IgG Titers Research Articles

Clinical characteristics, anti-SARS-CoV-2 IgG titers, and inflammatory markers in individuals with post-COVID-19 condition in Kenya: a cross-sectional study.

Post-coronavirus disease 2019 (post-COVID-19) is associated with considerable morbidity and reduced quality of life. However, studies characterizing the post-COVID-19 condition in Kenya are limited. This study aimed to determine the prevalence of post-COVID-19 condition and determine the clinical characteristics, anti-SARS-CoV-2 IgG titers, and concentrations of inflammatory markers of individuals with post-COVID-19 condition in Kenya. This descriptive cross-sectional study was conducted at the Kenyatta University Health Unit, Kenya. Demographic and clinical data were collected using a questionnaire. The serum levels of anti-SARS-CoV-2 antibodies, interleukin 6 (IL-6), and C-reactive protein (CRP) were quantified by enzyme-linked immunosorbent assays. Independent samples t-test was used to compare the anti-SARS-CoV-2 IgG, IL-6, and CRP levels between the participants with and without post-COVID-19 symptoms. The case definition for post-COVID-19 condition was persistence of acute COVID-19 symptoms or emergence of new symptoms 3 months after COVID-19 diagnosis, symptoms lasting for ≥2 months, and absence of any other etiological basis to explain the symptoms. A total of 189 volunteers were recruited in this study (median age: 21 years, range: 18-71 years; male, 49.2%). Forty participants reported having had at least one COVID-19 positive diagnosis in the past, of which 12 (30%) complained of post-COVID-19 symptoms. Significant differences in the number and duration of symptoms were observed between the individuals with and without post-COVID-19 symptoms (t-statistic = 2.87, p = 0.01; t-statistic = 2.39, p = 0.02, respectively). However, no significant differences in serum levels of anti-SARS-CoV-2 IgG, IL-6, and CRP were observed between the two groups (P = 0.08, 0.9, and 0.28, respectively). These findings suggest that post-COVID-19 condition is a health concern even for a relatively young population in Kenya and globally. This condition requires more attention and well-designed studies to better define it and identify clinical chemistry markers that can be used for its diagnosis.

Ala-Cys-Cys-Ala dipeptide dimer alleviates problematic cysteine and cystine levels in media formulations and enhances CHO cell growth and metabolism

Cysteine and cystine are essential amino acids present in mammalian cell cultures. While contributing to biomass synthesis, recombinant protein production, and antioxidant defense mechanisms, cysteine poses a major challenge in media formulations owing to its poor stability and oxidation to cystine, a cysteine dimer. Due to its poor solubility, cystine can cause precipitation of feed media, formation of undesired products, and consequently, reduce cysteine bioavailability. In this study, a highly soluble cysteine containing dipeptide dimer, Ala-Cys-Cys-Ala (ACCA), was evaluated as a suitable alternative to cysteine and cystine in CHO cell cultures. Replacing cysteine and cystine in basal medium with ACCA did not sustain cell growth. However, addition of ACCA at 4 mM and 8 mM to basal medium containing cysteine and cystine boosted cell growth up to 15% and 27% in CHO-GS and CHO–K1 batch cell cultures respectively and led to a proportionate increase in IgG titer. 13C-Metabolic flux analysis revealed that supplementation of ACCA reduced glycolytic fluxes by 20% leading to more efficient glucose metabolism in CHO–K1 cells. In fed-batch cultures, ACCA was able to replace cysteine and cystine in feed medium. Furthermore, supplementation of ACCA at high concentrations in basal medium eliminated the need for any cysteine equivalents in feed medium and increased cell densities and viabilities in fed-batch cultures without any significant impact on IgG charge variants. Taken together, this study demonstrates the potential of ACCA to improve CHO cell growth, productivity, and metabolism while also facilitating the formulation of cysteine- and cystine-free feed media. Such alternatives to cysteine and cystine will pave the way for enhanced biomanufacturing by increasing cell densities in culture and extending the storage of highly concentrated feed media as part of achieving intensified bioproduction processes.

