were carried out with the Alpha, Beta, and Delta variant viruses and the Omicron variant pseudovirus using samples from 4 weeks after the booster dose.ResultsAdverse reactions after the booster dose were mostly mild and comparable to that of the first two doses. Compared to day 209, neutralizing antibodies were increased by 10.3–28.9 times at 4 weeks after the booster. During the 6-month follow-up after the booster, the rate of decline of neutralizing antibody level was much less than that after the second dose. Three doses of MVC-COV1901 also improved antibody-mediated neutralization of Alpha, Beta, and Delta variants as well as the Omicron variant pseudovirus.ConclusionOur data showed increased persistence of neutralizing antibodies and enhancement of immunogenicity against VoCs offered after a third dose of MVC-COV1901.Trial RegistrationClinicalTrials.gov identifier NCT04487210.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40121-022-00652-6.

Malaria transmission structure in the Peruvian Amazon through antibody signatures to Plasmodium vivax.

BackgroundThe landscape of malaria transmission in the Peruvian Amazon is temporally and spatially heterogeneous, presenting different micro-geographies with particular epidemiologies. Most cases are asymptomatic and escape routine malaria surveillance based on light microscopy (LM). Following the implementation of control programs in this region, new approaches to stratify transmission and direct efforts at an individual and community level are needed. Antibody responses to serological exposure markers (SEM) to Plasmodium vivax have proven diagnostic performance to identify people exposed in the previous 9 months.MethodologyWe measured antibody responses against 8 SEM to identify recently exposed people and determine the transmission dynamics of P. vivax in peri-urban (Iquitos) and riverine (Mazán) communities of Loreto, communities that have seen significant recent reductions in malaria transmission. Socio-demographic, geo-reference, LM and qPCR diagnosis data were collected from two cross-sectional surveys. Spatial and multilevel analyses were implemented to describe the distribution of seropositive cases and the risk factors associated with exposure to P. vivax.Principal findingsLow local transmission was detected by qPCR in both Iquitos (5.3%) and Mazán (2.7%); however, seroprevalence indicated a higher level of (past) exposure to P. vivax in Mazán (56.5%) than Iquitos (38.2%). Age and being male were factors associated with high odds of being seropositive in both sites. Higher antibody levels were found in individuals >15 years old. The persistence of long-lived antibodies in these individuals could overestimate the detection of recent exposure. Antibody levels in younger populations (<15 years old) could be a better indicator of recent exposure to P. vivax.ConclusionsThe large number of current and past infections detected by SEMs allows for detailed local epidemiological analyses, in contrast to data from qPCR prevalence surveys which did not produce statistically significant associations. Serological surveillance will be increasingly important in the Peruvian Amazon as malaria transmission is reduced by continued control and elimination efforts.

Presence of SARS-CoV-2 antibodies following COVID-19 diagnosis: a longitudinal study of patients at a major urgent care provider in New York

The duration of antibody persistence following natural infection is unclear. We examined routine SARS-CoV-2 diagnostic and serological testing data on 6522 persons diagnosed between March 2020 and March 2021 who had at least 1 antibody test ≥30 days after diagnosis at CityMD, an urgent care provider. Using survival analysis, we estimated the median duration of detectable anti-SARS-CoV-2 antibodies and hazard of seroreversion by demographic and clinical characteristics. We found that over 90% (95% CI: 91.8%, 94.8%) of the study population had detectable levels of antibodies at 180 days post diagnosis and that SARS-CoV-2 antibodies persisted at a detectable level for a median duration of 342 days following infection (95% CI: 328, 361). Additionally, there were differences in antibody persistence by age, with older patients less likely to serorevert compared to younger patients. These findings suggest that protection from natural infection may wane with time and differ by demographic factors.

