IgG Titers Research Articles

Navigating the Landscape of B Cell Mediated Immunity and Antibody Monitoring in SARS-CoV-2 Vaccine Efficacy: Tools, Strategies and Clinical Trial Insights

Correlates of Protection (CoP) are biomarkers above a defined threshold that can replace clinical outcomes as primary endpoints, predicting vaccine effectiveness to support the approval of new vaccines or follow up studies. In the context of COVID-19 vaccination, CoPs can help address challenges such as demonstrating vaccine effectiveness in special populations, against emerging SARS-CoV-2 variants or determining the durability of vaccine-elicited immunity. While anti-spike IgG titres and viral neutralising capacity have been characterised as CoPs for COVID-19 vaccination, the contribution of other components of the humoral immune response to immediate and long-term protective immunity is less well characterised. This review examines the evidence supporting the use of CoPs in COVID-19 clinical vaccine trials, and how they can be used to define a protective threshold of immunity. It also highlights alternative humoral immune biomarkers, including Fc effector function, mucosal immunity, and the generation of long-lived plasma and memory B cells and discuss how these can be applied to clinical studies and the tools available to study them.

Rotavirus-Specific Maternal Serum Antibodies and Vaccine Responses to RV3-BB Rotavirus Vaccine Administered in a Neonatal or Infant Schedule in Malawi.

High titres of rotavirus-specific maternal antibodies may contribute to lower rotavirus vaccine efficacy in low- and middle-income countries (LMICs). RV3-BB vaccine (G3P[6]) is based on a neonatal rotavirus strain that replicates well in the newborn gut in the presence of breast milk. This study investigated the association between maternal serum antibodies and vaccine response in infants administered the RV3-BB vaccine. Serum was collected antenatally from mothers of 561 infants enrolled in the RV3-BB Phase II study conducted in Blantyre, Malawi, and analysed for rotavirus-specific serum IgA and IgG antibodies using enzyme-linked immunosorbent assay. Infant vaccine take was defined as cumulative IgA seroconversion (≥3 fold increase) and/or stool vaccine shedding. Maternal IgA or IgG antibody titres did not have a negative impact on vaccine-like stool shedding at any timepoint. Maternal IgG (but not IgA) titres were associated with reduced take post dose 1 (p < 0.005) and 3 (p < 0.05) in the neonatal vaccine schedule group but not at study completion (week 18). In LMICs where high maternal antibodies are associated with low rotavirus vaccine efficacy, RV3-BB in a neonatal or infant vaccine schedule has the potential to provide protection against severe rotavirus disease.

Immune Response after Vaccination against Tick-Borne Encephalitis Virus (TBEV) in Horses.

(1) Background: Horses infected by a tick-borne encephalitis virus (TBEV) can develop clinically apparent infections. In humans, vaccination is the most effective preventive measure, while a vaccine is not available for horses. The objective of this study was to describe the immune response in horses after a TBEV vaccination with a human vaccine. (2) Materials and Methods: Seven healthy horses were randomised to a treatment or a control group in a stratified fashion based on TBEV-IgG concentrations on day -4. The treatment group (n = 4) was intramuscularly vaccinated using an inactivated human TBEV vaccine on days 0 and 28; the control group (n = 3) did not receive an injection. A clinical examination and blood sampling were performed on day -4, 0, 2, 4, 6, 8, 10, 14, 28, 30, 32, 34, 36, 38, 43, 56, 84, and 373. A linear mixed model analysis was used to compare IgG and IgM concentrations, neutralising antibody (nAb) titres, leucocyte count, serum amyloid A (SAA), and fibrinogen and globulin concentrations between the groups and time points. (3) Results: The clinical examination was normal in all horses at all time points. There were no significant changes in SAA, globulin, and fibrinogen concentrations and leucocyte count between the groups or time points (all p > 0.05). There was no significant increase in IgG, IgM, or nAb titres in the control group over time (all p > 0.05). In the vaccination group, there was a significant increase in IgG concentration and nAb titres after the second vaccination (p < 0.0001). There was no significant increase in IgM antibodies after the TBEV vaccination (all p > 0.05). One horse in the vaccination group had an IgM concentration above the laboratory reference on day 10. (4) Conclusions: The human TBEV vaccine did not have side effects when used in healthy horses in this study. A significant rise in TBEV-specific IgG antibodies and nAbs after the second vaccination was observed. However, IgG and nAb titres have been shown to decrease within 1 year after vaccination. The results of this study indicate that a vaccination with a human vaccine only induces a mild rise in IgM antibodies and only in previously naive horses. With no significant changes to inflammatory parameters in the vaccinated horses, it remains unclear whether vaccination with the human vaccine leads to protective immunity.