Longevity of immune response after a single dose of typhoid conjugate vaccine against Salmonella Typhi among children in Hyderabad, Pakistan

ObjectivesTyphoid remains a persistent contributor to childhood morbidity in communities lacking sanitation infrastructure. Typhoid conjugate vaccine (TCV) is effective in reducing disease risk in vaccinees; however, the duration of protection is unknown. This study measured the longevity of immune response to TCV in children aged under 10 years in Hyderabad, Pakistan, where an outbreak of extensively drug-resistant typhoid has been ongoing. MethodsA subset of children who received the TCV as part of the outbreak response were enrolled purposively from March 2018 to February 2019. The participants were followed up until January 2023. Blood samples were taken at baseline, 4-6 weeks, 6 months, and annually 1-4 years after vaccination to measure anti-Vi immunoglobulin (Ig) G levels using enzyme-linked immunosorbent assay. Active phone-based surveillance was performed to identify breakthrough infections. Blood culture was offered to any child with a history of fever ≥3 days within the last 7 days. A total of 81 children received a second dose of TCV in November 2019 during a catch-up campaign organized by the Sindh government. ResultsNearly all participants seroconverted (802 of 837; 95.8%) at 4-6 weeks after vaccination. A total of 4 years after vaccination, 438 of 579 (75.6%) participants remained above the seroconversion threshold. The geometric mean titer (U/mL) of anti-Vi IgG at 4-6 weeks was 832.6 (95% confidence interval [CI]: 768.0-902.6); at 4 years after vaccination, the geometric mean titers in children aged 6 months to 2 years (12.6, [95% CI: 9.8-16.3]) and >2-5 years (40.1, [95% CI: 34.4-46.6]) were lower than in children aged >5-10 years (71.1, [95% CI: 59.5-85.0]). During 4 years of follow-up, nine children had culture-confirmed Salmonella Typhi infection; these infections occurred after a median duration of 3.4 years. All enteric fever cases seroconverted at 4-6 weeks after vaccination and seven (70.0%) remained seroconverted 4 years after vaccination. ConclusionsWe observed 95.8% seroconversion after a single dose of TCV. There was a decay in anti-Vi IgG titers, and, at 4 years, approximately 75.6% remained seroconverted. There was a faster decay in children aged ≤2 years. Breakthrough infections were documented after a median 3.4 years after vaccination.

Factors Influencing Breast Milk Antibody Titers during the Coronavirus Disease 2019 Pandemic: An Observational Study.

The COVID-19 pandemic has highlighted the role of breastfeeding in providing passive immunity to infants via specific anti-SARS-CoV-2 antibodies in breast milk. We aimed to quantify these antibodies across different lactation stages and identify influencing factors. This prospective study involved mother-child dyads from Innsbruck University Hospital, Austria, with a positive maternal SARS-CoV-2 test during pregnancy or peripartum between 2020 and 2023. We collected breast milk samples at various lactation stages and analyzed anti-Spike S1 receptor-binding domain (S1RBD) immunoglobulins (Ig). Maternal and neonatal data were obtained from interviews and medical records. This study included 140 mothers and 144 neonates. Anti-S1RBD-IgA (72.0%), -IgG (86.0%), and -IgM (41.7%) were highly present in colostrum and decreased as milk matured. Mothers with natural infection and vaccination exhibited higher anti-S1RBD-IgA and -IgG titers in all milk stages. Mothers with moderate to severe infections had higher concentrations of anti-S1RBD-IgA and -IgG in transitional milk and higher anti-S1RBD-IgA and -IgM in mature milk compared to those with mild or asymptomatic infections. Variations in antibody responses were also observed with preterm birth and across different virus waves. This study demonstrates the dynamic nature of breast milk Ig and underscores the importance of breastfeeding during a pandemic.

