Persistence Of Antibodies Research Articles

Enhanced D614G and Omicron Variants Antibody Persistence in Infants at 2 Months of Age Following Maternal mRNA Booster Vaccination During Pregnancy or Postpartum

Background: Following maternal COVID-19 vaccination, the persistence of antibodies in sera and breast milk for mothers and infants is not well characterized. We sought to describe the persistence of antibodies through 2 months after delivery in maternal and infant serum and breast milk following maternal COVID-19 mRNA vaccination and to examine differences by receipt of booster dose during pregnancy or postpartum. Methods: This is a prospective cohort study with enrollment from July 2021 to January 2022 at 9 US academic sites. Pregnant or postpartum participants and their infants were enrolled after COVID-19 mRNA monovalent vaccination during pregnancy (primary 2-dose series) with booster (third dose) vaccination during pregnancy or within 2 months post-partum. SARS-CoV-2–binding and functional antibody responses at delivery and 2 months after delivery in mothers and infants were measured by spike and receptor-binding domain immunoglobulin (Ig) G, pseudovirus and live neutralizing antibody (nAb) titers to ancestral and Omicron BA.1 and BA.5 strains. Breast milk spike and receptor-binding domain IgG and IgA titers were also measured. Results: A total of 237 maternal/infant dyads were included (110 primary series during pregnancy, 99 pregnancy booster and 28 postpartum booster). A pregnancy booster resulted in 2.2-4.7-fold higher IgG and nAb at delivery and 2 months for both mothers and infants compared to the primary series alone (P < 0.001 for all comparisons). While infant IgG and nAb titers decreased by 2 months of age, the proportion of infants with detectable nAb at 2 months was greater in infants of mothers boosted during pregnancy compared with primary series for all variants (D614G: 99% vs. 56%; BA.1: 56% vs. 4% and BA.5: 57% vs. 9%; P < 0.001 for all comparisons). Breast milk spike IgA and IgG were present in 64%-100% and 100% of participants, respectively, and those boosted during pregnancy or postpartum had 3.1-4.6-fold higher levels of breast milk antibodies at 2 months compared to primary series during pregnancy (P < 0.001). Conclusions: mRNA COVID-19 monovalent booster vaccination during pregnancy results in significantly higher maternal and infant serum–binding IgG and nAb titers compared to a primary 2-dose series, including against Omicron variants, through 2 months of age. Breast milk antibodies following maternal vaccination during pregnancy or postpartum may provide additional protection during early infancy.

Antibody persistence and safety of a live-attenuated chikungunya virus vaccine up to 2 years after single-dose administration in adults in the USA: a single-arm, multicentre, phase 3b study