Oral Chagas disease outbreak by bacaba juice ingestion: A century after Carlos Chagas' discovery, the disease is still hard to manage.

Orally transmitted acute Chagas disease (ACD) primarily affects low-visibility and low-income individuals in tropical and subtropical zones. Managing ACD remains challenging even after more than 100 years of its discovery. Its spread to non-endemic areas has made it a global health issue. The aim of this work is to demonstrate the difficulties encountered in handling a real-life situation. This report examines an outbreak of 39 cases of ACD due to oral transmission by bacaba juice ingestion that occurred in Pedro do Rosário, Maranhão, Brazil. A clinical and epidemiological investigation, including an entomological search, was conducted. Diagnosis criteria included positive peripheral blood smear (PBS), seroconversion of IgG, and a two-fold increase in IgG titer (laboratory criteria); and clinical findings, epidemiological exposure, and at least one positive IgG test (clinical-epidemiological criteria). In-house conventional polymerase chain reaction (PCR) was performed on 33 samples. All patients were treated with benznidazole. After 4.5 years, IgG levels were reassessed in 26 individuals. The mean age was 33.6 years, with no gender difference. The mean incubation period was 13.8 days, and the mean between symptom onset and treatment was 16.6 days. The most common symptoms were fever and lymphadenopathy (90%). Diagnostic success rates were 66.6% (laboratory criteria), 23% (clinical-epidemiological criteria), and 10.2% (high clinical suspicion despite negative tests). Test positivity rates were 69.7% (PBS), 91.4% (serology), and 100% (PCR). There were no deaths. Serological cure was achieved in 34.6% of cases, and IgG titers decreased in 15.3%. We encountered several barriers in managing ACD, including population vulnerability, reliance on outdated diagnostic techniques, lack of standardized molecular biology methods, and limited therapeutic options. This report underscores the importance of rapid surveillance and early treatment to prevent fatalities. We recommend the standardization of conventional PCR in diagnostic routines.

Host heterogeneity in humoral bactericidal activity can be complement independent.

Humoral bactericidal activity was first recognized nearly a century ago. However, the extent of inter-individual heterogeneity and the mechanisms underlying such heterogeneity beyond antibody or complement systems have not been well studied. The plasma bactericidal activity of five healthy volunteers were tested against 30 strains of Gram-negative uropathogens, Klebsiella pneumoniae and Escherichia coli, associated with bloodstream infections. IgG and IgM titers specific to K. pneumoniae strains KP13883 and KPB1 were measured by ELISA, and complement inhibitor was used to measure the contribution of complement-induced killing. Furthermore, MALDI-TOF mass spectrometry was conducted to determine the metabolomic components of plasma with bactericidal properties in 25 healthy individuals using Bayesian inference of Pearson correlation between peak intensity and colony counts of surviving bacteria. Plasma bactericidal activity varied widely between individuals against various bacterial strains. While individual plasma with higher IgM titers specific to K. pneumoniae strain KP13883 showed more efficient killing of the strain, both IgM and IgG titers for K. pneumoniae strain KPB1 did not correlate well with the killing activity. Complement inhibition assays elucidated that the complement-mediated killing was not responsible for the inter-individual heterogeneity in either isolate. Subsequently, using MALDI-TOF mass spectrometry on plasmas of 25 healthy individuals, we identified several small molecules including gangliosides, pediocins, or saponins as candidates that showed negative correlation between peak intensities and colony forming units of the test bacteria. This is the first study to demonstrate the inter-individual heterogeneity of constitutive innate humoral bactericidal function quantitatively and that the heterogeneity can be independent of antibody or the complement system.

The Escherichia coli TolC efflux pump protein is immunogenic and elicits protective antibodies.