Augmented humoral response to third and fourth dose of SARS-CoV-2 mRNA vaccines in lung transplant recipients

BackgroundSince lung transplant recipients (LTRs) exhibit low immunogenicity after two doses of SARS-CoV-2 mRNA vaccines, optimal vaccine strategies for SARS-CoV-2 are required in LTRs. This study aimed to investigate the efficacy and safety of the third and fourth doses of the SARS-CoV-2 mRNA vaccines in LTRs. MethodsWe conducted a single-center study of 73 LTRs and 23 healthy controls (HCs). Participants received two-to-four doses of SARS-CoV-2 mRNA vaccines. The LTRs were divided into three groups based on the number of vaccine dose. IgG titers against SARS-CoV-2 spike protein were measured, and adverse events were assessed. Factors associated with humoral response were analyzed using univariate and multivariate analyses. ResultsThe Dose 4 group (n = 27) had a higher humoral response rate (P = 0.018) and higher levels of anti-SARS-CoV-2 IgG antibody (P = 0.04) than the Dose 2 group (n = 14). The Dose 3 group (n = 32) had lower humoral response rates (P = 0.005) and levels of anti-SARS-CoV-2 IgG antibody (P = 0.0005) than the HCs (n = 23) even after the same dose. Systemic adverse events were milder in the LTRs than in the HCs (P < 0.05). Increased number of vaccine dose was identified as a predictor of positive humoral response (P = 0.021). ConclusionBooster doses of SARS-CoV-2 mRNA vaccines may enhance humoral response with mild adverse events in LTRs. Repeated vaccination might be warranted for LTRs to prevent SARS-CoV-2 infection.

Antibody levels against respiratory syncytial virus fusion protein conformations and lack of association with life-threatening infection in previously healthy infants

BackgroundHumoral immune response against the pre-fusion (pre-F) conformation of respiratory syncytial virus (RSV) F protein has been proposed to play a protective role against infection. An RSV pre-F maternal vaccine has been recently approved in several countries to protect young infants against RSV. We aimed to assess serum IgG titers against the pre-F and post-F conformations of RSV F protein and their association with life-threatening RSV disease (LTD) in previously healthy infants. MethodsA prospective cohort study including hospitalized infants <12 months with a first RSV infection was conducted during 2017–2019. Patients with LTD required intensive care and mechanical respiratory assistance. RSV pre-F exclusive and post-F antibody responses were determined by post-F competition and non-competition immunoassays, respectively, and neutralizing activity was measured by plaque reduction neutralization test. ResultsFifty-eight patients were included; the median age was 3.5 months and 41 % were females. Fifteen patients developed LTD. RSV F-specific antibody titers positively correlated with neutralizing antibody titers in acute and convalescent phases but, importantly, they did not associate with LTD. Acute RSV pre-F exclusive and post-F IgG titers negatively correlated with patient age (P = 0.0007 and P < 0.0001), while a positive correlation was observed between the fold changes in RSV F-specific antibody titers between convalescent and acute phase and patient age (P = 0.0014 and P < 0.0001). Infants ≤2 months exhibited significantly lower fold-changes in RSV F-specific and neutralizing antibody titers between convalescence and acute phase than older infants. Additionally, acute RSV antibody titers showed no correlation with nasal RSV load and, furthermore, nasal viral load was not associated with the development of LTD. ConclusionsThis study highlights that protection against life-threatening RSV disease is not necessarily antibody-dependent. Further characterization of the immune response against RSV and its role in protection against severe disease is important for the development of the safest possible preventive strategies.

Lymphocytic Choriomeningitis Virus Infections in Hungary between 2017-2023-Investigation of the First Congenital Infections.

