Vaccine Antibody Research Articles

Risk factors and preventive role of vaccination in adult tetanus fatality: a systematic review of reported cases (1990-2024) and meta-analysis.

This study identifies key risk factors for fatality among adult tetanus patients and assesses the impact of vaccination status and antibody levels on disease severity and outcomes in tetanus cases. Despite widespread vaccination, fatality rates remain high due to diagnostic and management challenges. A meta-analysis of 182 tetanus cases from 36 countries, published since 1990, was conducted. The analysis focused on risk factors such as autonomic dysfunction, opisthotonus, incubation time, diabetes, cardiovascular diseases, and skin infections. Key risk factors for fatality included autonomic dysfunction, opisthotonus, shorter incubation periods, diabetes, cardiovascular diseases, and cutaneous infections. Interestingly, fatalities occurred in patients with antibody levels above the proposed protective threshold, showing that serological evidence of immunity is not absolute. Importantly, patients with a complete vaccination history experienced less severe disease, and no fatalities were observed among those who had received a full course of childhood vaccinations. The findings highlight the importance of maintaining up-to-date vaccination schedules to reduce the severity of disease and improve outcomes in tetanus cases. The results suggest that while immunity may not always prevent infection, prior vaccination significantly mitigates disease severity. Given that immunity may not be entirely protective and up-to-date vaccinations seem to improve the outcomes, prompt diagnosis and effective booster vaccinations are crucial to further reduce mortality in tetanus patients.

Deep mutational scanning of rabies glycoprotein defines mutational constraint and antibody-escape mutations.

Rabies virus causes nearly 60,000 human deaths annually. Antibodies that target the rabies glycoprotein (G) are being developed as post-exposure prophylactics, but mutations in G can render such antibodies ineffective. Here, we use pseudovirus deep mutational scanning to measure how all single amino-acid mutations to G affect cell entry and neutralization by a panel of antibodies. These measurements identify sites critical for rabies G's function, and define constrained regions that are attractive epitopes for clinical antibodies, including at the apex and base of the protein. We provide complete maps of escape mutations for eight monoclonal antibodies, including some in clinical use or development. Escape mutations for most antibodies are present in some natural rabies strains. Overall, this work provides comprehensive information on the functional and antigenic effects of G mutations that can help inform development of stabilized vaccine antigens and antibodies that are resilient to rabies genetic variation.

Impact of Immunosuppressive Therapy, Vaccination, and Monoclonal Antibody Use With Outcomes in Liver and Kidney Transplant Recipients With COVID-19: A Retrospective Study.

Patients who have undergone solid organ transplantation are at an elevated risk of severe coronavirus disease (COVID-19) because of post-transplantation immunosuppressive therapy. However, optimization of vaccination, modification of immunosuppression, and implementation of monoclonal antibody (mAb) therapy in transplant recipients with COVID-19 is uncertain. A retrospective cross-sectional study was conducted on patients who underwent liver or kidney transplants and were diagnosed with COVID-19. The association of several vaccine doses, mycophenolate therapy, and mAB therapy with mortality outcomes after COVID-19 diagnosis (3 and 6 months), hospitalization, and length of hospital stay were assessed. This study included 255 patients with a median age of 59 (23-89) were included. Many COVID-19 vaccine doses were not associated with any outcome; however, patients with a liver transplanted with mycophenolate had higher 3-month (19% vs. 0%; p = 0.02) and 6-month (21% vs. 0%; p = 0.01) mortality rates than those who did not. In addition, transplant recipients who received mAb therapy for COVID-19 were less likely to be hospitalized (37% vs. 68%; p < 0.001). For organ transplant recipients with COVID-19, vaccination alone may not be an optimal strategy for preventing serious outcomes. Rather, the types of organ transplant, immunosuppressive therapy (particularly mycophenolate), and COVID-19 treatment strategy should be synergistically considered to promote an optimal therapeutic dynamic for a vulnerable population.