MO919: Persistence of Antibodies After SARS-COV-2 Vaccines in Haemodialysis Patients: A 6 Months Follow-Up

BACKGROUND AND AIMSAs COVID-19 related mortality is higher in haemodialysis patients than in the general population, proper vaccination strategies against the SARS-CoV-2 virus have utmost importance. It has been previously shown that mRNA vaccines (e.g. BNT162b2) can generate >95% of seropositivity in haemodialysis patients [1]. On the other hand, the seropositivity rate reached by the inactivated vaccine (CoronaVac®) was around 80%. In this study, we aimed to analyse the persistence of SARS-CoV-2 antibodies in haemodialysis patients for 6 months and compare it with the healthy controls.METHODHaemodialysis patients who were vaccinated either by BNT162b2 or CoronaVac® and who continued their regular controls for 6 months were involved in the study. Those who had previous or active SARS-CoV-2 infection, who had malignancies and those who had received immunosuppressive drugs in the previous 12 month were excluded from the study. SARS-CoV-2 IgG levels were measured by a commercial test after the first doses of the vaccines and at the end of the sixth month. Healthy healthcare workers who were vaccinated with similar vaccine schemes were taken as the control group.RESULTSWe recruited 85 haemodialysis patients who had received their first doses of either vaccine. Of them, 4 patients died; 3 patients were hospitalized because of COVID-19 infection during the follow-up; 9 patients missed at least one of their regular controls; and 2 patients were diagnosed with malignancy. A total of 26 patients experienced asymptomatic or mild COVID-19 infection during the follow-up period. SARS-CoV-2 IgG levels were measured at the end of the sixth month for the remaining 41 patients. Sero-positivity significantly decreased at the end of the sixth month for both vaccines, but the BNT162b2 group (n = 22) still had better seropositivity than CoronaVac® (n = 19) group (81% versus 50%; P = .03). In contrast, the seropositivity of healthy controls, even with the inactivated vaccine, was 96%. When one booster dose was applied, 90% of seropositivity could be maintained in the BNT162b2 group at the sixth month.CONCLUSIONBNT162b2 vaccine generates more persistent antibodies than inactivated vaccines in haemodialysis patients. However, when compared with the healthy controls at the end of the sixth month, antibody titers decrease more profoundly in haemodialysis patients. The booster dose can maintain the antibody levels and should be applied at least every 6 months.

Outcomes of HPV type-specific serostatus do not associate with oral or genital HPV-carriage in non-vaccinated women followed for three years

BackgroundThe role of human papillomavirus (HPV) antibodies acquired through natural infection and their role in protection for subsequent cervical or oral HPV-carriage remains unclear.MethodsA total of 267 women, with a 36-months follow-up, from the Finnish Family HPV (FFHPV) study were evaluated to shed more light on persistent HPV-specific antibodies to genital or oral HPV-carriage, clearance or persistence during the three years follow-up. The type-specific seroprevalence for HPV genotypes 6, 11, 16, 18 and 45 in these women was assessed in relation to the detection of the same genotype or any HPV in their oral and genital samples. The following HPV serological outcomes where detected: being always seronegative, seroconversion or persistent seropositivity.ResultsGenital HPV16 infections were most prevalent at the end of the follow-up (24- and 36-month visit) among women who tested always seronegative for HPV16. No such associations between serology and HPV detection were established for the other HPV genotypes in the genital or oral samples. The development of long-term type-specific HPV 6,11,16,18 and 45 persistence (≥ 24 months) or clearance of the genital or oral infections was not different among the women with high HPV genotype specific antibody levels and those testing always HPV-seronegative.ConclusionNo significant role was disclosed for the acquired natural high-level- or persistent HPV antibodies as determinants of the genital or oral HPV infection outcomes in these young, non-vaccinated women.

Status of Humoral and Cellular Immune Responses within 12 Months following CoronaVac Vaccination against COVID-19.