Lymphocytic choriomeningitis virus (LCMV) is a neglected rodent-borne arenavirus, primarily spread by common house mouse species. Acquired human infections range from asymptomatic to mild flu-like symptoms and self-resolving neurological diseases. In contrast, intrauterine LCMV infection is associated with high mortality and morbidity. Infection of the fetus often leads to fetal death, and surviving fetuses may develop vision impairment and central nervous system developmental disorders. LCMV is mainly diagnosed by serological methods using in-house indirect immunofluorescence assays. LCMV nucleic acid is detected by the nested RT-PCR method and confirmed by Sanger sequencing. In Hungary, 23 acquired lymphocytic choriomeningitis cases were diagnosed between 2017 and 2023. Ten out of 23 confirmed patients proved to be positive by the PCR method. Two cases of intrauterine LCMV infections were detected in 2019 and 2021, respectively. The IgG antibody titers measured in the infant's serum samples were much higher than the IgG titers of the maternal serum samples. Both IgM and IgA antibodies were detectable in the infants' sera. As the microbiological diagnosis of LCMV is rather challenging and the symptoms are very similar to the clinical picture of other common teratogenic pathogens such as cytomegalovirus or Toxoplasma gondii, intrauterine LCMV infections might still be underdiagnosed.

Modulation of T-Cell-Dependent Humoral Immune Response to Influenza Vaccine by Multiple Antioxidant/Immunomodulatory Micronutrient Supplementation.

Notwithstanding prevalence gaps in micronutrients supporting immune functions, the significance of their deficits/supplementation for the efficacy of vaccines is underinvestigated. Thus, the influence of supplementation combining vitamins C and D, zinc, selenium, manganese, and N-acetyl cysteine on immune correlates/surrogates of protection conferred by a quadrivalent influenza vaccine (QIV) in mice was investigated. The supplementation starting 5 days before the first of two QIV injections given 28 days apart increased the serum titres of total and neutralizing IgG against each of four influenza strains from QIV. Accordingly, the frequencies of germinal center B cells, follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells increased in secondary lymphoid organs (SLOs). Additionally, the supplementation improved already increased IgG response to the second QIV injection by augmenting not only neutralizing antibody production, but also IgG2a response, which is important for virus clearance, through favoring Th1 differentiation as indicated by Th1 (IFN-γ)/Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely partly reflected antioxidant action of the supplement as indicated by splenic redox status analyses. Thus, the study provides a solid scientific background for further research aimed at repurposing the use of this safe and inexpensive micronutrient combination to improve response to the influenza vaccine.

Pure red cell aplasia among ABO mismatched hematopoietic stem cell transplant recipients: a 13-years retrospective study and literature review.

Pure red cell aplasia (PRCA) is a possible complication after allogeneic hematopoietic stem cell transplantation (HSCT) with major ABO incompatibility. Patients experience delayed engraftment of the erythroid series, with prolonged transfusion-dependent anemia and iron overload. We performed a revision of the most recent literature about post-HSCT PRCA treatment procedures. Moreover, we conducted a retrospective study, over the last 13-years, which included all consecutive major ABO mismatched HSCT performed in our unit, with the aim to assess PRCA incidence, risk factors, and response to different treatments. Overall, 194 patients received a major ABO mismatched transplant from 2010 to 2022. For each patient, data about demographic and transplant characteristics, engraftment, blood transfusion, and possible treatment received were collected. The literature review returned 23 eligible papers on PRCA treatment, with high success rate using plasma-exchange (PEX) and immunoadsorption procedures, daratumumab, and eltrombopag. Our study identified a total of 24 cases of PRCA. Among risk factors for PRCA development, we have found older recipient age (p=0.01), high pre-HSCT IgG and IgM IHA titer (p<0.0001), major rather than bidirectional ABO incompatibility (p=0.02), low T CD8 lymphocyte count in the graft (p=0.006), relative donor (p=0.02) and bone marrow as stem cell source (p=0.002). However, multivariate analysis confirmed only pre-HSCT IgG IHA titer as the unique risk factor for PRCA occurrence. The optimal cut-off value of pre-HSCT IgG IHA for PRCA development, resulted to be 1/64, with a 100% sensitivity and 68.8% specificity (p<0.0001). All patients with PRCA had received rhEPO and transfusion support and 20 patients received additional treatments like PEX, rituximab, and more recently daratumumab. Comprehensively, PEX and rituximab obtained a response in half of the cases, at a variable time, while the few cases of patients we treated with daratumumab suggest promising results. The overall response rate in our cohort was 75%, with significantly better survival (94.4% vs. 16.7%) and lower transplant-related mortality (6.3% vs. 80%) for PRCA responders. Standardized guidelines on when and how to treat PRCA are necessary because the current treatment is controversial among centers.