Investigating the Role of B Cell Receptors in Pathogen Recognition and Immune Response Activation: Implications for Infection Control and Therapeutic Development

B cell receptors (BCRs) are critical components of the adaptive immune system, enabling precise pathogen recognition and the activation of immune responses. This research examines the molecular and genetic mechanisms underlying BCR function, focusing on their role in detecting, binding, and neutralizing infectious agents. By exploring antigen-BCR interactions, we aim to elucidate how BCRs achieve their remarkable specificity and affinity, ultimately shaping the strength and duration of immune responses. Through advanced immunological assays, flow cytometry, and bioinformatics, this study characterizes the diversity of BCR expression across various infectious models. Genetic processes such as somatic hypermutation and clonal selection are analyzed to understand how BCR repertoires adapt to rapidly evolving pathogens. Predictive models developed using machine learning identify biomarkers within BCR pathways, providing insights into acute infections, chronic diseases, and autoimmune conditions. The findings highlight variations in BCR function that influence immune resilience and susceptibility to infections. These insights inform vaccine development, antibody engineering, and therapeutic strategies targeting BCR pathways. This research underscores the potential of BCRs as biomarkers and therapeutic targets, paving the way for innovative approaches in infection control and immune modulation, ultimately advancing precision medicine and adaptive immunity research.

The Impact of Obesity on Influenza Vaccine Immunogenicity and Antibody Transfer to the Infant During Pregnancy.

Influenza vaccination is recommended for pregnant women, offering the dual benefit of protecting pregnant women and their newborn infants against influenza. This study aimed to investigate the impact of body mass index (BMI) on influenza vaccine responses in pregnant women and their newborns. Participants included pregnant women attending the Women's and Children's Hospital in South Australia between 2018 and 2021. Maternal blood samples were collected prior to and at 1 and 6 months post-influenza vaccination to measure antibody responses by hemagglutination inhibition (HI) assay. Cord blood samples were also collected. The percentages of participants achieving HI titre ≥40 were compared between obese and non-obese groups. A total of 73 women were enrolled and received quadrivalent influenza vaccination at a mean age of 32 years (range 21-44 y) and median gestation of 24 weeks (range 11-37 weeks). BMI at vaccination was ≥30 kg/m2 for 21/73 women (29%). Most pregnant women demonstrated antibody titres ≥ 40 to all four influenza vaccine strains at 1 month post-vaccination regardless of BMI category (BMI ≥ 30 kg/m2: 19/20; 95% vs. BMI < 30 kg/m2: 47/49; 96%). At 6 months post-vaccination, 12/17 (71%) obese women compared to 36/43 (84%) non-obese women (p = 0.25) maintained HI titres ≥ 40. Cord blood serology showed HI titres ≥ 40 for 11/17 (65%) infants born to mothers with BMI ≥ 30 compared to 30/35 (86%) infants delivered by mothers with BMI < 30 kg/m2. A high BMI did not impair influenza vaccine antibody responses in pregnant women at 1 month post-vaccination. However, at 6 months post-vaccination, and in the cord blood samples, the percentages maintaining HI titre ≥ 40 were lower for obese women than for non-obese pregnant women.

Evolutionary analysis of Hemagglutinin and neuraminidase gene variation in H1N1 swine influenza virus from vaccine intervention in China

Influenza poses a significant threat to the global economy and health. Inactivated virus vaccines were introduced in China for prevention in 2018. In this study, three pairs of hemagglutinin (HA) and neuraminidase (NA) gene sequences were obtained from three Swine influenza virus (IAV-S) inactivated vaccine strains that were marketed in China in 2018. Phylogenetic analysis was carried out with HA and NA gene sequences to investigate the relationship between vaccine use and virus genetic drift. The findings showed that the evolutionary rate of HA remained relatively stable from 2012 to 2017, with an average genetic distance of approximately 0.020731195. However, following the introduction of the swine influenza vaccine, there was a notable acceleration in the evolutionary rate of HA, accompanied by a significant increase in the genetic distance. In 2018, the value was 0.111750269, while in 2019 it was 0.176389393. In contrast, the evolution of NA was relatively smooth, with an average genetic distance of approximately 0.030386708. Finally, we demonstrated that commercial vaccines are weak neutralizers of wild strains through immunization experiments in animals. Thus, we have reason to believe that mutations in the virus favor virus evasion of vaccine immunity. Our findings suggest that vaccine use may significantly impact the evolution of the influenza virus by potentially stimulating mutations. The selection pressure of vaccine antibodies played a role in regulating the variation of IAV-S-H1N1.

