Low Antibody Research Articles

Immunogenicity after COVID-19 vaccination in patients with solid tumor and hospital staff: A prospective single-center observational study.

10626 Background: Patients with tumor are at high risk of severe COVID-19, and vaccination against SARS-CoV-2 is recommended. Impact of cancer treatment on immunogenicity has not been evaluated well. Methods: This prospective study was conducted to assess the seroconversion rate of SARS-CoV-2 vaccines among patients with cancer and hospital staff. Further, we focused on the difference among cancer treatment regimens. SARS-CoV-2 spike protein-specific IgG (S-IgG) were evaluated before the first vaccination, 1–3 months, 4–6 months, and 7–12 months after the second vaccination, and 1–3 months after the third vaccination. The primary endpoint was seroconversion rate measured 1–3 months after the second vaccination. Results: From April 2021 to November 2021, consent was obtained from 629 cancer patients and 210 hospital staff. Excluding missing data and withdrawal of consent, 590 cancer patients and 183 hospital staff without complications was analyzed. At 1–3 months after the second vaccination, S-IgG antibody concentration higher than the cut-off value (20 BAU/mL) was found in 96.1% (567/590) patients with cancer and 100% (183/183) of the healthy controls (p = 0.0024). At 4–6 months after second vaccination, S-IgG antibody concentration higher than the cut-off value was found in 93.1% (461/495) patients with cancer and 100% (170/170) of the healthy controls (p < 0.0001). The significant difference in seroconversion rate between the two groups persisted even after 7-12 months. Patients undergoing treatment regimens such as platinum combination therapy (median: 423.7, 95% CI: 264.2–767.0, p = 0.003) and alkylating agent (median: 57.5, 95% CI: 5.4–748, p < 0.0001) among cytotoxic drugs, and PARP inhibitor (median: 264, 95% CI: 43–690.4, p = 0.0004), mTOR inhibitor (median: 227.4, 95% CI: 5.7–323.4, p = 0.0036), BCR-ABL inhibitor among drugs (median: 124.4, 95% CI: 0.0–288.9, p = 0.005) among target molecule drugs showed lower antibody titer compared to the no-treatment patients with cancer group. Conclusions: SARS-CoV-2 vaccine immunogenicity was low among patients with cancer compared to healthy control. Also, several treatment regimens were found to negatively impact immune response. Clinical trial information: UMIN000049403 , UMIN000049430 . [Table: see text]

Preparation and Biological Properties of Oligonucleotide-Functionalized Virus-like Particles.

Oligonucleotides are powerful molecules for programming function and assembly. When arrayed on nanoparticle scaffolds in high density, the resulting molecules, spherical nucleic acids (SNAs), become imbued with unique properties. We used the copper-catalyzed azide-alkyne cycloaddition to graft oligonucleotides on Qβ virus-like particles to see if such structures also gain SNA-like behavior. Copper-binding ligands were shown to promote the click reaction without degrading oligonucleotide substrates. Reactions were first optimized with a small-molecule fluorogenic reporter and were then applied to the more challenging synthesis of polyvalent protein nanoparticle-oligonucleotide conjugates. The resulting particles exhibited the enhanced cellular uptake and protection from nuclease-mediated oligonucleotide cleavage characteristic of SNAs, had similar residence time in the liver relative to unmodified particles, and were somewhat shielded from immune recognition, resulting in nearly 10-fold lower antibody titers relative to unmodified particles. Oligonucleotide-functionalized virus-like particles thus provide an interesting option for protein nanoparticle-mediated delivery of functional molecules.

