Median Antibody Levels Research Articles

Heterologous Versus Homologous COVID-19 Boosters: Immune Response Outcomes in Renal Transplant Recipients.

We aimed to investigate the immune responses to homologous and heterologous COVID-19 booster vaccinations in renal transplant recipients (RTRs) and to identify factors affecting these responses. In this prospective multicenter observational study, we measured the antibody kinetics of 90 RTRs using the chemiluminescent microparticle immunoassay method. The mean age of participants was 45.2 ± 11.4 years, with 35.6% being female. On the 42nd day after the first vaccine dose, the median antibody level was 16.7 (IQR 2.5-249.5) AU/mL, and the seropositivity rate was 60% (n = 36). Mycophenolic acid (MFA) (OR: 0.087, 95% CI: 0.024-0.311) and ACE inhibitor use (OR: 0.203, 95% CI: 0.052-0.794) were identified as independent factors affecting seropositivity. Patients who received the Pfizer/BioNTech booster had significantly higher antibody levels compared to those who received the CoronaVac/Sinovac booster (p = 0.021). Additionally, a significantly higher rate of COVID-19 positivity was observed among patients who received the CoronaVac/Sinovac booster (p = 0.031). Heterologous COVID-19 booster vaccination is significantly more effective than homologous inactivated booster vaccination in enhancing immune responses and preventing new infections in RTRs. MFA and ACE inhibitor usage were independent factors affecting seropositivity. Additional COVID-19 vaccine doses are needed in this patient group.

Anti-HBs Seroprevalence in Blood Donors from Tyrol, Austria.

Background/Objectives: Antibodies against the hepatitis B surface antigen (anti-HBs) are a marker of immunity against hepatitis B virus (HBV) infections. There is uncertainty about the anti-HBs seroprevalence in the general population of Austria. Methods: We conducted a cross-sectional analysis in blood donors from the Federal State of Tyrol in Austria (August-September 2023) to estimate anti-HBs seroprevalence and median antibody levels. Results: We enrolled 3935 blood donors (median age 47.6 years [25th-75th percentile: 33.3-56.6]; 40.7% female), who were hepatitis B surface antigen negative and had no detectable HBV-DNA. Overall seroprevalence was 51.4% (95% CI: 49.8-52.9%). Anti-HBs seropositivity decreased with higher age (p < 0.001), with 70.3% (66.1-74.3%) being seropositive among participants < 25 years of age and 30.2% (24.2-36.9%) in those aged ≥ 65 years. More females than males were seropositive (54.3% [51.8-56.7%] vs. 49.4% [47.4-51.4%]; p = 0.003). Seroprevalence was significantly higher in urban than in rural areas in participants aged 40 to <55 (p = 0.045) and ≥55 years (p = 0.001). Among 2022 seropositive participants, the overall median anti-HBs antibody level was 539.3 IU/L (25th-75th percentile: 116.3-5417.0). Furthermore, 5% of the participants had an anti-HBs antibody level between 10 and <20 IU/L, 18% between 20 and <100 IU/L, and 77% ≥100 IU/L. Conclusions: Anti-HBs seroprevalence in blood donors from Tyrol, Austria, was 51.4% between August and September 2023 and differed across age, sex, and residence area. Catch-up vaccination programs, especially targeting the elderly living in rural areas, are needed to close HBV immunity gaps.

Plasmodium falciparum transmission based on merozoite surface protein 1 (msp1) and 2 (msp2) gene diversity and antibody responses in Ibadan, Nigeria

BackgroundNigeria is a major contributor to the global malaria burden. The genetic diversity of malaria parasite populations as well as antibody responses of individuals in affected areas against antigens of the parasite can reveal the transmission intensity, a key information required to control the disease. This work was carried out to determine the allelic frequency of highly polymorphic Plasmodium falciparum genes and antibody responses against schizont crude antigens in an area of Ibadan, Nigeria. Materials and methodsBlood was collected from 147 individuals with symptoms suspected to be malaria. Malaria infection was determined using a rapid diagnostic test (RDT), and msp1 and msp2 were genotyped by a nested PCR method. In addition, levels of IgG directed against P. falciparum FCR3S1.2 schizont extract was measured in ELISA. ResultsApproximately 25% (36/147) were positive for a P. falciparum infection in RDT, but only 32 of the positive samples were successfully genotyped. MAD20 was the most prevalent and K1 the least prevalent of the msp1 alleles. For msp2, FC27 was more prevalent than 3D7. The mean multiplicities of infection (MOI) were 1.9 and 1.7 for msp1 and msp2, respectively. IgG levels correlated positively with age, however there was no difference in median antibody levels between RDT-positive and RDT-negative individuals. ConclusionLow MOI has before been correlated with low/intermediate transmission intensity, however, in this study, similar levels of P. falciparum-specific antibodies between infected and non-infected individuals point more towards a high level of exposure and a need for further measures to control the spread of malaria in this area.