Chikungunya virus infection can lead to long-term debilitating symptoms. A precursor phase 3 clinical study showed high seroprotection (defined as a 50% plaque reduction of chikungunya virus-specific neutralising antibodies on a micro plaque reduction neutralisation test [μPRNT] titre of ≥150 in baseline seronegative participants) up to 6 months after a single vaccination of the chikungunya virus vaccine VLA1553 (Valneva Austria, Vienna, Austria) and a good safety profile. Here we report antibody persistence and safety up to 2 years. In this single-arm, multicentre, phase 3b study, we recruited participants from the precursor phase 3 trial from professional vaccine trial sites in the USA. Participants (aged ≥18 years) were eligible if they had completed the previous study and received VLA1553. Chikungunya virus-specific neutralising antibodies were evaluated at 28 days, 6 months, and 1 year and 2 years after vaccination. The primary outcome was the proportion of seroprotected participants (ie, μPRNT50 titre of ≥150) at 1 and 2 years, assessed in all eligible participants who had at least one post-vaccination immunogenicity sample available, overall and by age group at the time of vaccination (18-64 years and ≥65 years). Adverse events of special interest at the time of transition from the previous study to the current study (ie, at 6 months) and serious adverse events during the current study were recorded (ie, between 6 months and 2 years). All analyses were descriptive. This study is registered with ClinicalTrials.gov, NCT04838444, and immunogenicity follow-up is ongoing. In the precursor study, participants were screened between Sept 17, 2020, and April 10, 2021; data cutoff for this analysis was March 31, 2023. Of 2724 participants in the precursor study who received one dose of VLA1553, 363 participants were analysed in this study (310 [85%] aged 18-64 years and 53 [15%] aged ≥65 years at enrolment in the precursor study; mean age 47·7 years [SD 14·2], 207 [57%] of 363 participants were female, 156 [43%] were male, 280 [77%] were White, and 314 [87%] were not Hispanic or Latino). Strong seroprotection was observed at 1 year (98·9% [356 of 360 assessable participants; 97·2-99·7]) and 2 years (96·8% [306 of 316; 94·3-98·5]) after vaccination, and was very similar between those aged 18-64 years (at 1 year: 98·7% [303 of 307; 96·7-99·6]; at 2 years: 96·6% [256 of 265; 93·7-98·4]) and those aged 65 years and older (at 1 year: 100% [53 of 53; 93·3-100]; at 2 years: 98·0% [50 of 51; 89·6-100]) at each timepoint. No adverse events of special interest were ongoing at the time of transition. Ten serious adverse events occurred in nine (2%) participants between the 6-month and 2-year timepoints, including one death (due to drug overdose) that was determined to not be related to VLA1553. After a single VLA1553 vaccination, chikungunya virus-neutralising antibodies above the threshold considered to be protective persisted up to 2 years and there were no long-term serious adverse events related to vaccination. VLA1553 is an efficient and safe intervention that offers high seroprotection against chikungunya virus infection, a virus likely to spread globally with an urgent demand for long-lasting prophylaxis. Valneva Austria, Coalition for Epidemic Preparedness Innovation, and EU Horizon 2020.

Persistence of maternal antibodies against goat pox virus in goat kids.

In goat kids, choosing the appropriate age to administer the first dose of goat pox disease (GTP) vaccine requires knowing when maternal antibody decline concentrations. Determine the persistence of maternal antibodies against goat pox virus (GTPV) in goat kids. Twenty Saanen goat kids from birth to 120 days old. In 2 groups, including: control (receiving colostrum from nonvaccinated does) and treatment (receiving colostrum from vaccinated does). On zero, 3, 7, 14, 21, 28, 42, 56, 70, 100 and 120 days after the birth, virus neutralization test was used to measure the serum concentration of antibodies against GTPV. At the age of 56 days, the first seronegative goat kids (n = 2) were recorded in the treatment group. At the age of 120 days, all the goat kids in the treatment group were seronegative. The average virus neutralization index (VNI) of the goat kids became negative at the age of 100 to 120 days. All goat kids in the control group were negative at all times. One hundred to 120 days of the age seems to be the time to administer the first GTP vaccine in the goat kids with passive immunity against goat pox.

Comparison of anti-phospholipid antibody titers before and after SARS-CoV-2 mRNA vaccination in hospital staff

Multiple concerning reports have emerged of cardiovascular complications, particularly thrombosis, following mRNA vaccination against the SARS-CoV-2 pathogen. The presence of serologically persistent anti-phospholipid antibodies is a characteristic of antiphospholipid syndrome, which presents with clinical manifestations including thrombosis or pregnancy morbidity. Anti-SARS-CoV-2 mRNA vaccines pose a theoretical risk of cross-reactivity between the SARS-CoV-2 spike protein and phospholipids in host tissues. In this study, serum anti-phospholipid antibody titers before and after SARS-CoV-2 mRNA vaccination were compared among 184 hospital staff members. Although no significant differences were found in terms of antibody titers targeting cardiolipin and β2-glycoprotein I, post-vaccination antibody titers targeting phosphatidylethanolamine were found to be significantly increased compared to pre-vaccination levels (p = 0.008). Anti-phosphatidylethanolamine antibodies are the most common anti-phospholipid antibodies detected in patients with recurrent miscarriages at < 10 weeks of gestation. However, the association between vaccination and these types of adverse events remains unknown, thus warranting further investigation.