ABSTRACTUnderstanding immune memory to COVID-19 vaccines is critical for the design and optimal vaccination schedule for curbing the COVID-19 pandemic. Here, we assessed the status of humoral and cellular immune responses at 1, 3, 6, and 12 months after two-dose CoronaVac vaccination. A total of 150 participants were enrolled, and 136 of them completed the study through the 12-month endpoint. Our results show that, at 1 month after vaccination, both binding and neutralizing antibodies could be detected; the seropositive rate of binding antibodies and seroconversion rate of neutralizing antibodies were 99% and 50%, respectively. From 3 to 12 months, the binding and neutralizing antibodies declined over time. At 12 months, the binding and neutralizing antibodies were still detectable and significantly higher than the baseline. Gamma interferon (IFN-γ) and interleukin 2 (IL-2) secretion specifically induced by the receptor-binding domain (RBD) persisted at high levels until 6 months and could be observed at 12 months, while the levels of IL-5 and granzyme B (GzmB) were hardly detected, demonstrating a Th1-biased response. In addition, specific CD4+ T central memory (TCM), CD4+ effector memory (TEM), CD8+ TEM, and CD8+ terminal effector (TE) cells were all detectable and functional up to 12 months after the second dose, as the cells produced IFN-γ, IL-2, and GzmB in response to stimulation of SARS-CoV-2 RBD. Our work provides evidence that CoronaVac induced not only detectable binding and neutralizing antibody responses, but also functional SARS-CoV-2-specific CD4+ and CD8+ memory T cells for up to 12 months.

Evaluation of Natural and Vaccine-Induced Anti-SARS-CoV-2 Immunity: A Comparative Study between Different Groups of Volunteers.

(1) Background: The production of anti-SARS-CoV-2 antibodies should help minimize the severity of COVID-19 disease. Our focus was to investigate and compare different vaccination schedules, monitoring circulating S-RBD Ab (antibodies anti—Spike protein—Receptor Binding Domain) levels after administering two doses in naïve patients. Likewise, vaccine-stimulated immunity in naïve and previously infected patients was compared. (2) Methods: We included 392 patients. Sera were evaluated by Elecsys anti-SARS-CoV-2 S. Statistical analyses were conducted by MedCalc and JASP. (3) Results: In COVID-19 patients, the median value of Ab levels was 154 BAU/mL, stable up to 9 months after the infection. From the data observed in vaccinated patients, higher median values were recorded in COVID-19/Pfizer BioNTech (18913 BAU/mL) than in other groups (Pfizer BioNTech: 1841; ChadOx1 961; heterologous vaccination: 2687) BAU/mL. (4) Conclusions: In conclusion, a single booster dose given to previously infected patients raised an antibody response much higher than two doses given to naïve individuals and heterologous vaccination generated a robust persistent antibody response at high levels, steady up to three months after administration.

Immunogenicity and safety of the 9-valent human papillomavirus vaccine in Chinese females 9–45 years of age: A phase 3 open-label study

BackgroundThe 9-valent human papillomavirus (9vHPV; HPV6/11/16/18/31/33/45/52/58) vaccine was approved for use in Chinese women aged 16–26 years in 2018. This phase 3, open-label study (NCT03903562) compared 9vHPV vaccine immunogenicity and safety in Chinese females aged 9–19 years and 27–45 years with Chinese females aged 20–26 years; we report results from day 1 through 1 month post-Dose 3. The study will continue through 54 months post-Dose 3 to assess antibody persistence in Chinese girls aged 9–19 years. MethodsParticipants aged 9–45 years received three doses of the 9vHPV vaccine. Geometric mean titers (GMTs) and seroconversion percentages for anti-HPV6/11/16/18/31/33/45/52/58 antibodies were determined by competitive Luminex immunoassay in serum samples obtained at day 1 and 1 month post-Dose 3. Adverse events (AEs) within 30 days post-vaccination and serious AEs (SAEs) occurring at any time were recorded. ResultsIn total, 1990 participants (690 aged 9–19 years; 650 aged 20–26 years; 650 aged 27–45 years) were enrolled. At 1 month post-Dose 3, >99% of participants in the per-protocol immunogenicity population seroconverted to each vaccine HPV type. Anti-HPV6/11/16/18/31/33/45/52/58 antibody GMTs in the 9–19-year age group were non-inferior to those in participants aged 20–26 years. Anti-HPV6/11/16/18/31/33/45/52/58 seroconversion percentages in the 27–45-year age group were non-inferior to those in participants aged 20–26 years. Injection-site and systemic AEs were reported by 43.3% and 50.9%, 50.5% and 57.1%, and 43.8% and 43.4% of participants aged 9–19, 20–26, and 27–45 years, respectively. There were no vaccine-related SAEs, discontinuations due to AEs, and deaths. ConclusionAntibody responses induced by 9vHPV vaccination in Chinese females aged 9–19 years and 27–45 years were non-inferior to those in Chinese females aged 20–26 years. The vaccine was generally well tolerated.ClinicalTrials.gov Identifier: NCT03903562.