Antimicrobial resistance is an increasing worldwide public health burden that threatens to make existent antimicrobials obsolete. An important mechanism of antimicrobial resistance is the overexpression of efflux pumps, which reduce the intracellular concentration of antimicrobials. TolC is the outer membrane protein of an efflux pump that has gained attention as a therapeutic target. Little is known about the immune response against TolC. Here we evaluated the immune response against TolC from Escherichia coli. TolC in silico epitope prediction showed several residues that could bind to human antibodies, and we showed that human plasma presented higher titers of anti-TolC IgG and IgA, than IgM. E. coli recombinant TolC protein stimulated macrophages in vitro to produce nitric oxide, as well as IL-6 and TNF-α, assessed by Griess assay and ELISA, respectively. Immunization of mice with TolC intraperitoneally and an in vitro re-stimulation led to increased T cell proliferation and IFNγ production, evaluated by flow cytometry and ELISA, respectively. TolC mouse immunization stimulated anti-TolC IgM and IgG production, with higher levels of IgG1 and IgG2, amongst the IgG subclasses. Anti-TolC murine antibodies could bind to live E. coli and increase bacterial uptake and elimination by macrophages in vitro. Intraperitoneal or intranasal, but not oral, immunizations with inactivated E. coli also led to anti-TolC antibody production. Finally, TolC immunization increased mouse survival rates to antimicrobial-sensitive or resistant E. coli infection. Our results showed that TolC is immunogenic, leading to the production of protective antibodies against E. coli, reinforcing its value as a therapeutic target.

Adenovirus-Mediated Expression of Dengue Virus 2 Envelope Ferritin Nanoparticles Induced Virus-Specific Immune Responses in BALB/c Mice

This study provides a preliminary background for the development of a viral vector vaccine for the dengue virus using genetic material encoded by dengue envelope ferritin nanoparticles. Adenoviruses were generated for the recombinant envelope of dengue virus 2 (DENV2) and the envelope human ferritin heavy chain using a two-vector adenovirus system. The primary immunostimulatory activity of the two viruses was analyzed in mice to determine the effect of envelope ferritin nanoparticles. Transfection of a shuttle vector delivered the target gene and packaging vector carrying the packaging signal, and recombinant adenoviruses (rAds) were generated and purified using an ultracentrifugation method. Transduction efficiencies of the generated adenoviruses were confirmed in A549 cells. Purified adenoviruses (8 × 106 PFU/mL) were immunized intramuscularly into 6 weeks old BALB/c mice. Subsequently, the DENV2-specific IgG titer was evaluated 1 and 4 weeks after immunization. Envelope ferritin-immunized mice showed a significant IgG response compared to envelope-only immunized mice at 1 and 4 weeks after immunization, revealing the persistence of the dengue virus-specific IgG response. This method demonstrated the capability of the viral vector vaccine to be used as a carrier for ferritin nanoparticles, instead of direct immunization with ferritin nanoparticles.

Intranasal Self-Adjuvanted Lipopeptide Vaccines Elicit High Antibody Titers and Strong Cellular Responses against SARS-CoV-2.

Despite concerted efforts to tackle the COVID-19 pandemic, the persistent transmission of SARS-CoV-2 demands continued research into novel vaccination strategies to combat the virus. In light of this, intranasally administered peptide vaccines, particularly those conjugated to an immune adjuvant to afford so-called "self-adjuvanted vaccines", remain underexplored. Here, we describe the synthesis and immunological evaluation of self-adjuvanting peptide vaccines derived from epitopes of the spike glycoprotein of SARS-CoV-2 covalently fused to the potent adjuvant, Pam2Cys, that targets toll-like receptor 2 (TLR2). When administered intranasally, these vaccines elicited a strong antigen-specific CD4+ and CD8+ T-cell response in the lungs as well as high titers of IgG and IgA specific to the native spike protein of SARS-CoV-2. Unfortunately, serum and lung fluid from mice immunized with these vaccines failed to inhibit viral entry in spike-expressing pseudovirus assays. Following this, we designed and synthesized fusion vaccines composed of the T-cell epitope discovered in this work, covalently fused to epitopes of the receptor-binding domain of the spike protein reported to be neutralizing. While antibodies elicited against these fusion vaccines were not neutralizing, the T-cell epitope retained its ability to stimulate strong antigen-specific CD4+ lymphocyte responses within the lungs. Given the Spike(883-909) region is still completely conserved in SARS-CoV-2 variants of concern and variants of interest, we envision the self-adjuvanting vaccine platform reported here may inform future vaccine efforts.