The Impact of Smoking on Long-Term Protection Following Hepatitis B Vaccination: A 24-Year Cohort Study.

The hepatitis B vaccination-induced immune response has been demonstrated to be associated with a number of factors, including age, sex, BMI, and the presence of comorbidities. Additionally, modifiable determinants such as smoking have been identified as influencing the response to vaccination. However, despite the evidence that smokers are at an increased risk of not responding to vaccination, the long-term effects of smoking on antibody persistence remain poorly understood. This study aims to assess the impact of smoking habits on long-term immunity following the primary vaccination cycle. Participants were required to have received a standard three-dose vaccine schedule in childhood, without subsequent doses, and to be between 18 and 24 years of age. Data on age, sex, BMI, age of administration of the first vaccine dose, and time between doses were collected. An antibody concentration < 10 IU/L was considered as non-protective. A total of 2133 individuals were included, 14.2% of whom were smokers. The mean age was 20.28 ± 0.92 years. The probability of having a non-protective antibody concentration was significantly higher in smokers than in non-smokers (AOR: 1.287; 95% CI: 1.002-1.652). The detrimental effects of smoking extend beyond the immediate effects on the vaccine response, also impairing the long-term immune response in individuals who received vaccinations during childhood.

Persistence of Antibodies against Measles, Mumps, and Rubella after the Two-Dose MMR Vaccination: A 7-Year Follow-Up Study.

In 2014, the Expanded Program on Immunization of Thailand changed the timing of the second dose of the measles-mumps-rubella (MMR) vaccine from 4-6 years to 2.5 years, while maintaining the first dose at 9 months of age. This study aimed to examine the dynamics and durability of immune responses induced by the two-dose MMR vaccine in a group of 169 Thai children from 4 to 7 years of age (4.5 years after the second MMR dose). We followed a cohort of healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) where they were administered either the Priorix vaccine (GlaxoSmithKline Biologicals, Rixensart, Belgium) or M-M-RII (Merck & Co., Kenilworth, NJ, USA) at 9 months and 2.5 years of age. Blood samples were collected annually from ages 4 to 7 years. Anti-measles, -mumps, and -rubella IgG levels were evaluated using the enzyme-linked immunosorbent assay (EUROIMMUN, Lubeck, Germany). A total of 169 children completed this study. Over the 4.5 years following the two-dose MMR vaccination, we observed a decline in the seroprotection rates against measles and mumps, but not rubella. Longitudinal monitoring of antibody persistence, among other strategies, will help predict population-level immunity and inform public health interventions to address potential future outbreaks.

Investigation of the Seroprevalence of Brucella Antibodies and Characterization of Field Strains in Immunized Dairy Cows by B. abortus A19.