New advances in RSV: Is prevention attainable?

Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infection (LRTI), hospitalization, and mortality in infants and young children globally. The greatest burden of severe disease and mortality occurs in low-middle income countries (LMICs), with large and vulnerable childhood populations. The highest rates of RSV-hospitalization occur in healthy-term infants under 3 months of age. Preterm infants, children with chronic lung disease of prematurity, Down's syndrome, congenital heart disease, or immunodeficiency also have a higher risk of severe RSV-LRTI. Early-life RSV-LRTI has also been associated with chronic sequelae, including recurrent LRTI, recurrent wheezing, asthma, and lung function impairment. A RSV pre-fusion (F) maternal vaccine and long-acting monoclonal antibody (nirsevimab) have been licensed for the prevention of RSV-LRTI in infants and young children. Studies show high efficacy and effectiveness particularly for preventing severe RSV-LRTI. Maternal RSV vaccine given at 24-36 weeks of pregnancy was effective in preventing RSV medically attended LRTI and severe RSV-LRTI through 6 months after birth in a phase 3 study conducted in 18 countries over two RSV seasons. Vaccination was safe with no significant difference in adverse events between infants born to mothers who received RSV preF vaccine compared to placebo. A numerical imbalance in preterm births that occurred predominantly in South Africa, unrelated to vaccine timing or gestational age at vaccination and unassociated with mortality, coincided with COVID-19 delta and omicron waves. Nirsevimab, given as a single dose prior or during the RSV season, had high efficacy in preventing RSV-LRTI hospitalization in infants in preterm and in full-term infants, as well as in young children with underlying conditions through 150 days post administration in phase 2 and 3 trials. High effectiveness against hospitalization or severe disease in infants and in at-risk children up to 2 years of age has also been reported in several countries where implementation has occurred. RSV-LRTI is now a preventable disease in infants and young children. Rapid implementation of these highly effective interventions has occurred in many high-income countries, but access remains very limited in LMICs. Access to such RSV preventive interventions is urgently needed for all children to strengthen child health and promote global equity.

Antibody levels versus vaccination status in the outcome of older adults with COVID-19.

BACKGROUNDDespite the currently prevailing, milder Omicron variant of COVID-19, older adults remain at elevated risk of hospital admission, critical illness, and death. Loss of efficacy of the immune system, including reduced strength, quality, and durability of antibody responses, may render generalized recommendations on booster vaccinations inadequate. There is a lack of data on the efficacy of antibody levels in older adults and on the utility of vaccination status versus antibody levels as a correlate of protection. It is further unclear whether antibody levels may be used to guide the timing of booster vaccinations in older adults.METHODSWe conducted a prospective multicenter cohort study comprising hospitalized patients with COVID-19. Anti-SARS-CoV-2 spike antibodies were measured on hospital admission. The primary endpoint was in-hospital mortality. Patients were stratified by age, antibody levels, and vaccination status. Multiple logistic regression and Cox regression analyses were conducted.RESULTSIn total, 785 older patients (≥60 years of age [a]) and 367 controls (<60a) were included. After adjusting for confounders, risk of mortality, ICU admission, endotracheal intubation, and oxygen administration was 4.9, 2.6, 6.5, and 2.3 times higher, respectively, if antibody levels were < 1,200 BAU/mL (aOR, 4.92 [95%CI, 2.59-9.34], P < 0.0001; aOR, 2.64 [95%CI, 1.52-4.62], P = 0.0006; aOR, 6.50 [95%CI, 1.48-28.47], P = 0.013; aOR, 2.34 [95%CI, 1.60-3.343], P < 0.0001). Older adults infected with the Omicron variant were approximately 6 times more likely to die if antibody levels were < 1,200 BAU/mL (aOR, 6.3 [95% CI, 2.43-16.40], P = 0.0002).CONCLUSIONAntibody levels were a stronger predictor of in-hospital mortality than vaccination status. Monitoring antibody levels may constitute a better and more direct approach for safeguarding older adults from adverse COVID-19 outcomes.