The Improvement of Adaptive Immune Responses towards COVID-19 Following Diphtheria-Tetanus-Pertussis and SARS-CoV-2 Vaccinations in Indonesian Children: Exploring the Roles of Heterologous Immunity.

Routine childhood vaccination, e.g., for diphtheria, tetanus, and pertussis (DTP), might provide additional protection against SARS-CoV-2 infection. This concept of heterologous immunity was explored in healthy children receiving both DTP and inactivated SARS-CoV-2 vaccines. A cross-sectional study was performed on 154 healthy children aged 6-8 years old in Jakarta, Indonesia. Their vaccination status for the DTP (including a diphtheria-tetanus booster vaccine at 5 years old) and CoronaVac (from 6 years old) vaccines were recorded. Peripheral blood samples were collected from all participants, in which anti-diphtheria toxoid IgG and anti-SARS-CoV-2 S-RBD antibodies and T cell-derived IFN-γ were measured. The study participants with complete DTP vaccination had significantly higher titers of anti-diphtheria toxoid IgG than the ones without (median = 0.9349 versus 0.2113 IU/mL; p < 0.0001). Upon stratification based on DTP and CoronaVac vaccination statuses, the participants with complete DTP and CoronaVac vaccinations had the highest titer of anti-SARS-CoV-2 S-RBD antibodies (median = 1196 U/mL) and the highest concentration of SARS-CoV-2-specific T cell-derived IFN-γ (median = 560.9 mIU/mL) among all the groups. Healthy children aged 6-8 years old with complete DTP and CoronaVac vaccinations exhibited stronger SARS-CoV-2-specific T cell immune responses. This might suggest an additional benefit of routine childhood vaccination in generating protection against novel pathogens, presumably via heterologous immunity.

IgG Subtype Response against Virulence-Associated Protein A in Foals Naturally Infected with Rhodococcus equi.

Rhodococcus equi is an intracellular bacterium that causes suppurative pneumonia in foals. T-helper (Th) 1 cells play an important role in the protective response against R. equi. In mice and humans, the directionality of IgG switching reflects the polarization of Th-cell responses, but this has not been fully elucidated in horses. In this 4-year study, we classified R. equi-infected foals into surviving and non-surviving group and investigated differences in IgG subclass response to virulence-associated protein A, the main virulence factor of R. equi, between the groups. IgGa, IgGb, and IgG(T) titers were significantly higher in the non-surviving group compared with the surviving group. The titers of IgGa and IgG(T), IgGb and IgG(T), and IgGa and IgGb, respectively, were positively correlated, and the IgG(T)/IgGb ratio in the non-surviving group was significantly higher than that in the surviving group. The IgG(T) titer tended to increase more than the IgGa and IgGb titers in the non-surviving group compared with the surviving group. Our findings suggest that the IgG(T) bias in IgG subclass responses reflects the immune status, which exacerbates R. equi infection.

FcRider: a recombinant Fc nanoparticle with endogenous adjuvant activities for hybrid immunization.

Active immunization (vaccination) induces long-lasting immunity with memory, which takes weeks to months to develop. Passive immunization (transfer of neutralizing antibodies) provides immediate protection, yet with high cost and effects being comparatively short-lived. No currently approved adjuvants are compatible with formulations to combine active and passive immunizations, not to mention their huge disparities in administration routes and dosage. To solve this, we engineered the Fc fragment of human IgG1 into a hexamer nanoparticle and expressed its afucosylated form in Fut8-/- CHO cells, naming it "FcRider." FcRider is highly soluble with long-term stability, easily produced at high levels equivalent to those of therapeutic antibodies, and is amenable to conventional antibody purification schemes. Most importantly, FcRider possesses endogenous adjuvant activities. Using SWHEL B cell receptor (BCR) transgenic mice, we found that HEL-FcRider induced GL7+ germinal center B cells and HEL-specific IgG. Similarly, immunizing mice with UFO-BG-FcRider, a fusion containing the stabilized human immunodeficiency virus-1 (HIV-1) Env protein as immunogen, promoted somatic hypermutation and generation of long CDR3 of the IgG heavy chains. Intramuscular injection of (Fba+Met6)3-FcRider, a fusion with two peptide epitopes from Candida albicans cell surface, stimulated strong antigen-specific IgG titers. In three different models, we showed that afucosylated FcRider functions as a multivalent immunogen displayer and stimulates antigen-specific B cells without any exogenous adjuvant. As an antibody derivative, afucosylated FcRider could be a novel platform combining vaccines and therapeutic antibodies, integrating active and passive immunizations into single-modality "hybrid immunization" to provide complete and long-lasting protection against infections, and may open new avenues in cancer immunotherapy as well.