(1) Background: One method of eradicating brucellosis is to cull cattle that test positive for antibodies 12 months after being vaccinated with the 19-strain vaccine. Variations in immunization regimens and feeding practices may contribute to differences in the rate of persistent antibodies. We conducted this study to investigate the real positive rate of Brucella antibody in field strains of Brucella spp. after immunization over 12 months in dairy cows. This research aims to provide data to support the development of strategies for preventing, controlling, and eradicating brucellosis. (2) Method: We employed the baseline sampling method to collect samples from cows immunized with the A19 vaccine for over 12 months in Lingwu City from 2021 to 2023. Serological detection was conducted using the RBPT method. An established PCR method that could distinguish between 19 and non-19 strains of Brucella was utilized to investigate the field strains of Brucella on 10 dairy farms based on six samples mixed into one using the Mathematical Expectation strategy. (3) Results: We analyzed the rates of individual seropositivity and herd seropositive rates in dairy cattle in Lingwu City from 2021 to 2023 and revealed that antibodies induced by the Brucella abortus strain A19 vaccine persist in dairy herds for more than 12 months. We established a PCR method for identifying both Brucella A19 and non-A19 strains, resulting in the detection of 10 field strains of Brucella abortus from 1537 dairy cows. By employing a Mathematical Expectation strategy, we completed testing of 1537 samples after conducting only 306 tests, thereby reducing the workload by 80.1%. (4) Conclusions: There was a certain proportion of cows with a persistent antibody titer, but there was no evidence that all of these cattle were naturally infected with Brucella. The established PCR method for distinguishing between Brucella abortus strain 19 and non-19 strains can be specifically utilized for detecting natural Brucella infection in immunized cattle. We propose that relying solely on the detection of antibodies in cattle immunized with the A19 vaccine more than 12 months previously should not be solely relied upon as a diagnostic basis for brucellosis, and it is essential to complement this approach with PCR analysis to specifically identify field Brucella spp. Brucella abortus was the predominant strain identified in the field during this study. Detection based on the Mathematical Expectation strategy can significantly enhance detection efficiency.

Antibody persistence 7 years after hepatitis-A vaccine in children with human immunodeficiency virus infection

Antibody persistence 7 years after hepatitis-A vaccine in children with human immunodeficiency virus infection

Positive Outcome in a Pregnancy with Anti-kell Alloimmunization Treated with Intravenous Immunglobulin and Therapeutic Plasma Exchange Despite Persistence of High Titre Antibody: A Case Report

Background: Few reports have been published about the current clinical management of anti-Kell alloimmunization in pregnancy; its low frequency of occurrence means that the few long series published have covered an extensive time period in which different treatment approaches have overlapped. The objective of the present paper is to present our experience in the clinical management of a pregnant woman who was positive for the anti-Kell antibody. Materials and Methods: The laboratory follow-up included the weekly measurement of the antibody titre, and identification of the paternal and fetal genotype. The clinical management included TPE and IVIG administration. Obstetric monitoring included ultrasonographic monitoring of the fetus. Case Description: We report a case of anti-Kell alloimmunization with high antibody titre at first observation. Testing for fetal DNA circulating in maternal blood confirmed positivity for KEL1 gene. The patient underwent fifteen sessions of TPE after 18 weeks of gestational age, followed by weekly IVIG infusion, which continued until 27 weeks of pregnancy. Anti-Kell titres were measured before and after each TPE session. The patient had no need for IUBT and delivered by cesarean section at 34 weeks of gestational age. Pregnancy resulted in a live birth with mild HDFN. Discussion: HDFN is a potentially lethal complication of alloimmunization, and IUBT is the standard treatment for severe fetal anemia. TPE and IVIG are two alternative treatment modalities described in the literature to avoid or postpone the need for IUBT transfusion. In the case reported, despite any substantial change in antibody titre, pregnancy resulted in a live birth. This result suggests that the use of TPE and IVIG in alloimmunization during pregnancy could be an effective treatment strategy.

A novel approach to induce early remission in high-risk primary membranous nephropathy.

This prospective single-arm trial with historic controls evaluated the efficacy and safety of treatment based on a combination of rituximab, intravenous cyclophosphamide, and corticosteroids (RCP) administered at lower cumulative doses for the induction of early remission in primary membranous nephropathy (PMN). We prospectively enrolled 30 high-risk PMN patients with persistent nephrotic syndrome (NS) and elevated antibodies to the phospholipase A2 receptor who underwent RCP therapy. We compared the effectiveness of RCP with that of historic controls who received rituximab-based therapy (RTX, n=15) or cyclosporine+corticosteroids (CSA, n=42). The primary outcomes were complete remission (CR) and overall remission (OR) by month 12 and the time to remission. In the RCP group, the OR and CR rates by 12 months (97% and 60%) were higher than those in the RTX group (60% and 7%, P≤0.009) and the CSA group (50% and 24%, P≤0.003). The median time to OR (2.8 (1.6-3.9) months) was shorter compared to RTX (7.1 (3.4-17.5) months, P=0.008) and CSA (7.3 (6.0-13.6) months, P<0.001). In adjusted Cox regression, hazard ratios for OR and CR attainment for RCP versus other treatments were 5.2 (95% CI: 2.8-9.6) and 4.8 (95% CI: 2.2-10.3), respectively. Propensity score-matched group analyses confirmed these results. One serious adverse event occurred in the RCP group in the follow-up of 56 patient-years. RCP therapy is considered effective and safe for inducing early remission in high-risk PMN patients.