Severe bilateral retinal vasculitis as a delayed manifestation of rickettsial infection

Ophthalmic manifestations of rickettsial infections are reported as mostly asymptomatic and self-limiting. A 27-year-old woman, 29 weeks pregnant, recently treated for rickettsial infection, presented ten days following discharge with visual blurring and was diagnosed to have severe bilateral retinal vasculitis. Rickettsial antibody testing (indirect immunofluorescence assay) revealed Rickettsia conorii IgG titer &gt;1:128. Antinuclear antibody, retroviral, syphilis and toxoplasmosis screens were negative. Bilateral intra-vitreous triamcinolone, azithromycin and prednisolone were administered. However, despite some improvement, a residual visual deficit remained. This case report highlights the possibility of debilitating visual loss following rickettsial infections, need for ophthalmic screening at diagnosis and prompt treatment initiation.

Specific long-term changes in anti-SARS-CoV-2 IgG modifications and antibody functions in mRNA, adenovector, and protein subunit vaccines.

Various vaccine platforms were developed and deployed against the COVID-19 disease. The Fc-mediated functions of IgG antibodies are essential in the adaptive immune response elicited by vaccines. However, the long-term changes of protein subunit vaccines and their combinations with messenger RNA (mRNA) vaccines are unknown. A total of 272 serum and plasma samples were collected from individuals who received first to third doses of the protein subunit Medigen, the mRNA (BNT, Moderna), or the adenovector AstraZeneca vaccines. The IgG subclass level was measured using enzyme-linked immunosorbent assay, and Fc-N glycosylation was measured using liquid chromatography coupled to tandem mass spectrometry. Antibody-dependent-cellular-phagocytosis (ADCP) and complement deposition (ADCD) of anti-spike (S) IgG antibodies were measured by flow cytometry. IgG1 and 3 reached the highest anti-S IgG subclass level. IgG1, 2, and 4 subclass levels significantly increased in mRNA- and Medigen-vaccinated individuals. Fc-glycosylation was stable, except in female BNT vaccinees, who showed increased bisection and decreased galactosylation. Female BNT vaccinees had a higher anti-S IgG titer than that of males. ADCP declined in all groups. ADCD was significantly lower in AstraZeneca-vaccinated individuals. Each vaccine produced specific long-term changes in Fc structure and function. This finding is critical when selecting a vaccine platform or combination to achieve the desired immune response.

Intranasal Vaccination with Recombinant TLR2-Active Outer Membrane Vesicles Containing Sequential M2e Epitopes Protects against Lethal Influenza a Challenge.

Influenza is a highly contagious respiratory disease, resulting in an estimated 3 to 5 million cases of severe illness annually. While most influenza vaccines are administered parenterally via injection, one shortcoming is that they do not generate a strong immune response at the site of infection, which can become important in a pandemic. Intranasal vaccines can generate both local and systemic protective immune responses, can reduce costs, and enhance ease of administration. Previous studies showed that parenterally administered outer membrane vesicles (OMVs) that carry sequences of the M2e protein (OMV-M2e) protect against influenza A/PR8 challenge in mice and ferrets. In the current study, we measured the effectiveness of the intranasal route of the OMV-M2e vaccine against the influenza A/PR8 strain in mice. We observed high anti-M2e IgG and IgA titers post-challenge in mice vaccinated intranasally with OMV-M2e. In addition, we observed a Th1/Tc1 bias in the vaccinated mice, and an increased Th17/Tc17 response, both of which correlated with survival to A/PR8 challenge and significantly lower lung viral titers. We conclude that the intranasal-route administration of the OMV-M2e vaccine is a promising approach toward generating protection against influenza A as it leads to an increased proinflammatory immune response correlating with survival to viral challenge.