Efficacy Evaluation of COVID-19 Vaccines in Patients with Autoimmune Rheumatic Diseases in Mashhad, Iran

vaccination. However, since the majority of studies in the related literature are focused on the efficacy of messenger RNA in rheumatic patients, the present study aimed to assess the efficiency of the inactivated whole virus vaccines and viral vector COVID-19 vaccines in rheumatic diseases in Mashhad, Iran. Methods: This prospective cross-sectional study was conducted on ARDs patients who were referred to private clinics and rheumatologic clinics of Ghaem and Imam Reza Hospitals, Mashhad, Iran, during 2021-22. Anti-neutralizing antibodies have been considered to check antibodies of Sinopharm and Barkat vaccines, and an anti-spike antibody was considered to check Sputnik V and AstraZeneca vaccine antibodies. Humoral immunity was investigated using the anti-spike Enzyme-linked immunosorbent assay and anti-neutralizing antibodies. Results: The obtained results showed that humoral immunity after COVID-19 vaccination was observed in 73.9% of the patients with ARDs. However, humoral immunity was lower in ARDs patients who took tacrolimus and higher in patients with a history of COVID-19 infection (χ2=5.84, p=0.01). The infection after the second COVID-19 vaccination was lower in patients with humoral immunity (χ2=5.69, p=0.01). Conclusion: This study demonstrated that a homologous second dose of an inactivated whole viral vector SARS-CoV-2 vaccine was safe and provided a remarkable antibody response in ARDs patients.

Provider Guidance for the Prevention of Respiratory Syncytial Virus in Infants: Maternal Vaccination Versus Infant Monoclonal Antibody Treatment.

In 2023, the Food and Drug Administration approved 2 new products to reduce the risk of lower respiratory infections caused by respiratory syncytial virus (RSV) in infants: Beyfortus (nirsevimab; AstraZeneca/Sanofi), a single-dose monoclonal antibody for infant administration, and Abrysvo (bivalent RSVpreF vaccine; Pfizer), a single-dose maternal vaccination. We aimed to synthesize data from the literature and the leading professional organizations to provide guidance on RSV and strategies to reduce the risk of infant infection. This information will assist prenatal care clinicians in counseling their patients regarding the choice between maternal vaccination and the infant monoclonal antibody. A descriptive review of the guidelines from the Centers for Disease Control and Prevention, American College of Obstetrics and Gynecology (ACOG), American Academy of Pediatrics, Society for Maternal-Fetal Medicine, and the American Academy of Family Physicians. All 5 organizations recommend that RSV vaccination should be offered to all pregnant people during the RSV season (September-January in the continental United States). Infants younger than 8 months entering into their first RSV season born to those who did not receive maternal vaccination or received vaccination less than 14 days prior to birth should be offered monoclonal antibody administration. RSV vaccination and monoclonal antibodies have the potential to significantly reduce the burden of lower respiratory tract infections due to RSV in infants. Future studies should further evaluate the durability of protection and other strategies to further protect the infant, including cocooning and the role of breast milk in immunity.

Methotrexate treatment hampers induction of vaccine-specific CD4 T cell responses in patients with IMID

ObjectivesMethotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises...