Tracking the evolution of anti-SARS-CoV-2 antibodies and long-term humoral immunity within 2 years after COVID-19 infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that gave rise to COVID-19 infection produced a worldwide health crisis. The virus can cause a serious or even fatal disease. Comprehending the complex immunological responses triggered by SARS-CoV-2 infection is essential for identifying pivotal elements that shape the course of the disease and its enduring effects on immunity. The span and potency of antibody responses provide valuable perspicuity into the resilience of post-infection immunity. The analysis of existing literature reveals a diverse controversy, confining varying data about the persistence of particular antibodies as well as the multifaceted factors that impact their development and titer, Within this study we aimed to understand the dynamics of anti-SARS-CoV-2 antibodies against nucleocapsid (anti-SARS-CoV-2 (N)) and spike (anti-SARS-CoV-2 (N)) proteins in long-term immunity in convalescent patients, as well as the factors influencing the production and kinetics of those antibodies. We collected 6115 serum samples from 1611 convalescent patients at different post-infection intervals up to 21 months Study showed that in the fourth month, the anti-SARS-CoV-2 (N) exhibited their peak mean value, demonstrating a 79% increase compared to the initial month. Over the subsequent eight months, the peak value experienced a modest decline, maintaining a relatively elevated level by the end of study. Conversely, anti-SARS-CoV-2 (S) exhibited a consistent increase at each three-month interval over the 15-month period, culminating in a statistically significant peak mean value at the study’s conclusion. Our findings demonstrate evidence of sustained seropositivity rates for both anti-SARS-CoV-2 (N) and (S), as well as distinct dynamics in the long-term antibody responses, with anti-SARS-CoV-2 (N) levels displaying remarkable persistence and anti-SARS-CoV-2 (S) antibodies exhibiting a progressive incline.

Immunological Insights: A Multicenter Longitudinal Study on Humoral Response to COVID-19 Vaccines in Greece

Vaccination has emerged as the most effective tool in the battle against COVID-19. To optimize vaccination protocols, a deeper understanding of the immune response to vaccination, including influential factors and its duration, is essential. This study aimed to assess the humoral response in vaccinated individuals with or without prior SARS-CoV-2 infection. A prospective observational study was conducted across 14 private healthcare structures in Greece. Anti-spike IgG titers were measured at different timepoints following the initial vaccination and booster doses of the BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. A total of 505 participants were included in the first phase, evaluating the humoral response after the initial vaccination, and 311 participants were involved in the second phase, assessing the effects of booster vaccination. All vaccines elicited high anti-S IgG titers initially, followed by a subsequent decline that was addressed by the booster vaccination. The humoral response was sustained up to one year after the booster vaccination. mRNA vaccines induced higher anti-S IgG titers compared to vector vaccines, with mRNA-1273 eliciting higher titers than BNT162b2. Vaccination resulted in higher antibody titers than natural infection alone; however, convalescent patients who received vaccination had significantly higher anti-S IgG titers compared to those who received the booster vaccine without previous SARS-CoV-2 infection. Lower antibody titers were observed in men and older patients (&gt;51.5 years old), as well as smokers, although the decline rate was lower in these subgroups. These results underscore the importance of booster doses and reveal the potential influence of age, gender, smoking habits, and vaccine type on varying humoral responses. Long-term monitoring of antibody persistence, evaluation of cellular immune responses, and assessment of vaccine efficacy against emerging variants should be considered to enhance our understanding of immunity dynamics and inform vaccine development and deployment strategies.