Preoperative Hepatitis B seroprevalence and AntiHbs Levels in Children Consulted for Dental Procedures Under Anaesthesia

Background/Aims: Hepatitis B virus infection continues to be a major global and national public health concern. The aim of this study was to examine the seroprevalence of hepatitis B virus in children who were consulted to child health and diseases before dental intervention and to share our findings with the healthcare personnel involved on this subject. Methods: A total of 932 children were enrolled in the study, of which 533 (57.2%) were boys and 399 (42.8%) were girls. In the blood samples taken; hepatitis B virus tests were studied with the Enzyme Linked Immuno Sorbent Assay method. The results of blood samples and demographic data of the patients were evaluated. Results: HBsAg positivity was not found in any of the patients (0%). AntiHbs seropositivity was found in 73.8% of the whole patient population. No statistically significant difference was detected when comparing the anti-HBs levels based on gender. The average age of children with antiHbs seropositive was found to be statistically significant lower than that of those with antiHBs negative. The median anti-HBS antibody levels were significantly higher in the group of children under 5 years old than in the other two age groups older than five years old in our study. When investigating the association between the level of antiHBs and age, a weak negative correlation was found. Conclusions: Our study showed that the antiHbs seropositivity is higher in Konya compared to previous studies. It suggests that the national vaccination program has a positive impact on antiHbs seroprevalence. Our study revealed that children under the age of five displayed the highest levels of anti-HBs seropositivity, while the anti-HBs levels diminished with advancing age.

High Concentration of Anti-SARS-CoV-2 Antibodies 2 Years after COVID-19 Vaccination Stems Not Only from Boosters but Also from Widespread, Often Unrecognized, Contact with the Virus.

This study follows 99 subjects vaccinated with Pfizer/BioNTech COVID-19 vaccines over two years, with particular focus on the last year of observation (between days 360 and 720). The response to the vaccination was assessed with Diasorin's SARS-CoV-2 TrimericSpike IgG. Screening for SARS-CoV-2 infection was performed with Abbott's SARS-CoV-2 Nucleocapsid IgG immunoassay. Data from questionnaires were also analyzed. Two years after the first vaccine dose administration, 100% of the subjects were positive for anti-spike SARS-CoV-2 IgG and the median antibody level was still high (3600 BAU/mL), dropping insignificantly over the last year. Simultaneously, a substantial increase in seropositivity in anti-nucleocapsid SARS-CoV-2 IgG was noted, reaching 33%. There was no statistically significant agreement between anti-N seropositivity and reported COVID-19. Higher anti-spike concentrations and lower COVID-19 incidence was seen in the older vaccinees. It was noted that only subjects boosted between days 360 and 720 showed an increase in anti-spike IgG concentrations. The higher antibody concentrations (median 7440 BAU/mL) on day 360 were noted in participants not infected over the following year. Vaccination, including booster administrations, and natural, even unrecognized, contact with SARS-CoV-2 entwined two years after the primary vaccination, leading to high anti-spike antibody concentrations.

Cell immunity to SARS-CoV-2 after natural infection and/or different vaccination regimens.

The aim of the study was to evaluate the humoral and cellular immunity after SARS-CoV-2 infection and/or vaccination according to the type of vaccine, number of doses and combination of vaccines. Volunteer subjects were sampled between September 2021 and July 2022 in Hospital Clínico San Carlos, Madrid (Spain). Participants had different immunological status against SARS-CoV-2: vaccinated and unvaccinated, with or without previous COVID-19 infection, including healthy and immunocompromised individuals. Determination of IgG against the spike protein S1 subunit receptor-binding domain (RBD) was performed by chemiluminescence microparticle immunoassay (CMIA) using the Architect i10000sr platform (Abbott). The SARS-CoV-2-specific T-cell responses were assessed by quantification of interferon gamma release using QuantiFERON SARS-CoV-2 assay (Qiagen). A total of 181 samples were collected, 170 were from vaccinated individuals and 11 from unvaccinated. Among the participants, 41 were aware of having previously been infected by SARS-CoV-2. Vaccinated people received one or two doses of the following vaccines against SARS-CoV-2: ChAdOx1-S (University of Oxford-AstraZeneca) (AZ) and/orBNT162b2 (Pfizer-BioNTech)(PZ). Subjects immunized with a third-booster dose received PZ or mRNA-1273 (Moderna-NIAID)(MD) vaccines. All vaccinees developed a positive humoral response (>7.1 BAU/ml), but the cellular response varied depending on the vaccination regimen. Only AZ/PZ combination and 3 doses of vaccination elicited a positive cellular response (median concentration of IFN- γ > 0.3 IU/ml). Regarding a two-dose vaccination regimen, AZ/PZ combination induced the highest humoral and cellular immunity. A booster with mRNA vaccine resulted in increases in median levels of IgG-Spike antibodies and IFN-γ as compared to those of two-dose of any vaccine. Humoral and cellular immunity levels were significantly higher in participants with previous infection compared to those without infection. Heterologous vaccination (AZ/PZ) elicited the strongest immunity among the two-dose vaccination regimens. The immunity offered by the third-booster dose of SARS-CoV-2 vaccine depends not only on the type of vaccine administered but also on previous doses and prior infection. Previous exposure to SARS-CoV-2 antigens by infection strongly affect immunity of vaccinated individuals.