Durability and determinants of anti-SARS-CoV-2 spike antibodies following the second and third doses of mRNA COVID-19 vaccine

ObjectivesTo examine the differences in durability and its determinants of humoral immunity following 2- and 3-dose COVID-19 vaccination. MethodsThroughout the pandemic, we evaluated the anti-spike IgG antibody titers of 2- and 3-dose mRNA vaccine recipients over time among the staff of a medical and research center in Tokyo. Linear mixed models were used to estimate trajectories of antibody titers from 14 to 180 days after the last immune-conferred event (vaccination or infection) and compare antibody waning rates across prior infection and vaccination status, and across background factors in infection-naïve participants. ResultsA total of 6901 measurements from 2964 participants (median age, 35 years; 30% male) were analyzed. Antibody waning rate (percentage per 30 days [95% CI]) was slower after 3 doses (25% [23–26]) than 2 doses (36% [35–37]). Participants with hybrid immunity (vaccination and infection) had further slower waning rates: 2-dose plus infection (16% [9–22]); 3-dose plus infection (21% [17–25]). Older age, male sex, obesity, coexisting diseases, immunosuppressant use, smoking, and alcohol drinking were associated with lower antibody titers, whereas these associations disappeared after 3 doses, except for sex (lower in female participants) and immunosuppressant use. Antibody waned slightly faster in older participants, females, and alcohol drinkers after 2 doses, whereas it did not differ after 3 doses across except sex. DiscussionThe 3-dose mRNA vaccine conferred higher durable antibody titers, and previous infection modestly enhanced its durability. The antibody levels at a given time point and waning speed after 2 doses differed across background factors; however, these differences mostly diminished after 3 doses.

Host-genetic-based outcome of co-infection by PCV2b and PRRSV in pigs.

Replication of porcine circovirus type 2 (PCV2), an important worldwide swine pathogen, has been demonstrated to be influenced by host genotype. Specifically, a missense DNA polymorphism (SYNGR2 p.Arg63Cys) within the SYNGR2 gene was demonstrated to contribute to variation in PCV2b viral load and subsequent immune response following infection. PCV2 is known to induce immunosuppression leading to an increase in susceptibility to subsequent infections with other viral pathogens such as porcine reproductive and respiratory syndrome virus (PRRSV). In order to assess the role of SYNGR2 p.Arg63Cys in co-infections, pigs homozygous for the favorable SYNGR2 p.63Cys (N = 30) and unfavorable SYNGR2 p.63Arg (N = 29) alleles were infected with PCV2b followed a week later by a challenge with PRRSV. A lower PCV2b viremia (P < 0.001) and PCV2-specific IgM antibodies (P < 0.005) were observed in SYNGR2 p.63Cys compared to SYNGR2 p.63Arg genotypes. No significant differences in PRRSV viremia and specific IgG antibodies were observed between SYNGR2 genotypes. Lung histology score, an indicator of disease severity, was lower in the pigs with SYNGR2 p.63Cys genotypes (P < 0.05). Variation in the lung histology scores within SYNGR2 genotypes suggests that additional factors, environmental and/or genetic, could be involved in disease severity.

Antibody response and safety of inactivated SARS-CoV-2 vaccines in chronic hepatitis B patients with and without cirrhosis.

The immune response and safety of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines among patients with chronic hepatitis B (CHB), especially those with cirrhosis, are not clear. Therefore, this study was conducted to evaluate the efficacy and safety of inactivated SARS-CoV-2 vaccines among CHB patients with and without cirrhosis. A total of 643 CHB patients who received two doses of inactivated SARS-CoV-2 vaccines (BBIBP-CorV and CoronaVac) were enrolled. Serum samples were collected and tested for SARS-CoV-2 S-receptor-binding domain (S-RBD) immunoglobulin G (IgG) at enrollment. Data on adverse events (AEs) within 7days after the second dose were obtained using a questionnaire. A total of 416 non-cirrhotic and 227 cirrhotic patients were included in the analysis. Cirrhotic patients had lower antibody titers than non-cirrhotic patients after adjusting for age, sex, and time interval (2.45 vs. 2.60ng/ml, p=0.034). Furthermore, the study revealed that cirrhotic patients demonstrated a slower rate of seropositivity increase, with the highest rate being recorded at week4 and reaching 94.7%. On the other hand, among non-cirrhotic patients, the seropositivity rate peak was observed at week2 and reached 96.0%. In addition, cirrhotic patients displayed a more rapid decline in the seropositivity rate, dropping to 54.5% after ≥16weeks, while non-cirrhotic patients exhibited a decrease to 67.2% after the same time period. The overall incidence of AEs was low (18.4%), and all AEs were mild and self-limiting. In addition, 16.0% of participants had mild liver function abnormalities, and half of them returned to normality within the next 6months without additional therapy. The participants who experienced liver function abnormalities showed a higher seropositivity rate and antibody titer than those who did not (91.6% vs. 79.5%, p=0.005; 2.73 vs. 2.41ng/ml, p<0.001). Cirrhotic CHB patients had lower antibody titers to inactivated SARS-CoV-2 vaccines than non-cirrhotic patients. The vaccines were generally well tolerated in both non-cirrhotic and cirrhotic CHB patient groups. Patients with abnormal liver function may have a better antibody response than those without.