Persistence and Efficacy of Maternal COVID-19 Vaccine-Induced Antibodies in Human Milk: A Comprehensive Meta-Analysis

Abstract Background: The ongoing global health challenge posed by the COVID-19 pandemic has necessitated a thorough examination of vaccine efficacy, particularly the transfer of vaccine-induced immunity to infants via human milk. This meta-analysis aims to explore the persistence and efficacy of COVID-19 vaccine-induced antibodies in human milk, offering insights into passive immunity transfer to breastfeeding infants. Methods: We conducted a systematic review and meta-analysis of peer-reviewed studies published from January 2021 to December 2023, extracted from databases such as PubMed, Scopus, and Web of Science. Our focus was on studies measuring SARS-CoV-2-specific antibodies (IgA and IgG) in human milk following maternal COVID-19 vaccination. Results: Fifteen studies involving 1,200 lactating mothers who received mRNA COVID-19 vaccines were included. The analysis highlighted a consistent presence of SARS-CoV-2-specific IgA and IgG antibodies in human milk, persisting for up to six months post-vaccination. Conclusion: The results highlight the noteworthy transmission of COVID-19 antibodies via human milk, suggesting an extended duration of possible protection for neonates against SARS-CoV-2 infection. This argues in favor of immunizing nursing mothers as a preemptive public health strategy to provide their children passive immunity.

#1658 Association of blood dd-cfDNA levels with Banff scores and histopathological lesions in kidney allograft biopsies: results from an observational trial

Abstract Background and Aims Donor-derived cell-free DNA (dd-cfDNA) is a novel blood biomarker of kidney allograft injury. While primarily studied to discriminate rejection from no rejection, knowledge about its dynamics in other graft pathologies is scarce and merits further investigation. Previous research has highlighted its superior diagnostic performance in detecting ABMR compared to TCMR and borderline changes, however, recent studies have suggested that its increase is not limited to damage due to alloimmune injury. Therefore, we aimed to assess the association between dd-cfDNA release and diverse histopathological patterns as well as its correlation with Banff lesion scores in renal allograft biopsies. Method For this analysis, we identified all dd-cfDNA-paired allograft biopsies from a prospective observational trial of kidney transplant recipients undergoing an indication biopsy with deterioration in graft function, persistence of anti-HLA donor-specific antibodies (DSA), or proteinuria. Dd-cfDNA was collected at the time of allograft biopsy and measured using droplet-digital PCR. Both relative and absolute quantification of dd-cfDNA, with cutoffs of 0.5% and 50cp/ml, respectively, were available for clinical interpretation. All biopsy specimens were examined by a central pathologist blinded to the dd-cfDNA results. Histopathological diagnoses were assigned according to the Banff 2019 classification. Results In total, we examined 125 dd-cfDNA paired biopsies from 110 patients performed at our center between April 2020 and October 2023. Absolute levels of dd-cfDNA were significantly higher in mixed rejection (median 156 cp/mL, IQR 138-176), antibody-mediated rejection (ABMR) (median 63cp/mL, IQR 48-81), DSA-negative microvascular inflammation (DSAnegMVI) (median 74 cp/mL, IQR 35-134), and BK-virus associated nephropathy (BKVAN) (median 168cp/mL, IQR 54-311) in comparison to glomerulonephritis (median 12cp/mL, IQR 8-19; p &amp;lt; 0.001, &amp;lt;0.001, 0.02, 0.01, respectively) as well as in comparison CNI-toxicity (median 10, IQR 6-15; p &amp;lt;0.001, &amp;lt;0.001, 0.004, 0.003, respectively). Additionally, patients with mixed rejection, ABMR, and BKVAN had higher absolute dd-cfDNA levels than patients with IFTA (median 13, IQR 8-16; p 0.004, 0.004, and 0.04, respectively), as well as normal histology (median 7, IQR 7-11, p 0.004, 0.008, 0.03, respectively). Finally, absolute dd-cfDNA levels were higher in patients with mixed rejection than in those with UTI (median 14, IQR 12-16, p = 0.02) (Fig. 1). In the univariable analysis, absolute dd-cfDNA levels were significantly correlated with Banff lesion scores for glomerulitis (g), peritubular capillaritis (ptc), and tubulitis (t). In the multivariable analysis, ptc and t were independently correlated with absolute dd-cfDNA levels. Conclusion Increased donor-derived cell-free DNA is not specific for rejection, but also occurs in alternative injury patterns showing microvascular inflammation and severe tubulointerstitial inflammation, such as DSAnegMVI and BKVAN (BK-virus associated nephropathy). Interestingly, dd-cfDNA levels remain low in the setting of de novo or recurrent glomerulonephritis and CNI-toxicity, which are important differential diagnoses in patients with clinical indication biopsy.