Efficacy and safety of tixagevimab/cilgavimab as passive immunisation against COVID-19 infections in patients with hematological malignancies.

Monoclonal antibodies, as tixagevimab/cilgavimab, have been introduced as prophylaxis against COVID-19 infections in high-risk populations. However, data on efficacy are limited. This study investigates efficacy and tolerability of tixagevimab/cilgavimab in hematological patients under real-life conditions. Tixagevimab/cilgavimab was administered to 155 hematological patients (March-August 2022) at two Austrian centres. S/RBD-antibody assessments were performed before (T0), four weeks (T1), and six months (T2) after application. Side effects, the occurrence of COVID-19 infections, and the course of S/RBD-antibody titres were analysed retrospectively in relation to clinical variables. 155 hematological patients, who refused tixagevimab/cilgavimab, were included as a control group to compare the frequency of COVID-19 infections. Of all immunised patients (52.3% males; 91% triple vaccinated), 25.8% had a COVID-19 breakthrough infection (76% mild) compared to 43.9% in the control group. Patients with chronic lymphocytic leukaemia (CLL)/lymphoma were at highest risk of a COVID-19 infection (OR = 2.21; 95% CI 1.05-4.65; p = 0.037). After immunisation, a steep increase in median antibody levels (1193.4BAU/ml, IQR 0-2318.94) was observed in 67.8%, followed by a rapid decrease between T1 and T2 (465.95BAU/ml, IQR 0-1900.65.3) with the greatest declines in CLL/lymphoma (848.7BAU/ml, IQR 0-1949.6, p = 0.026). Side-effects occurred in 21.2% (CTCAE I/II). These real-world data indicate that S/RBD antibodies respond rapidly after passive immunisation in all hematological patients without safety concerns. Given the rapid decline in S/RBD antibodies, early booster immunisations should be considered for future scenarios in this vulnerable group.

Low antibody levels associated with significantly increased rate of SARS-CoV-2 infection in a highly vaccinated population from the US National Basketball Association.

SARS-CoV-2 antibody levels may serve as a correlate for immunity and could inform optimal booster timing. The relationship between antibody levels and protection from infection was evaluated in vaccinated individuals from the US National Basketball Association who had antibody levels measured at a single time point from September 12, 2021,to December 31, 2021. Cox proportional hazards models were used to estimate the risk of infection within 90 days of serologic testing by antibody level (<250, 250-800, and >800 AU/mL1 ), adjusting for age, time since last vaccine dose, and history of SARS-CoV-2 infection. Individuals were censored on date of booster receipt. The analytic cohort comprised 2323 individuals and was 78.2% male, 68.1% aged ≤40 years, and 56.4% vaccinated (primary series) with the Pfizer-BioNTech mRNA vaccine. Among the 2248 (96.8%) individuals not yet boosted at antibody testing, 77% completed their primary vaccine series 4-6 months before testing and the median (interquartile range) antibody level was 293.5 (interquartile range: 121.0-740.5) AU/mL. Those with levels <250 AU/mL (adj hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.5-3.7) and 250-800 AU/mL (adj HR: 1.5; 95% CI: 0.98-2.4) had greater infection risk compared to those with levels >800 AU/mL. Antibody levels could inform individual COVID-19 risk and booster scheduling.