The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial

The RTS,S/AS01E malaria vaccine showed lower antibody response and protective efficacy in infants aged 6-12 weeks compared with children aged 5-17 months (for whom this vaccine is recommended). We aimed to study the effect of previous Plasmodium falciparum exposure on the antibody responses to RTS,S/AS01E vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies. In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/AS01E phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous P falciparum exposure, which were later applied to RTS,S/AS01E-vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 P falciparum antigens using partial proteome microarrays. We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01E-vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior P falciparum exposure does not significantly affect antibody immunogenicity in children (Pearson's r=-0·02 [95% CI -0·13 to 0·10]). By contrast, high P falciparum exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6-12 months of life, correlated with reduced RTS,S/AS01E responses (r=-0·17 [-0·27 to -0·06]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage P falciparum antigens (r=-0·42 [-0·50 to -0·33]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=-0·44 [-0·55 to -0·33]), and involved antibodies to the central NANP region (r=-0·39 [-0·49 to -0·28]) but not the C-terminal region (r=0·02 [-0·10 to 0·15]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables. Interference between passive immunity and vaccine response is clinically significant and might affect the implementation of next-generation CSP-based vaccines for young infants and mothers as well as passive immunisation with human monoclonal antibodies. US National Institutes of Health, National Institute of Allergy and Infectious Diseases; PATH-Malaria Vaccine Initiative; Spanish Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), European Regional Development Fund and European Social Fund; Fundación Ramón Areces; Spanish Ministry of Science and Innovation; and Generalitat de Catalunya (CERCA Program).

Hepatitis a vaccine immunogenicity and boostability in adults receiving immunosuppressive therapy and adults living with HIV: a prospective single-Centre cohort study.

Hepatitis A (hepA) vaccination is highly immunogenic in healthy individuals, however there is uncertainty about the immunogenicity in immunocompromised populations (ICPs). In this prospective cohort study, people living with HIV (PLWH), patients on immunosuppressive mono- and combination therapy, and controls received two hepA vaccine doses at months 0 and 6-12, or three combined hepA/B vaccine doses at months 0, 1 and 6-12. Antibody levels were measured before and at different time-points post-vaccination (T2, 6, 8, 12months). The primary endpoint was the seroconversion rate (SCR) at T8, defined as hepA antibodies ≥20 mIU/ml. To assess boostability, an additional vaccine dose was administered 1-5years after T12 in those with antibodies < 50 mIU/ml, with antibody measurements before and seven days after the booster dose. We included 150 participants. At T2 SCRs ranged between 35-58% in ICPs versus 94% in controls. Among PLWH, patients on monotherapy, combination therapy and controls SCRs at T8 were 33/34 (97%), 32/34 (94%), 25/30 (83%) and 28/28 (100%) respectively. The booster dose resulted in 71% additional seroconversion (17/24), with only patients using combination therapy not responding. HepA vaccination is highly immunogenic in virologically suppressed PLWH and patients on immunosuppressive monotherapy, with SCRs after the complete hepA vaccination schedule similar to controls and adequate booster responses in case of waning immunity. However, patients using immunosuppressive combination therapy as well as all ICPs who did not receive the complete hepA vaccination schedule, are at risk of non-response to vaccination and post-vaccination antibody measurements are recommended.

Putting computational models of immunity to the test - an invited challenge to predict B. pertussis vaccination outcomes.

Systems vaccinology studies have been used to build computational models that predict individual vaccine responses and identify the factors contributing to differences in outcome. Comparing such models is challenging due to variability in study designs. To address this, we established a community resource to compare models predicting B. pertussis booster responses and generate experimental data for the explicit purpose of model evaluation. We here describe our second computational prediction challenge using this resource, where we benchmarked 49 algorithms from 53 scientists. We found that the most successful models stood out in their handling of nonlinearities, reducing large feature sets to representative subsets, and advanced data preprocessing. In contrast, we found that models adopted from literature that were developed to predict vaccine antibody responses in other settings performed poorly, reinforcing the need for purpose-built models. Overall, this demonstrates the value of purpose-generated datasets for rigorous and open model evaluations to identify features that improve the reliability and applicability of computational models in vaccine response prediction.