One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP—to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation—to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

Antibody persistence to diphtheria toxoid, tetanus toxoid, Bordetella pertussis antigens, and Haemophilus influenzae type b following primary and first booster with pentavalent versus hexavalent vaccines

ABSTRACT Thailand has incorporated the whole-cell (wP) pertussis vaccine into the expanded program on immunization since 1977 and has offered the acellular pertussis (aP) vaccine as an optional vaccine for infants since 2001. We followed healthy children from a clinical trial (ClinicalTrials.gov NCT02408926) in which children were randomly assigned to receive either pentavalent (DTwP-HB-Hib) or hexavalent (DTaP-IPV-HB-Hib) vaccines for their primary series (administered at 2, 4, and 6 months) and first booster vaccination (18 months). Both groups received Tdap-IPV as a second booster at the age of 4 y. Blood samples were collected for evaluation of antibody persistence to diphtheria toxoid (DT), tetanus toxoid (TT), and Bordetella pertussis (B. pertussis) between 2 and 6 y of age annually, and for the immunogenicity study of Tdap-IPV at 1 month after the second booster. Antibody persistence to Haemophilus influenzae type b (Hib) was followed until 3 y of age. A total of 105 hexavalent-vaccinated children and 91 pentavalent-vaccinated children completed this study. Both pentavalent and hexavalent groups demonstrated increased antibody levels against DT, TT, and B. pertussis antigens following the second booster with Tdap-IPV. All children achieved a seroprotective concentration for anti-DT and anti-TT IgG at 1 month post booster. The hexavalent group possessed significantly higher anti-pertactin IgG (adjusted p = .023), whereas the pentavalent group possessed significantly higher anti-pertussis toxin IgG (adjusted p < .001) after the second booster. Despite declining levels post-second booster, a greater number of children sustained protective levels of anti-DT and anti-TT IgG compared to those after the first booster.

CEA-CD3 bispecific antibody cibisatamab with or without atezolizumab in patients with CEA-positive solid tumours: results of two multi-institutional Phase 1 trials

Cibisatamab is a bispecific antibody-based construct targeting carcinoembryonic antigen (CEA) on tumour cells and CD3 epsilon chain as a T-cell engager. Here we evaluated cibisatamab for advanced CEA-positive solid tumours in two open-label Phase 1 dose-escalation and -expansion studies: as a single agent with or without obinutuzumab in S1 (NCT02324257) and with atezolizumab in S2 (NCT02650713). Primary endpoints were safety, dose finding, and pharmacokinetics in S1; safety and dose finding in S2. Secondary endpoints were anti-tumour activity (including overall response rate, ORR) and pharmacodynamics in S1; anti-tumour activity, pharmacodynamics and pharmacokinetics in S2. S1 and S2 enrolled a total of 149 and 228 patients, respectively. Grade ≥3 cibisatamab-related adverse events occurred in 36% of S1 and 49% of S2 patients. The ORR was 4% in S1 and 7% in S2. In S2, patients with microsatellite stable colorectal carcinoma (MSS-CRC) given flat doses of cibisatamab and atezolizumab demonstrated an ORR of 14%. In S1 and S2, 40% and 52% of patients, respectively, developed persistent anti-drug antibodies (ADAs). ADA appearance could be mitigated by obinutuzumab-pretreatment, with 8% of patients having persistent ADAs. Overall, cibisatamab warrants further exploration in immunotherapy combination strategies for MSS-CRC.