A pilot study on the impact of parenteral vaccination of free-roaming dogs within the rabies control framework in Ukraine

This pioneering study is prompted by the imperative to enhance our understanding of a constituent within Ukraine's rabies control strategy, specifically focusing on the vaccination of free-roaming canines against rabies with a local vaccine in certain endemic rabies areas. The cross-sectional study encompassed the capture, sterilization, deworming, and rabies vaccination processes in 160 free-roaming dogs, followed by the collection of blood samples to examine RABV-specific neutralising antibodies in 16 dogs (10% of the vaccinated population), captured from sectors (territories) with a higher density of population and with higher density of previously vaccinated free-roaming dogs. Half of the targeted samples comprised males (n = 8), while the remaining half consisted of females (n = 8). The median of virus-neutralising antibody level was 0.58 IU/mL, with a minimum protective threshold of 0.5 IU/mL. Antibody titers below the 0.5 IU/mL threshold were detected in 25.0% (2/8) of the male group, and in 62.5% (5/8) of the female group. Notably, male dogs exhibited a higher median antibody level of 0.66 IU/mL, compared to females, who presented a median level of 0.26 IU/mL. However, no statistically significant difference was found between the male and female groups (P = 0.36). In general, more than half of the tested population (56.3%) exceeded the 0.5 IU/mL protective threshold 4 months post-vaccination. The inadequate levels of antibodies neutralizing the rabies virus are likely a result of a confluence of factors, including stressors such as nutritional and temperature-related challenges, along with variations in the responses of individual immune systems. Considering the endemic rabies situation and large population of free-roaming dogs in Ukraine, we suggest repeated vaccination for free-roaming dogs against rabies one year after the previous vaccination. In perspective, we suggest conducting large-scale epidemiological studies to assess the impact of animal-related, vaccine-related, and environment-related parameters on the efficacy of rabies vaccines used in Ukraine.

Anti-nucleocapsid antibody levels following initial and repeat SARS-CoV-2 infections in a cohort of long-term care facility residents in England (VIVALDI).

We have previously demonstrated that older residents of long-term care facilities (LTCF) in the UK show levels of anti-spike antibodies that are comparable to the general population following primary series and booster vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, data on the humoral response to other SARS-CoV-2 proteins associated with natural infection are scarce in this vulnerable population. We measured quantitative levels of anti-nucleocapsid antibodies in blood samples taken from LTCF residents and staff after initial and repeat SARS-CoV-2 infections, between December 2020 and March 2023. Data on SARS-CoV-2 infection and vaccination were obtained through linkage to national datasets. Linear mixed effects models were used to investigate anti-nucleocapsid antibody levels, using log10 scale, in relation to time from most recent infection. This included evaluation of associations between repeat infection, staff/resident status, age, sex, Omicron infection and vaccination history and peak antibody level and slope of decline with time. We analysed 405 antibody observations from 220 residents and 396 observations from 215 staff. Repeat infection was associated with 8.5-fold (95%CI 4.9-14.8-fold) higher initial (peak) median anti-nucleocapsid antibody level, with steeper subsequent slope of decline. There were no significant differences in antibody level associated with resident (vs. staff) status or age, but Omicron infection was associated with 3.6-fold (95%CI 2.4-5.4-fold) higher levels. There was stronger evidence of waning of antibody levels over time in a sensitivity analysis in which observations were censored in cases with suspected undetected repeat infection. We found similar levels of anti-nucleocapsid antibody in residents and staff of LTCFs. Repeat infection and infection with an Omicron strain were associated with higher peak values. There was evidence of waning of anti-nucleocapsid antibody levels over time.

Dynamics of humoral and cellular response to three doses of anti-SARS-CoV-2 BNT162b2 vaccine in patients with hematological malignancies and older subjects.

Few data are available about the durability of the response, the induction of neutralizing antibodies, and the cellular response upon the third dose of the anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in hemato-oncological patients. To investigate the antibody and cellular response to the BNT162b2 vaccine in patients with hematological malignancy. We measured SARS-CoV-2 anti-spike antibodies, anti-Omicron neutralizing antibodies, and T-cell responses 1 month after the third dose of vaccine in 93 fragile patients with hematological malignancy (FHM), 51 fragile not oncological subjects (FNO) aged 80-92, and 47 employees of the hospital (healthcare workers, (HW), aged 23-66 years. Blood samples were collected at day 0 (T0), 21 (T1), 35 (T2), 84 (T3), 168 (T4), 351 (T pre-3D), and 381 (T post-3D) after the first dose of vaccine. Serum IgG antibodies against S1/S2 antigens of SARS-CoV-2 spike protein were measured at every time point. Neutralizing antibodies were measured at T2, T3 (anti-Alpha), T4 (anti-Delta), and T post-3D (anti-Omicron). T cell response was assessed at T post-3D. An increase in anti-S1/S2 antigen antibodies compared to T0 was observed in the three groups at T post-3D. After the third vaccine dose, the median antibody level of FHM subjects was higher than after the second dose and above the putative protection threshold, although lower than in the other groups. The neutralizing activity of antibodies against the Omicron variant of the virus was tested at T2 and T post-3D. 42.3% of FHM, 80,0% of FNO, and 90,0% of HW had anti-Omicron neutralizing antibodies at T post-3D. To get more insight into the breadth of antibody responses, we analyzed neutralizing capacity against BA.4/BA.5, BF.7, BQ.1, XBB.1.5 since also for the Omicron variants, different mutations have been reported especially for the spike protein. The memory T-cell response was lower in FHM than in FNO and HW cohorts. Data on breakthrough infections and deaths suggested that the positivity threshold of the test is protective after the third dose of the vaccine in all cohorts. FHM have a relevant response to the BNT162b2 vaccine, with increasing antibody levels after the third dose coupled with, although low, a T-cell response. FHM need repeated vaccine doses to attain a protective immunological response.