Analysis and comparison of SARS-CoV-2 variant antibodies and neutralizing activity for 6 months after a booster mRNA vaccine in a healthcare worker population.

In the context of recurrent surges of SARS-CoV-2 infections, a detailed characterization of antibody persistence over a 6-month period following vaccine booster dose is necessary to crafting effective public health policies on repeat vaccination. To characterize the SARS-CoV-2 antibody profile of a healthcare worker population over a 6-month period following mRNA vaccination and booster dose. 323 healthcare workers at an academic medical center in Orange County, California who had completed primary vaccination and booster dose against SARS-CoV-2 were recruited for the study. A total of 690 blood specimens over a 6-month period were collected via finger-stick blood and analyzed for the presence of antibodies against 9 SARS-CoV-2 antigens using a coronavirus antigen microarray. The primary outcome of this study was the average SARS-CoV-2 antibody level as measured using a novel coronavirus antigen microarray. Additional outcomes measured include levels of antibodies specific to SARS-CoV-2 variants including Delta, Omicron BA.1, and BA.2. We also measured SARS-CoV-2 neutralization capacity for a subset of the population to confirm correlation with antibody levels. Although antibodies against SARS-CoV-2 wane throughout the 6-month period following a booster dose, antibody levels remain higher than pre-boost levels. However, a booster dose of vaccine based on the original Wuhan strain generates approximately 3-fold lower antibody reactivity against Omicron variants BA.1 and BA.2 as compared to the vaccine strain. Despite waning antibody levels, neutralization activity against the vaccine strain is maintained throughout the 6-month period. In the context of recurrent surges of SARS-CoV-2 infections, our data indicate that breakthrough infections are likely driven by novel variants with different antibody specificity and not by time since last dose of vaccination, indicating that development of vaccinations specific to these novel variants is necessary to prevent future surges of SARS-CoV-2 infections.

Psychosocial and behavioural predictors of immune response to influenza vaccination: a systematic review and meta-analysis

ABSTRACT High variability of influenza vaccine efficacy requires the identification of modulators of immunisation that may be targeted as adjuvants in health psychology interventions. Psychosocial and behavioural variables such as psychological stress, greater negative and lower positive affectivity, poor sleep, loneliness, and lack of social support, have been associated with abnormal immune and inflammatory responses and negative health outcomes, yet their effects in modulating vaccine efficacy are yet to be fully understood. We conducted an updated systematic review of longitudinal and experimental studies examining the effects of such variables in predicting immune response to influenza vaccine. PubMed, Medline, PsycINFO, CINAHL and Scopus were searched up to November 2022. Twenty-five studies met the inclusion criteria for qualitative synthesis and 16 provided data for meta-analysis. Low positive and high negative affect were associated with low antibodies and weak cell-mediated immunity following vaccination in qualitative synthesis. Literature on sleep disturbance, loneliness and social support was limited and yielded inconsistent results. Psychological stress was associated with poorer antibody response in meta-analysis. In conclusion, findings from this review suggest a need for further longitudinal and experimental studies on these factors to support their inclusion as target variables in vaccine adjuvant interventions.