Impact of Transient and Persistent Donor-Specific Antibodies in Lung Transplantation.

Lung transplantation (LuTx) is an established treatment for patients with end-stage lung diseases, however, outcomes are limited by acute and chronic rejection. One aspect that has received increasing attention is the role of the host's humoral alloresponse, particularly the formation of de novo donor-specific antibodies (dnDSAs). The aim of this study was to investigate the clinical significance of transient and persistent dnDSAs and to understand their impact on outcomes after LuTx. A retrospective analysis was conducted using DSA screening data from LuTx recipients obtained at the Medical University of Vienna between February 2016 and March 2021. Of the 405 LuTx recipients analyzed, 205 patients developed dnDSA during the follow-up period. Among these, 167 (81%) had transient dnDSA and 38 (19%) persistent dnDSA. Persistent but not transient dnDSAs were associated with chronic lung allograft dysfunction (CLAD) and antibody-mediated rejection (AMR) (p < 0.001 and p = 0.006, respectively). CLAD-free survival rates for persistent dnDSAs at 1-, 3-, and 5-year post-transplantation were significantly lower than for transient dnDSAs (89%, 59%, 56% vs. 91%, 79%, 77%; p = 0.004). Temporal dynamics of dnDSAs after LuTx have a substantial effect on patient outcomes. This study underlines that the persistence of dnDSAs poses a significant risk to graft and patient survival.

The single-dose Janssen Ad26.COV2.S COVID-19 vaccine elicited robust and persistent anti-spike IgG antibody responses in a 12-month Ugandan cohort.

The study investigation examined the immune response to the Janssen Ad26.COV2.S COVID-19 vaccine within a Ugandan cohort, specifically targeting antibodies directed against spike (S) and nucleocapsid (N) proteins. We aimed to examine the durability and robustness of the induced antibody response while also assessing occurrences of breakthrough infections and previous anti-Spike seropositivity to SARS-CoV-2. The study included 319 specimens collected over 12 months from 60 vaccinees aged 18 to 64. Binding antibodies were quantified using a validated ELISA method to measure SARS-CoV-2-specific IgG, IgM, and IgA levels against the S and N proteins. The results showed that baseline seropositivity for S-IgG was high at 67%, increasing to 98% by day 14 and consistently stayed above 95% for up to 12 months. However, S-IgM responses remained suboptimal. A raised S-IgA seropositivity rate was seen that doubled from 40% at baseline to 86% just two weeks following the initial vaccine dose, indicating sustained and robust peripheral immunity. An increase in N-IgG levels at nine months post-vaccination suggested breakthrough infections in eight cases. Baseline cross-reactivity influenced spike-directed antibody responses, with individuals harbouring S-IgG antibodies showing notably higher responses. Robust and long lasting vaccine and infection-induced immune responses were observed, with significant implications for regions where administering subsequent doses poses logistical challenges.

Persistence of Treponema pallidum IgM antibodies in serum: What is their meaning?

We studied the detection of Treponema pallidum (TP)-IgM antibodies in the serum of 69 patients treated for syphilis. The persistence of TP-IgM antibodies in serum for more than 3 years was the only clue to suspect an active infection and, therefore, to investigate a central nervous system involvement.