S03-02 PFAS exposure, vaccine antibody concentrations, and risk of infection among West African infants

S03-02 PFAS exposure, vaccine antibody concentrations, and risk of infection among West African infants

Protection of Omicron Bivalent Vaccine, Previous Infection, and Their Induced Neutralizing Antibodies Against Symptomatic Infection With Omicron XBB.1.16 and EG.5.1.

Data are limited on the protective role of the Omicron BA bivalent vaccine, previous infection, and their induced neutralizing antibodies against Omicron XBB.1.16 and EG.5.1 infection. We conducted a nested case-control analysis among tertiary hospital staff in Tokyo who had received ≥3 doses of COVID-19 vaccines and donated blood samples in June 2023 (1 month before the Omicron XBB.1.16 and EG.5.1 wave). We identified 206 symptomatic cases between June and September 2023 and selected their controls with 1:1 propensity score matching. We examined the association of vaccination, previous infection, and preinfection live virus neutralizing antibody titers against Omicron XBB.1.16 and EG.5.1 with the risk of COVID-19 infection. Previous infection during the Omicron BA- or XBB-dominant phase was associated with a significantly lower infection risk during the XBB.1.16 and EG.5.1-dominant phase than infection-naive status, with 70% and 100% protection, respectively, whereas Omicron BA bivalent vaccination showed no association. Preinfection neutralizing titers against XBB.1.16 and EG.5.1 were 39% (95% CI, 8%-60%) and 28% (95% CI, 8%-44%) lower in cases than matched controls. Neutralizing activity against XBB.1.16 and EG.5.1 was somewhat detectable in the sera of individuals with previous infection but barely detectable in those who were infection naive and received the Omicron bivalent vaccine. In the era when the Omicron XBB vaccine was unavailable, the Omicron BA bivalent vaccine did not confer the neutralizing activity and protection against Omicron XBB.1.16 and EG.5.1 symptomatic infection. The previous infection afforded neutralizing titers and protection against symptomatic infection with these variants.

Long-term postnatal exposure to air pollution and routine vaccine antibody levels in children

Long-term postnatal exposure to air pollution and routine vaccine antibody levels in children

Unveiling the Quest: Crafting an Enzyme-Linked Immunosorbent Assay (ELISA) Technique to Uncover COVID-19 Antibodies.

The COVID-19 pandemic, caused by the novel coronavirus SARS-CoV-2, has had a profound impact on global health. Rapid and accurate diagnostic tools are crucial for effective disease control and management. The enzyme-linked immunosorbent assay (ELISA) has emerged as a reliable and widely used method for detecting COVID-19 antibodies in patients, which develop in response to SARS-CoV-2 infection. While the ELISA technique is effective in identifying the presence of antibodies and thus confirming exposure to the virus, its role in predicting the clinical course and severity of the disease is limited. ELISA primarily confirms prior exposure to the virus or vaccination status, but it does not directly correlate antibody levels with the severity or progression of the disease. The variability in clinical outcomes is influenced by factors such as viral load, patient co-morbidities, genetic predispositions, and the timing of the immune response. ELISA has diverse applications in epidemiology, vaccination assessment, and therapeutic development. It determines antibody prevalence, aids in surveillance, and evaluates vaccine effectiveness and antibody protection duration. ELISA quantitatively measures antibody levels, providing insights into the immune response and treatment efficacy. Challenges include specialized facilities and personnel, cross-reactivity, and false results. Multiplex assays and integration with other diagnostics are future directions. In summary, ELISA is an essential tool in COVID-19 diagnostics, enabling precise assessment of the immune response and contributing to effective strategies. The development of point-of-care devices that integrate ELISA technology could enable rapid and accessible testing in various settings. Additionally, integrating ELISA with other diagnostic platforms could enhance the overall diagnostic capabilities for COVID-19. Despite challenges, ongoing advancements in ELISA technology, and its integration with other diagnostic approaches, hold promise for further improving COVID-19 diagnostics and management strategies.