P54 ORAL ANTIVIRALS RITONAVIR-NIRMATRELVIR AND MOLNUPIRAVIR ARE HIGHLY EFFECTIVE IN PATIENTS WITH MULTIPLE MYELOMA AND COVID-19; A SINGLE-CENTER, PROSPECTIVE STUDY

P54 ORAL ANTIVIRALS RITONAVIR-NIRMATRELVIR AND MOLNUPIRAVIR ARE HIGHLY EFFECTIVE IN PATIENTS WITH MULTIPLE MYELOMA AND COVID-19; A SINGLE-CENTER, PROSPECTIVE STUDY

The immune response of SARS-CoV-2 vaccine in population with obesity: a systematic review

Link of Video Abstract: https://youtu.be/rXb-E8We3vU Background: COVID-19 vaccines involve a humoral response to produce a neutralizing antibody that could protect subjects from severe COVID-19 infection. However, obesity tends to lower the immune response to the COVID-19 vaccine. Therefore, we conducted a systematic review to determine the immune response of various types of COVID-19 vaccines in a population with obesity. Methods: We conducted a systematic review based on The Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. Using keywords, we search studies from Taylor &amp; Francis, PubMed, ScienceDirect, Cochrane, and EBSCOHost. Results: We included eight cohort studies with 21,280 subjects after thorough selection and appraisal. Four studies stated that obesity was related to lower antibody titer post-SARS-CoV-2 vaccination, even though one study stated that obesity was not associated with long-term immune response. Another prospective cohort study involving approximately nine million populations stated that SARS-CoV-2 vaccination provided similar protection against COVID-19 compared to normoweight when underweight was a risk factor for lower protection. One study found that antibody titer wanes faster in obesity compared to normoweight. In addition, another study found lower antibody titer in obese men, whereas no significant findings were found in obese women. Conclusion: Therefore, it should be noted that COVID-19 vaccination in an obese population tends to provide a lower immune response regardless of vaccine type and doses are given. This should inform clinicians who want to administer the COVID-19 vaccine to obese populations.

Anti-tumor necrosis factor therapy is associated with attenuated humoral response to SARS-COV-2 vaccines in patients with inflammatory bowel disease

BackgroundImmunosuppressive therapy used in the treatment of inflammatory bowel disease (IBD) is known to reduce vaccine immunogenicity. AimsThis study aimed to 1) predict the humoral response elicited by SARS-CoV-2 vaccination in IBD patients based on their ongoing treatment and other relevant patient and vaccine characteristics and 2) assess the humoral response to a booster dose of mRNA vaccine. MethodsWe conducted a prospective study in adult IBD patients. Anti-spike (S) IgG antibodies were measured after initial vaccination and again after one booster dose. A multiple linear regression model was created to predict anti-S antibody titer following initial complete vaccination in different therapeutic groups (no immunosuppression, anti-TNF, immunomodulators and combination therapy). A two-tailed Wilcoxon test for two dependent groups was performed to compare anti-S values before and after the booster dose. ResultsOur study included 198 IBD patients. The multiple linear regression identified anti-TNF and combination therapy (versus no immunosuppression), current smoking, viral vector (versus mRNA) vaccine and interval between vaccination and anti-S measurement as statistically significant predictors of the log anti-S antibody levels (p < 0.001). No statistically significant differences were found between no immunosuppression and immunomodulators (p = 0.349) and between anti-TNF and combination therapy (p = 0.997). Statistically significant differences for anti-S antibody titer before and after the booster dose of mRNA SARS-CoV-2 vaccine were found, both for non-anti-TNF and anti-TNF groups. ConclusionsAnti-TNF treatment (either alone or in combination therapy) is associated with lower anti-S antibody levels. Booster mRNA doses seem to increase anti-S both in non-anti-TNF and anti-TNF treated patients. Special attention should be paid to this group of patients when planning vaccination schemes.