2079. Maternal hybrid immunity to SARS-CoV-2 during pregnancy provides more durable infant antibody responses compared to natural infection alone

Abstract Background Immunity from natural infection and vaccination (hybrid) may provide more durable SARS-CoV-2 antibody responses; whether this increases durability of maternally-derived antibody responses in infants is unknown. Methods Participants with prior SARS-CoV-2 infection in pregnancy (anti-nucleocapsid [anti-N] IgG+ on enrollment or prior RT-PCR+ or antigen+) were enrolled between January 2021-August 2022. Blood samples collected in pregnancy, delivery/birth, 0-&amp;lt; 3 and 3-6 months postpartum were tested for anti-S+ IgG by Abbott Architect (positive: ≥50 AU/mL) and neutralizing antibodies (serum dilution inhibited infection by 50% [ND50 heat] ≥20 and R2 ≥0.9). Results Among 107 participants at enrollment in pregnancy, median age was 32 years (IQR 30-35) and median gestational age was 31 weeks (IQR 19.1–37.9). At delivery (median 19.7 weeks [IQR 14.3-30.0] from SARS CoV-2 diagnosis), unvaccinated participants and their infants were less likely to have anti-S IgG+ (maternal 87%; cord 86%) or neutralizing antibodies (maternal 86%; cord 75%) than vaccinated (≥1 dose) participants and their infants (maternal and cord both 100% anti-S IgG+ and neutralizing antibodies) (all p≤0.01). By 6 months of age, the proportion of infants of mothers who remained unvaccinated at birth with anti-S IgG+ and neutralizing antibody declined to 50% and 14% (anti-S IgG+ and neutralizing antibody, respectively) compared to 100% (anti-S IgG+ and neutralizing antibody) among infants with vaccinated mothers (all p&amp;lt; 0.01). Infants with anti-S IgG+ or neutralizing antibodies born to unvaccinated mothers had lower median antibody levels at birth (anti-S IgG log10 2.95 vs. 4.40 AU/ml; neutralization log10 1:2.37 vs. 1:4.00, all p&amp;lt; 0.01) and through 6 months of age (anti-S IgG log10 1.95 vs. 3.84 AU/ml, p&amp;lt; 0.01; log10 neutralization 1:1.34 vs. 1:3.20, p=0.11) vs. infants with mothers vaccinated prior to delivery. Neutralizing antibody responses among A) pregnant people with prior SARS-CoV-2 infection during pregnancy and B) their infants by maternal vaccination status *† *Among participants and their infants with positive neutralizing antibodies (ND50 heat ≥20 and R2 ≥0.9). †Maternal vaccination status is at time of blood sample collection; for infants refers to maternal vaccination status at time of delivery. Conclusion SARS-CoV-2 infection alone during pregnancy did not provide persistent antibody responses in infants through 6 months of age. Maternal vaccination provided more durable antibody responses in participants with prior SARS-CoV-2, potentially providing protection to vulnerable infants in the months prior to their own COVID-19 vaccine eligibility. Disclosures Sylvia M. LaCourse, MD, MPH, Merck: Grant/Research Support Alex L. Greninger, MD, PhD, MS, MPhil, Abbott Diagnostics: central testing|Cepheid: central testing|Hologic Inc: central testing|Janssen Infectious Disease: central testing|Novavax, Inc.: central testing|Pfizer, Inc.: central testing Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant Alison L. Drake, PhD, MPH, Merck: Grant/Research Support

2344. Clinical Profile and Immunologic Response from COVID-19 Vaccine Among People Living with HIV Enrolled in a Treatment Hub in the Philippines