Effectiveness and duration of additional immune defense provided by SARS-CoV-2 infection before and after receiving the mRNA COVID-19 vaccine BNT162b2

BackgroundOur investigation focused whether infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) before or after receiving the mRNA COVID-19 vaccine can increase immune protection. And we also investigated relationship of infection acquired. MethodsThree shots of the mRNA coronavirus disease 2019 (COVID-19) vaccine BNT162b2 were administered to 736 healthcare workers at Tokyo Shinagawa Hospital. Serum samples were collected before the first shot (P1), at one month (P2), and at six months (P3) after the second shot and at one month after the third shot (P4). The presence of infection was assessed using IgG against the nucleocapsid (IgG (N) and RBD in the spike protein of SARS-CoV-2. We defined infection before P2 as natural infection (NI) and infection between P2 and P3 as breakthrough infection (BI) and compared susceptibility to further infection between the NI (−) and NI (+) groups and between BI (−) and BI (+) groups. Events in 485 participants who had a complete dataset of IgG (N) and IgG (RBD) from P1 to P4 were analyzed. ResultsThe presence of SARS-CoV-2 infection before P2 were examined by examining the titers of IgG (N)P1, IgG (N) P2, and IgG (RBD) P1 that exceeded the cutoff values. Consequently, 35 participants (7.22 %) were categorized into the NI (+) group, whereas 450 (92.8 %) were categorized into the NI (−) group. Between P2 and P3, the NI (−) group showed a higher rate of SARS-CoV-2 infection than the NI (+) group; however, there was no significant difference in the infection rate between P3 and P4. The infection rate was significantly lower in the BI (+) group than in the BI (−) group. Pre-primary vaccination infection significantly increased IgG (RBD) levels between P1 and P3. Post-primary vaccination infection significantly increased IgG (RBD) levels between P3 and P4. ConclusionsInfection with SARS-CoV-2 before or after receiving the mRNA COVID-19 vaccine can increase immune protection; however, the duration of this effect may be limited.

Antibody-mediated immunological memory correlates with long-term Lyme veterinary vaccine protection in mice

Lyme disease, caused by the bacterium Borrelia burgdorferi, is the most common tick-borne illness in the United States. Despite the rise in Lyme disease incidence, there is no vaccine against B. burgdorferi approved for human use. Little is known about the immune correlates of protection needed to prevent Lyme disease. In this work, a mouse model was used to characterize the immune response and compare the protection provided by two USDA-approved vaccines for use in canines: Duramune (bacterin vaccine) and Vanguard crLyme (subunit vaccine composed of two outer surface proteins, OspA and OspC). C3H/HeNCrl mice were immunized with two doses of either Duramune or Vanguard, and immune responses and protection against B. burgdorferi were assessed in short (35 days) and long-term (120 days) studies. Flow cytometry, ELISPOT detection of antibody-producing cells, and antibody affinity studies were performed to identify correlates of vaccine-mediated protection. Both vaccines induced humoral responses, with high IgG titers against B. burgdorferi. However, the levels of anti-B. burgdorferi antibodies decayed over time in Vanguard-vaccinated mice. While both vaccines triggered the production of antibodies against both OspA and OspC, antibody levels against these proteins were also lower in Vanguard-vaccinated mice 120 days post-vaccination. Both vaccines only provided partial protection against B. burgdorferi at the dose used in this model. The protection provided by Duramune was superior to Vanguard 120 days post-vaccination, and was characterized by higher antibody titers, higher abundance of long-lived plasma cells, and higher avidity antibodies than Vanguard. Overall, these studies provide insights into the importance of the humoral memory response to veterinary vaccines against Lyme disease and will help inform the development of future human vaccines.