Long Term Follow up of Patients With Primary Obstetric Antiphospholipid Syndrome.

Introduction: Primary obstetric antiphospholipid syndrome (OAPS) is defined by specific morbidities and/or losses of pregnancy in the presence of persistent antiphospholipid antibodies (aPL). This variant of APS is usually treated during pregnancy and the post-partum period. Data on occurrence of thrombotic event during long term follow-up of OAPS patients is limited. Methods: A multi-centre retrospectively cohort of female patients with primary APS (pAPS) was assembled during 2004–2019. Patients were grouped according to disease presentation as pure OAPS or thrombotic APS (tAPS) for those presenting with thrombosis. Clinical and serological data were compared between groups. Results: Of 219 pAPS female patients 67 (30.6%) were diagnosed with OAPS and 152 (69.4%) with tAPS. During >10 years of follow-up 24/67 (35.8%) OAPS and 71/152 (50%) tAPS suffered a new thrombotic event (p = 0.06), while obstetric morbidity was more likely in the OAPS group (31.3 vs. 10.5%, p < 0.001) respectively. Among patients with OAPS at presentation heart valve disease and the presence of ANA were related to thrombosis following diagnosis (25 vs. 4.7%, p = 0.02; and 45.8 vs. 20.8%, p = 0.04 respectively). Conclusion: Thrombotic event following diagnosis were common among female patients with pAPS regardless of disease presentation. Heart valve disease and ANA positivity may be risk factors for thrombosis during follow-up of patients presenting with pure OAPS.

Identification of B-cell dominant epitopes in the recombinant protein P29 from Echinococcus granulosus.

Introduction Echinococcus granulosus (E. granulosus) causes a hazardous zoonotic parasitic disease. This parasite can occupy the liver and several areas of the body, causing incurable damage. Our previous studies have provided evidence that the recombinant protein P29 (rEg.P29) exhibit immune protection in sheep and mice against pathological damage induced by E. granulosus, showing its potential as candidate for vaccine development. However, information on the B‐cell epitopes of rEg.P29 has not yet been reported.MethodsImmunological model was established in mice with rEg.P29. SDS‐PAGE and Western blot were used to identify protein. Screening for B‐cell dominant epitope peptides of rEg.P29 by enzyme‐linked immunosorbent assay (ELISA) and immune serum. Dominant epitopes were validated using ELISA and flow cytometry. Multiple sequence alignment analysis was performed using BLAST and UniProt.ResultsImmunization with rEg.P29 induced intense and persistent antibody responses, and the epitope of the dominant antigen of B cells are identified as rEg.P29 166–185 (LKNAKTAEQKAKWEAEVRKD). Anti‐rEg.P29 166–185‐specific antibodies lack epitopes against IgA, IgE, and IgG3, compared to anti‐rEg.P29‐specific antibodies. However, anti‐rEg.P29 166–185 IgG showed comparatively higher titers, as determined among those peptides by endpoint titration. In addition, rEg.P29 and rEg.P29 166–185 promote B‐cell activation and proliferation in vitro. The dominant epitopes are relatively conserved in different subtypes of the rEg.P29 sequence.Conclusion rEg.P29 166–185 can act as a dominant B‐cell epitope for rEg.P29 and promote cell activation and proliferation in the same way as rEg.P29.