Abstract Background SARS-CoV-2 has caused more than 1 million deaths worldwide. Several studies showed that People with HIV had higher rates of hospitalization and mortality with COVID-19 compared with people without HIV but data on serologic response to COVID-19 vaccine among People Living with HIV (PLHIV) is still limited. Methods A prospective cohort study on determination of serologic response to COVID-19 vaccine among completely vaccinated PLHIV enrolled in a treatment hub in the Philippines until December 31, 2021 was done. Baseline demographics were collected via chart review. History of COVID-19 infection was also asked during enrollment, on follow-up and at the end of 6 months after the 2nd dose of vaccination. Blood Extraction were done on enrollment and on follow-up visit to the treatment hub. All the specimen were processed using the SARS-CoV2 ( RocheElecsys Anti-SARS-CoV2 spike (S) protein assays. Results A total of 261 PLHIV who received vaccination from February 11, 2021 to December 29, 2021 were enrolled in the study. The participants received any of the following vaccine brands: CoronoVac/Sinovac (41%), Oxford-AstraZeneca (20.7%), Pfizer-BioNTech (21.5%), Moderna (14.2% and Janseen (2.7%). Univariate analysis showed that presence of opportunistic infection, HIV Viral load , Antiretroviral(ARV) Status, COVID-19 Vaccine brand were all significant predictors of antibody response. On multiple regression analysis, only the Vaccine Brand and Viral load remained significant. Sinovac gave a lower median antibody level and seroconversion rate as compared to other vaccine brands. HIV Viral load &amp;gt; 1000 copies/ml was predictive of lower antibody response. Conclusion In this study among PLHIV, the type of vaccine and HIV viral load were significant predictors of antibody response to COVID-19 Vaccine. Specifically, Sinovac COVID-19 Vaccine gave a lower Median SARS-CoV-2 IgG(S) Antibody and Seroconversion rate as compared to other Vaccine brands. HIV Viral load &amp;gt; 1000 copies/ml was predictive of lower antibody response to COVID-19 Vaccine . Overall, the antibody response peaked at 2-4 weeks after vaccination and decreases thereafter. Disclosures All Authors: No reported disclosures

A 12-month follow-up of the immune response to SARS-CoV-2 primary vaccination: evidence from a real-world study.

A real-world population-based longitudinal study, aimed at determining the magnitude and duration of immunity induced by different types of vaccines against COVID-19, started in 2021 by enrolling a cohort of 2,497 individuals at time of their first vaccination. The study cohort included both healthy adults aged ≤65 years and elderly subjects aged >65 years with two or more co-morbidities. Here, patterns of anti-SARS-CoV-2 humoral and cell-mediated specific immune response, assessed on 1,182 remaining subjects, at 6 (T6) and 12 months (T12) after the first vaccine dose, are described. At T12 median anti-Spike IgG antibody levels were increased compared to T6. The determinants of increased anti-Spike IgG were the receipt of a third vaccine dose between T6 and T12 and being positive for anti-Nucleocapside IgG at T12, a marker of recent infection, while age had no significant effect. The capacity of T12 sera to neutralize in vitro the ancestral B strain and the Omicron BA.5 variant was assessed in a subgroup of vaccinated subjects. A correlation between anti-S IgG levels and sera neutralizing capacity was identified and higher neutralizing capacity was evident in healthy adults compared to frail elderly subjects and in those who were positive for anti-Nucleocapside IgG at T12. Remarkably, one third of T12 sera from anti-Nucleocapside IgG negative older individuals were unable to neutralize the BA.5 variant strain. Finally, the evaluation of T-cell mediated immunity showed that most analysed subjects, independently from age and comorbidity, displayed Spike-specific responses with a high degree of polyfunctionality, especially in the CD8 compartment. In conclusion, vaccinated subjects had high levels of circulating antibodies against SARS-CoV-2 Spike protein 12 months after the primary vaccination, which increased as compared to T6. The enhancing effect could be attributable to the administration of a third vaccine dose but also to the occurrence of breakthrough infection. Older individuals, especially those who were anti-Nucleocapside IgG negative, displayed an impaired capacity to neutralize the BA.5 variant strain. Spike specific T-cell responses, able to sustain immunity and maintain the ability to fight the infection, were present in most of older and younger subjects assayed at T12.

Prospective Assessment of Humoral and Cellular Immune Responses to a Third COVID-19 mRNA Vaccine Dose Among Immunocompromised Individuals.

Improved coronavirus disease 2019 (COVID-19) prevention is needed for immunocompromised individuals. A prospective study was performed of health care workers (HCW) and immunocompromised participants with baseline serology following 2 mRNA vaccine doses and who were retested after dose 3 (D3); multivariable regression was used to identify predictors of serological responses. IFN-γ/TNF-α T-cell responses were assessed in a subset. In total, 536 participants were included: 492 immunocompromised (206 solid organ transplant [SOT], 128 autoimmune, 80 hematologic malignancy [HM], 48 solid tumor, 25 HIV), and 44 HCW. D3 significantly increased spike IgG levels among all, but SOT and HM participants had the lowest median antibody levels post-D3 (increase from 0.09 to 0.83 and 0.27 to 1.92, respectively), versus HCW and persons with HIV, autoimmune conditions, and solid tumors (increases from 4.44 to 19.79, 2.9 to 15.75, 3.82 to 16.32, and 4.1 to 25.54, respectively). Seropositivity post-D3 was lowest for SOT (49.0%) and HM (57.8%), versus others (>90%). Neutralization post-D3 was lowest among SOT and HM. Predictors of lower antibody levels included low baseline levels and shorter intervals between vaccines. T-cell responses against spike increased significantly among HCW and nonsignificantly among immunocompromised individuals. D3 significantly improves serological but not T-cell responses among immunocompromised individuals. SOT and HM patients have suboptimal responses to D3.