Age differentially impacts adaptive immune responses induced by adenoviral versus mRNA vaccines against COVID-19.

Adenoviral and mRNA vaccines encoding the viral spike (S) protein have been deployed globally to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Older individuals are particularly vulnerable to severe infection, probably reflecting age-related changes in the immune system, which can also compromise vaccine efficacy. It is nonetheless unclear to what extent different vaccine platforms are impacted by immunosenescence. Here, we evaluated S protein-specific immune responses elicited by vaccination with two doses of BNT162b2 or ChAdOx1-S and subsequently boosted with a single dose of BNT162b2 or mRNA-1273, comparing age-stratified participants with no evidence of previous infection with SARS-CoV-2. We found that aging profoundly compromised S protein-specific IgG titers and further limited S protein-specific CD4+ and CD8+ T cell immunity as a probable function of progressive erosion of the naive lymphocyte pool in individuals vaccinated initially with BNT162b2. Our results demonstrate that primary vaccination with ChAdOx1-S and subsequent boosting with BNT162b2 or mRNA-1273 promotes sustained immunological memory in older adults and potentially confers optimal protection against coronavirus disease 2019.

Serological responses to COVID-19 vaccination in patients with chronic liver diseases

Longitudinal analysis of antibody responses following three-dose COVID-19 vaccination in patients with chronic liver disease (CLD) has been limited. From August 2021 to February 2023, sequential anti-SARS-CoV-2 spike IgG titers were determined in 45 patients with CLD who received two or three doses of COVID-19 vaccine. The geometric mean of anti-spike IgG at four weeks after the second and third doses were 1313.16 BAU/mL and 3042.29 BAU/mL, respectively, and it decreased significantly from four to 24 weeks after the second (1313.16 vs. 198.42 BAU/mL, p = 0.002) and the third (3042.29 vs. 636.71 BAU/mL, p < 0.001) dose. The anti-spike IgG titers in participants receiving prime-boost homologous mRNA vaccines (BNT162b2 or mRNA-1273) were comparable between participants with and those without significant liver fibrosis at each follow-up time point. This study demonstrated a notable decrease in anti-spike IgG after completion of the vaccination schedule in patients with CLD, highlighting the importance of additional booster doses.

Silicon or Calcium Doping Coordinates the Immunostimulatory Effects of Aluminum Oxyhydroxide Nanoadjuvants in Prophylactic Vaccines.

Aluminum salts still remain as the most popular adjuvants in marketed human prophylactic vaccines due to their capability to trigger humoral immune responses with a good safety record. However, insufficient induction of cellular immune responses limits their further applications. In this study, we prepare a library of silicon (Si)- or calcium (Ca)-doped aluminum oxyhydroxide (AlOOH) nanoadjuvants. They exhibit well-controlled physicochemical properties, and the dopants are homogeneously distributed in nanoadjuvants. By using Hepatitis B surface antigen (HBsAg) as the model antigen, doped AlOOH nanoadjuvants mediate higher antigen uptake and promote lysosome escape of HBsAg through lysosomal rupture induced by the dissolution of the dopant in the lysosomes in bone marrow-derived dendritic cells (BMDCs). Additionally, doped nanoadjuvants trigger higher antigen accumulation and immune cell activation in draining lymph nodes. In HBsAg and varicella-zoster virus glycoprotein E (gE) vaccination models, doped nanoadjuvants induce high IgG titer, activations of CD4+ and CD8+ T cells, cytotoxic T lymphocytes, and generations of effector memory T cells. Doping of aluminum salt-based adjuvants with biological safety profiles and immunostimulating capability is a potential strategy to mediate robust humoral and cellular immunity. It potentiates the applications of engineered adjuvants in the development of vaccines with coordinated immune responses.

Variant-specific antibody response following repeated SARS-CoV-2 vaccination and infection

The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.