Impact of glycan depletion, glycan debranching and increased glycan charge on HIV-1 neutralization sensitivity and immunogenicity.

Broadly neutralizing antibodies (bNAbs) isolated from HIV-1 infected donors are vaccine paradigms. These bNAbs recognize envelope glycoprotein trimers that carry 75-90 oligomannose and complex-type glycans. Although bNAbs and their precursors must navigate past glycans, they usually also make some glycan contacts. Glycan-modified vaccines may therefore be useful to initiate and guide bNAb development. Here, we describe two ways to modify Env glycans for possible vaccine use: 1) using a cocktail of glycosidases (termed "NGAF3" (Neuraminidase, β-Galactosidase, N-Acetylglucosaminidase, endoglycosidase F3 (endo F3)) to deplete complex glycans to try to minimize bNAb-glycan clashes and 2) co-expressing β-1,4-galactosyltransferase 1 (B4G) and β-galactoside α-2,6 sialyltransferase 1 (ST6) during Env biosynthesis, creating bNAb-preferred glycan structures. Mass spectrometry revealed that NGAF3 removed glycan heads at 3/7 sites occupied by complex glycans. B4G overexpression resulted in hybrid glycan development whenever complex glycans were closely spaced. The glycan at position 611 in of Env's gp41 transmembrane subunit was uniquely isolated from the effects of both endo F3 and B4G. B4G and ST6 co-expression increased hybrid and sialylated glycan abundance, reducing glycan complexity. In rabbit vaccinations, B4G+ST6 virus-like particles (VLPs) induced less frequent, weaker titer NAbs, implying that ST6-mediated increased Env charge dampens vaccine antibodies. In some cases, vaccine sera preferentially neutralized B4G+ST6-modified pseudovirus. HIV-1+ donor plasma NAbs were generally more effective against B4G+ST6 modified pseudovirus, suggesting a preference for less complex and/or α-2,6 sialylated Env trimers. Collectively, our data suggest that B4G and ST6 Env modifications are best suited for intermediate or late vaccine shots.

Anti-SARS-CoV-2 Antibodies versus Vaccination Status in CAD Patients with COVID-19: A Prospective, Propensity Score-Matched Cohort Study.

Despite the currently prevailing, milder Omicron variant, coronary artery disease (CAD) patients constitute a major risk group in COVID-19, exhibiting 2.6 times the mortality risk of non-CAD patients and representing over 22% of non-survivors. No data are currently available on the efficacy of antibody levels in CAD patients, nor on the relevance of vaccination status versus antibody levels for predicting severe courses and COVID-19 mortality. Nor are there definitive indicators to assess if individual CAD patients are sufficiently protected from adverse outcomes or to determine the necessity of booster vaccinations. A prospective, propensity-score-matched, multicenter cohort study comprising 249 CAD patients and 903 controls was conducted. Anti-SARS-CoV-2-spike antibodies were measured on hospital admission. Prespecified endpoints were in-hospital mortality, intensive care, and oxygen administration. After adjustment for potential confounders, CAD patients exhibited 4.6 and 6.1-times higher mortality risks if antibody levels were <1200 BAU/mL and <182 BAU/mL, respectively, compared to CAD patients above these thresholds (aOR 4.598, 95%CI 2.426-8.714, p < 0.001; 6.147, 95%CI 2.529-14.941, p < 0.001). Risk of intensive care was 3.7 and 4.0 (p = 0.003; p < 0.001), and risk of oxygen administration 2.6 and 2.4 times higher below these thresholds (p = 0.004; p = 0.010). Vaccination status was a weaker predictor of all three outcomes than both antibody thresholds. Antibody levels are a stronger predictor of outcome in CAD patients with COVID-19 than vaccination status, with 1200 BAU/mL being the more conservative threshold. Measuring anti-SARS-CoV-2 antibodies in CAD patients may ensure enhanced protection by providing timely booster vaccinations and identifying high-risk CAD patients at hospital admission.