Safety and Immunogenicity of the Intranasal Vaccine Candidate Mambisa and the Intramuscular Vaccine Abdala Used as Booster Doses for COVID-19 Convalescents: A Randomized Phase 1-2 Clinical Trial.

A phase 1-2, prospective, multicenter, randomized, open-label clinical trial (Code RPCEC00000382), with parallel groups, involving 1161 participants, was designed to assess the safety and immunogenicity of two Cuban COVID-19 vaccines (Mambisa and Abdala) in boosting COVID-19 immunity of convalescent adults after receiving one dose of either vaccine. The main safety outcome was severe vaccination adverse events occurring in <5% of vaccinees. Main immunogenicity success endpoints were a ≥4-fold anti-RBD IgG seroconversion or a ≥20% increase in ACE2-RBD inhibitory antibodies in >55% of vaccinees in Phase 1 and >70% in Phase 2. Neutralizing antibody titers against SARS-CoV-2 variants were evaluated. Both vaccines were safe-no deaths or severe adverse events occurred. Mild intensity adverse events were the most frequent (>73%); headaches predominated for both vaccines. Phase 1 responders were 83.3% (p = 0.0018) for Abdala. Mambisa showed similar results. Phase 2 responders were 88.6% for Abdala (p < 0.0001) and 74.2% for Mambisa (p = 0.0412). In both phases, anti-RBD IgG titers, inhibition percentages and neutralizing antibody titers increased significantly after the booster dose. Both vaccines were safe and their immunogenicity surpassed the study endpoints.

A Correlation Study to Comprehend the SAR-CoV-2 Viral Load, Antiviral Antibody Titer, and Severity of COVID-19 Symptoms Post-infection Amongst the Vaccinated Population in Kamrup District of As sam, Northeast India.

As per the recommendation of the United States Food and Drug Administration, more research is needed to determine the antibody titer against COVID-19 vaccination. The study aimed to understand the relationship between the antibody titer to the demographics, infection severity, and cycle threshold (CT) values of confirmed COVID-19 patients. Initially, we obtained consent from 185 populations and included sixty RT-PCRpositive COVID-19 patients from Kamrup District in the Northeast State of Assam, India. The vaccination status was recorded and tested for the level of serum immunoglobulin (IgG). The CT values, gender, and clinical symptoms-based scoring (CSBS) correlated with their IgG value. Around 48% of participants gained an antibody titer more than the threshold value and showed CT values between 18-25. Moreover, the maximum distributed score above the average was found between the CT values 18-25. The IgG titer value differs significantly amongst the vaccinated population, which may depend upon their genetic and demographic variability.

Vaccination with OprB porin, and its epitopes offers protection against A. baumannii infections in mice

A. baumannii is a deadly antimicrobial resistance pathogen that acquires drug resistance through different mechanisms. Therefore, it is necessary to investigate all its virulence factors and design effective vaccines against it. For this purpose, OprB, an outer membrane porin, was investigated in this study, and its secondary and tertiary structures, physicochemical properties, and B-T epitopes were determined. The vaccine potential of this protein and its linear, non-continuous, and chimeric epitopes were also in-vivo analyzed. Based on the results, two surface epitopes and one non-continuous epitope were identified. Surface contiguous epitopes were produced recombinantly and non-continuous epitope sequences were synthesized and then produced. The chimeric epitope was also produced via the SOE-PCR technique. Active and passive immunization of mice with the whole OprB protein, non-continuous epitope, contiguous epitopes, two epitopes in chimeric form, as well as the mixture of two purified epitopes showed that the survival level and total IgG titer of the mice compared to non-vaccinated mice or mice that were vaccinated with an internal fragment increased significantly. The bacterial load in the immunized mice’s lung, liver, kidney, and spleen was much lower than in the control groups, and the TNF-α, IFN-γ, and IL-6 cytokines levels were also lower in these groups and were similar to the naive mice. On the other hand, subunit vaccines showed acceptable safety and due to their minimal cross-activity, their use is much safer.