Factors Affecting SARS-CoV-2 IgG Production after Vaccination and/or Disease: A Large-Scale Seroprevalence Study.

This study aimed at identifying factors influencing SARS-CoV-2-specific IgG antibody levels after vaccination and/or infection. Between January 2022 and March 2023, 2000 adults (≥18 years, Salzburg, Austria) participated in this population-based seroprevalence study by providing 3 mL of blood to detect SARS-CoV-2-specific IgG antibodies using an anti-SARS-CoV-2 IgG quantitative assay and by completing a self-designed questionnaire including anthropometric factors, vaccination information, and medical history. For 77 of the participants, a time-course study up to 24 weeks post vaccination or quarantine end was performed. Convalescent-only subjects had the lowest median antibody titer (65.6 BAU/mL) compared to vaccinated and hybrid immunized subjects (p-value < 0.0001) The type of vaccine as well as vaccine combinations significantly influenced the levels of SARS-CoV-2 spike-protein-specific IgG, ranging from a median antibody level of 770.5 BAU/mL in subjects who were vaccinated only to 3020.0 BAU/mL in hybrid immunized subjects (p-value < 0.0001). Over time, a significant decline in the levels of neutralizing antibodies was found. Depending on the subpopulation analyzed, further significant influencing factors included sex assigned at birth, disease severity, chronic diseases, and medication. A hybrid immunization resulted in more robust immune responses. Nevertheless, there were multiple other factors impacting these responses. This knowledge should be included in future vaccination strategies and serve as a guide in the development of personalized medicine.

Thyroid peroxidase antibody titers, thyroid function, and iodine nutrition status of pregnant normotensive and preeclamptic women in Eastern Cape South Africa

Autoimmune thyroid disease, one of the main risk factors for hypothyroidism, is associated with adverse pregnancy outcomes. The burden of autoimmune thyroid disease in pregnancy and its association with thyroid function among normotensive pregnant women and pregnant women with hypertension in South Africa are not known. This study aimed to establish the magnitude of thyroid peroxidase autoantibodies in pregnancy in the Eastern Cape of South Africa and its relationship with iodine nutrition status and preeclampsia. Overall, 60 randomly selected normotensive pregnant controls at term and 120 pregnant participants with preeclampsia in the third trimester of pregnancy going to the Mthatha Regional Hospital and the Nelson Mandela Academic Hospital in the Eastern Cape Province who had complete data on thyroid peroxidase antibody titers, urinary iodine concentrations, serum thyroid-stimulating hormones, and free triiodothyronine, free thyroxine, and thyroglobulin levels were enrolled in this unmatched case-control study. The cases and controls had similar mean chronological age (23.8 vs 24.0 years), body mass index (29.4 vs 28.8 kg/m2), and median parity (both 1) (P>.05). The controls had a higher mean gestational age than participants with preeclampsia (38.5 vs 33.7 weeks, respectively; P<.001). Both participants with preeclampsia and normotensive participants had median thyroid peroxidase antibody levels consistent with a negative thyroid autoimmune status. Participants with preeclampsia had higher but nonstatistically significant median thyroid peroxidase antibody (2.14 vs 1.77 IU/L), thyroglobulin (25.9 vs 21.3 µg/L), and thyroid-stimulating hormone (2.4 vs 2.3 mIU/L) levels (P>.05) and significantly lower median urinary iodine concentration (123.4 vs 188.6 µg/L), free thyroxine (13.2 vs 14.1 pmol/L), and free triiodothyronine (4.3 vs 4.6 pmol/L) levels (P<.05) than normotensive controls. Thyroid peroxidase antibodies were positively correlated with thyroglobulin, urinary iodine concentration, and thyroid-stimulating hormone. In the rural Eastern Cape of South Africa, pregnant women in the third trimester of pregnancy have thyroid peroxidase antibody titers that show negative thyroid autoimmune status. Insufficient iodine intake, other than thyroid autoimmune disease, seems to be the underlying cause of the lower free triiodothyronine and free thyroxine levels observed among women with preeclampsia.

Humoral Response After Two Doses of COVISHIELDTM Vaccine in Patients Undergoing Maintenance Hemodialysis.