Lower Humoral and Cellular Immunity Following Asymptomatic SARS-CoV-2 Infection Compared to Symptomatic Infection in Education (The ACE Cohort)

PurposeAsymptomatic SARS-CoV-2 infections were widely reported during the COVID-19 pandemic, acting as a hidden source of infection. Many existing studies investigating asymptomatic immunity failed to recruit true asymptomatic individuals. Thus, we conducted a longitudinal cohort study to evaluate humoral- and cell-mediated responses to infection and vaccination in well-defined asymptomatic young adults (the Asymptomatic COVID-19 in Education [ACE] cohort).MethodsAsymptomatic testing services located at three UK universities identified asymptomatic young adults who were subsequently recruited with age- and sex-matched symptomatic and uninfected controls. Blood and saliva samples were collected after SARS-CoV-2 Wuhan infection, and again after vaccination. 51 participant’s anti-spike antibody titres, neutralizing antibodies, and spike-specific T-cell responses were measured, against both Wuhan and Omicron B.1.1.529.1.ResultsAsymptomatic participants exhibited reduced Wuhan-specific neutralization antibodies pre- and post-vaccination, as well as fewer Omicron-specific neutralization antibodies post-vaccination, compared to symptomatic participants. Lower Wuhan and Omicron-specific IgG titres in asymptomatic individuals were also observed pre- and post-vaccination, compared to symptomatic participants. There were no differences in salivary IgA levels. Conventional flow cytometry analysis and multi-dimensional clustering analysis indicated unvaccinated asymptomatic participants had significantly fewer Wuhan-specific IL-2 secreting CD4+ CD45RA+ T cells and activated CD8+ T cells than symptomatic participants, though these differences dissipated after vaccination.ConclusionsAsymptomatic infection results in decreased antibody and T cell responses to further exposure to SARS-CoV-2 variants, compared to symptomatic infection. Post-vaccination, antibody responses are still inferior, but T cell immunity increases to match symptomatic subjects, emphasising the importance of vaccination to help protect asymptomatic individuals against future variants.

Immune response against the SARS-CoV-2 spike protein in cancer patients after COVID-19 vaccination during the Omicron wave: a prospective study

BackgroundCancer patients often have weakened immune systems, resulting in a lower response to vaccines, especially those receiving immunosuppressive oncological treatment (OT). We aimed to assess the impact of OT on the humoral and T-cell response to the B.1 lineage and Omicron variant following COVID-19 vaccination in patients with solid and hematological neoplasms. MethodsWe conducted a prospective study on cancer patients, stratified into OT and non-OT groups, who received a two-dose series of the COVID-19 mRNA vaccine and a booster six months later. The outcomes measured were the humoral (anti-SARS-CoV-2 S IgG titers and ACE2-S interaction inhibition capacity) and cellular (SARS-CoV-2 S-specific T-cell spots per million PBMCs) responses against the B.1 lineage and Omicron variant. These responses were evaluated four weeks after the second dose (n = 98) and eight weeks after the booster dose (n = 71). ResultsThe humoral response after the second vaccine dose against the B.1 lineage and Omicron variant was significantly weaker in the OT group compared to the non-OT group (q-value<0.05). A booster dose of the mRNA-1273 vaccine significantly improved the humoral response in the OT group, making it comparable to the non-OT group. The mRNA-1273 vaccine, designed for the original Wuhan strain, elicited a weaker humoral response against the Omicron variant compared to the B.1 lineage, regardless of oncological treatment or vaccine dose. In contrast, T-cell responses against SARS-CoV-2, including the Omicron variant, were already present after the second vaccine dose and were not significantly affected by oncological treatments. ConclusionsCancer patients, particularly those receiving immunosuppressive oncological treatments, should require booster doses and adapted COVID-19 vaccines for new SARS-CoV-2 variants like Omicron. Future studies should evaluate the durability of the immune response and the efficacy of individualized regimens.