Maternal Immunization with Adjuvanted Recombinant Receptor-Binding Domain Protein Provides Immune Protection against SARS-CoV-2 in Infant Monkeys.

Maternal vaccinations administered prior to conception or during pregnancy enhance the immune protection of newborn infants against many pathogens. A feasibility experiment was conducted to determine if monkeys can be used to model the placental transfer of maternal antibody against SARS-CoV-2. Six adult rhesus monkeys were immunized with adjuvanted recombinant-protein antigens comprised of receptor-binding domain human IgG1-Fc fusion proteins (RBD-Fc) containing protein sequences from the ancestral-Wuhan or Gamma variants. The female monkeys mounted robust and sustained anti-SARS-CoV-2 antibody responses. Blood samples collected from their infants after delivery verified prenatal transfer of high levels of spike-specific IgG, which were positively correlated with maternal IgG titers at term. In addition, an in vitro test of ACE2 neutralization indicated that the infants' IgG demonstrated antigen specificity, reflecting prior maternal immunization with either Wuhan or Gamma-variant antigens. All sera showed stronger ACE2-RBD binding inhibition when variants in the assay more closely resembled the vaccine RBD sequence than with more distantly related variants (i.e., Delta and Omicron). Monkeys are a valuable animal model for evaluating new vaccines that can promote maternal and infant health. Further, the findings highlight the enduring nature and safety of the immune protection elicited by an adjuvanted recombinant RBD-Fc vaccine.

Humoral immunity and safety of respiratory virus vaccines in systemic lupus erythematosus population: a meta-analysis based on twenty-five observational studies

Background Systemic lupus erythematosus (SLE), an extensive autoimmune disorder, compromises viral resistance and alters immune responses post respiratory virus vaccines. This study aims to assess immune response levels and safety in SLE patients following respiratory virus vaccines. Methods Extensive searches, until 1 March 2024, were conducted using PubMed, EMBASE, and Cochrane Library. Outcomes, encompassing seroconversion rate (SCR), antibody and IgG titers, neutralizing antibodies, anti-spike antibodies, anti-receptor binding domain (RBD) IgG, and adverse events, were appraised. Results Sixteen articles, comprising 25 observational studies, were included. SLE patients exhibited lower SCR (OR = 0.42, 95%CI: 0.26 to 0.69), antibody titers (SMD=-2.84, 95%CI: −3.36 to −1.61), and neutralizing antibodies (OR = 0.27, 95%CI: 0.13 to 0.56) compared to the healthy population post respiratory virus vaccines. Notably, differences were statistically insignificant for anti-RBD IgG (OR = 1.75, 95%CI: 0.10 to 29.42), IgG titers (SMD=-2.54, 95%CI: −5.57 to −0.49), anti-spike antibodies (OR = 0.35, 95%CI: 0.08 to 1.53), injection site discomfort (OR = 1.03, 95%CI: 0.52 to 2.06), fatigue (OR = 1.23, 95%CI: 0.74 to 2.03), fever (OR = 1.02, 95%CI: 0.64 to 1.63), localized reactions (OR = 0.69, 95%CI: 0.37 to 1.30), systemic reactions (OR = 1.00, 95%CI: 0.59 to 1.69), allergic reactions (OR = 5.11, 95%CI: 0.24 to 107.10), self-reported vaccination-related adverse events (OR = 1.61, 95%CI: 0.56 to 4.63), and disease flares after vaccination (OR = 1.00, 95%CI: 0.14 to 7.28). Conclusion Despite the reduced immune response and host protection in SLE patients post-Corona Virus Disease 2019 (COVID-19) and influenza vaccines compared to the healthy population, safety profiles are comparable. Therefore, it is recommended that SLE patients receive COVID-19 and influenza viral vaccines to fortify their resistance.

Preclinical Evidence for the Protective Capacity of Antibodies Induced by Lyme Vaccine Candidate VLA15 in People.