Maintenance hemodialysis (MHD) patients are at increased risk of contracting coronavirus disease 2019 (COVID-19). Vaccine against COVID-19 offers the benefit of protection from severe illness. In this study, we assessed the humoral response after two doses of the COVISHIELDTM vaccine in MHD patients. In a prospective cohort study, the humoral response with two doses of the COVISHIELDTM vaccine was assessed after 14 ± 2 days of the second dose. The COVIPROTECT antibody titers against the spike protein were measured using the electrochemiluminescence immunoassay (ELECSYS, Roche Diagnostics International Ltd.). Data were analyzed to determine the predictors of antibody response. Between February and October 2021, 50 MHD patients were assessed. The mean age was 55.8 ± 10.8 years, and 72% were males. A total of 48 (96%) MHD patients have seropositivity. The median level of spike protein antibody was 579 U/mL [interquartile range (IQR25-75) 166-1852.75]. Compared to patients with no COVID-19 infection history, the median levels of antibodies were significantly higher in those with a history of COVID-19 (1047 vs 297 U/mL, p = 0.011). The antibody titers did not differ by age (p = 0.269), presence of comorbidities such as hypertension (p = 0.341), diabetes mellitus (p = 0.719) or ischemic heart disease (IHD) (p = 0.695), dialysis vintage (p = 0.660), and timing of diagnosis of COVID-19 in relation to vaccination (p = 0.261). Adverse events (AEs) occurred in one-third of patients that were mild and self-limiting. No serious AEs were observed in any patient. In MHD patients, two doses of the COVISHIELDTM vaccine induced a substantial humoral response. Prior history of COVID-19 resulted in a higher antibody response. Thus, the COVISHIELDTM vaccine is efficacious and safe for use in patients with MHD. How to cite this article: Balwani MR, Pasari AS, Bawankule C, et al. Humoral Response After Two Doses of COVISHIELDTM Vaccine in Patients Undergoing Maintenance Hemodialysis. J Assoc Physicians India 2023;71(9):56-60.

High Levels of Anti-SARS-CoV-2 Receptor-Binding Domain (RBD) Antibodies One Year Post Booster Vaccinations among Hospital Workers in Indonesia: Was the Second Booster Needed?

In August 2022, Indonesia prioritized healthcare workers to receive the second booster dose. We conducted a sequential serosurvey to understand the dynamics of the antibody titers. The first serosurvey, which was conducted in June 2021, 1-6 months after Sinovac vaccination, showed a median antibody level of 41.4 BAU/mL (interquartile range (IQR): 10-629.4 BAU/mL). The second serosurvey was conducted one month (August 2021) after the first Moderna booster vaccine and showed a median level of 4000 BAU/mL (IQR: 3081-4000 BAU/mL). The last serosurvey was conducted a year (August 2022) after the booster and showed a median level of 4000 BAU/mL (IQR: 4000-4000 BAU/mL). In this last survey, only 39 (11.9%) of healthcare workers had antibody levels below the maximum level of 4000 BAU/mL. Thus, one year after the first booster dose, we did not observe the waning of antibody levels. The average increase was perhaps because of natural infection. Based on these considerations, we believe that a second booster dose was not necessary for this category of subjects at that time. Because vaccine supply is often limited, priority could be given to the general population or other high-risk patient groups with low antibody titers based on serological tests.

Safety and Immunogenicity of Radiation-Attenuated PfSPZ Vaccine in Equatoguinean Infants, Children, and Adults.

The radiation-attenuated Plasmodium falciparum sporozoites (PfSPZ) Vaccine has demonstrated safety and immunogenicity in 5-month-old to 50-year-old Africans in multiple trials. Except for one, each trial has restricted enrollment to either infants and children or adults < 50 years old. This trial was conducted in Equatorial Guinea and assessed the safety, tolerability, and immunogenicity of three direct venous inoculations of 1.8 × 106 or 2.7 × 106 PfSPZ, of PfSPZ Vaccine, or normal saline administered at 8-week intervals in a randomized, double-blind, placebo-controlled trial stratified by age (6-11 months and 1-5, 6-10, 11-17, 18-35, and 36-61 years). All doses were successfully administered. In all, 192/207 injections (93%) in those aged 6-61 years were rated as causing no or mild pain. There were no significant differences in solicited adverse events (AEs) between vaccinees and controls in any age group (P ≥ 0.17). There were no significant differences between vaccinees and controls with respect to the rates or severity of unsolicited AEs or laboratory abnormalities. Development of antibodies to P. falciparum circumsporozoite protein occurred in 67/69 vaccinees (97%) and 0/15 controls. Median antibody levels were highest in infants and 1-5-year-olds and declined progressively with age. Antibody responses in children were greater than in adults protected against controlled human malaria infection. Robust immunogenicity, combined with a benign AE profile, indicates children are an ideal target for immunization with PfSPZ Vaccine.