Vaccine candidate VLA15 is designed to protect against the dominant Borrelia genospecies-causing Lyme disease in North America and Europe. Active immunization with VLA15 has protected in the mouse model of tick challenge. VLA15 is currently under evaluation in clinical studies for the prevention of Lyme borreliosis. Mice were passively administered sera from clinical trial participants vaccinated with VLA15, or normal human serum from unvaccinated individuals as control. Posttransfer serum anti-outer surface protein A (OspA) immunoglobulin G titers were assessed by enzyme-linked immunosorbent assay. Following passive transfer, mice were challenged with Ixodes ticks colonized with Borrelia burgdorferi (OspA serotype 1) or Borrelia afzelii (OspA serotype 2) and infection was determined by serology for VlsE C6 or by polymerase chain reaction and culture to assess the presence of Borrelia bacteria. Passive transfer of immune sera prevented transmission of Borrelia from the tick vector and protected mice against challenge. Posttransfer protective threshold immunoglobulin G antibody titers were observed in this animal model of 131 U/mL for B burgdorferi (OspA serotype 1) and 352 U/mL for B afzelii (serotype 2). Passive transfer of sera from trial participants immunized with VLA15 protected mice from borreliosis in a tick challenge model. This indicates that VLA15 induces functional immune responses in people that can be linked to efficacy in a stringent preclinical model.

Triple Combinations of AAV9-Vectors Encoding Anti-HIV bNAbs Provide Long-Term In Vivo Expression of Human IgG Effectively Neutralizing Pseudoviruses from HIV-1 Global Panel.

Anti-human immunodeficiency virus (HIV) broadly neutralizing antibodies (bNAbs) offer a promising approach for the treatment of HIV-1. The current paradigm for antibody therapy involves passive antibody transfer, requiring regular delivery of bNAbs in treating chronic diseases such as HIV-1. An alternative strategy is to use AAV-mediated gene transfer to enable in vivo production of desirable anti-HIV-1 antibodies. In this study, we investigated two sets of triple combinations of AAV9-vectors encoding different bNAbs: N6, 10E8, 10-1074 (CombiMab1), and VRC07-523, PGDM1400, 10-1074 (CombiMab2). We used CBAxC57Bl and C57BL/6 mouse models to characterize rAAV-induced antibody expression and to evaluate the neutralization capacity of mouse sera against a global panel of HIV-1 viral strains. rAAV9-mediated IgG expression varied between bNAb clones and mouse strains, with C57BL/6 mice exhibiting higher bNAb titers following rAAV delivery. Although CombiMab2 treatment elicited a higher IgG titer than CombiMab1, both combinations resulted in neutralization of all the viral strains from the global HIV-1 panel. Our data highlight the potential of AAV vectors as a long-term option for HIV-1 therapy.

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 &lt; 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 &lt; 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 &lt; 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.

Intranasal Delivery of Quillaja brasiliensis Saponin-Based Nanoadjuvants Improve Humoral Immune Response of Influenza Vaccine in Aged Mice.

Increasing the effectiveness of vaccines against respiratory viruses is particularly relevant for the elderly, since they are prone to develop serious infections due to comorbidities and the senescence of the immune system. The addition of saponin-based adjuvants is an interesting strategy to increase the effectiveness of vaccines. We have previously shown that ISCOM matrices from Q. brasiliensis (IMXQB) are a safe and potent adjuvant. In this study, we evaluated the use of IMXQB as an adjuvant for the seasonal trivalent influenza vaccine (TIV) in an aged mice model. Herein, we show that subcutaneous injection of the adjuvanted vaccine promoted higher titers of IgM, IgG (and isotypes), and serum hemagglutination inhibition titers (HAI). Notably, aged mice immunized by intranasal route also produced higher IgG (and isotypes) and IgA titers up to 120 days after priming, as well as demonstrating an improvement in the HAI antibodies against the TIV. Further, experimental infected aged mice treated once with sera from adult naïve mice previously immunized with TIV-IMXQB subcutaneously successfully controlled the infection. Overall, TIV-IMXQB improved the immunogenicity compared to TIV by enhancing systemic and mucosal immunity in old mice conferring a faster recovery after the H1N1pdm09-like virus challenge. Thus, IMXQB nanoparticles may be a promising platform for next-generation viral vaccines.