Effects of diabetes mellitus regulation on antibody response to inactivated virus vaccine: a systematic review

Background: Diabetes mellitus (DM) could hamper the immune responses, including that induced by the vaccine. The aim of this study was to evaluate the immunogenicity of coronavirus disease 2019 (COVID-19-19) inactivated vaccines in patients with DM either controlled or uncontrolled through a systematic review approach. Methods: Without regard to time constraints, searches were conducted in ProQuest, Embase, and PubMed to assess the available data on the impact of DM regulation on the immunogenicity of post-vaccinated DM patients. The PRISMA guideline and the PICO criteria were used. The quality of studies was assessed using the National Institutes of Health (NIH) quality assessment tool. There is not enough Available data comparing the immunogenicity of the vaccine in controlled and uncontrolled DM patients is limited. Results: Out of 20,657 articles, five studies were included, of which three had good quality and two had fair quality. Our data suggested that DM patients vaccinated with CoronaVac/SinoVac had lower seroconversion rates significantly lower compared to non-DM patients. The immunogenicity of BBV-152 vaccine in DM patients was also significantly lower than in patients without DM. Studies comparing the immunogenicity of the vaccine between controlled and uncontrolled DM patients are limited. Conclusion: Patients with DM have lower antibody levels than non-DM patients who received inactivated COVID-19 patients. Glycemic management has emerged as critical to maximizing the immunogenicity induced by inactivated vaccines in a small number of patients; however, to support this conclusion, studies with adequate number of patients are critical.

Post-discharge health assessment in survivors of coronavirus disease: a time-point analysis of a prospective cohort study.

The objective of this study was to quantitatively evaluate psychological and quality of life-related complications at three months following discharge in hospitalized coronavirus disease 2019 (COVID-19) patients during the pandemic in Iran. In this time-point analysis of prospective cohort study data, adult patients hospitalized with symptoms suggestive of COVID-19 were enrolled. Patients were stratified in analyses based on severity. The primary outcomes consisted of psychological problems and pulmonary function tests (PFTs) in the three months following discharge, with Health-related quality of life (HRQoL) as the secondary outcome. Exploratory predictors were determined for both primary and secondary outcomes. 283 out of 900 (30%) eligible patients were accessible for the follow-up assessment and included in the study. The mean age was 53.65 ± 13.43years, with 68% experiencing a severe disease course. At the time of the final follow-up, participants still reported persistent symptoms, among which fatigue, shortness of breath, and cough were the most common. Based on the regression-adjusted analysis, lower levels of forced expiratory volume in one second (FEV1) to forced vital capacity (FVC) ratio was associated with higher levels of depression (standardized β = -0.161 (SE = 0.042), P = 0.017) and stress levels (standardized β =-0.110 (SE = 0.047), P = 0.015). Furthermore, higher levels of anti-SARS-CoV-2 immunoglobulin-M (IgM) were associated with significantly lower levels of depression (standardized β = -0.139 (SE = 0.135), P = 0.031). There is an association between lung damage during COVID-19 and the reduction of pulmonary function for up to three months from acute infection in hospitalized patients. Varying degrees of anxiety, depression, stress, and low HRQoL frequently occur in patients with COVID-19. More severe lung damage and lower COVID-19 antibodies were associated with lower levels of psychological health.

Pre-existing immunity modulates responses to mRNA boosters

Abstract mRNA vaccines have shown high efficacy in preventing severe COVID-19, but breakthrough infections, emerging variants and waning antibody levels have warranted the use of boosters. Although mRNA boosters have been widely implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT162b2 vaccines, we observed that lower spike-specific antibody levels before boost were associated with higher fold-increase in spike-specific antibody levels after boost, suggesting that pre-existing antibodies to SARS-CoV-2 downmodulate the immunogenicity of mRNA-based vaccines. Similar effects were observed in mice that received mRNA-based SARS-CoV-2 vaccines and HIV-1 vaccines. Our subsequent studies in mice show that pre-existing antibodies against the antigen encoded by the mRNA vaccine itself accelerate the clearance of vaccine antigen following a booster vaccination, via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses. These data suggest that transient downmodulation of antibody effector functions may improve the efficacy of mRNA boosters against SARS-CoV-2 and other diseases. Start-up chart string, Northwestern University National Institute on Drug Abuse (NIDA, DP2DA051912)

Determinants of humoral and cellular immune responses to three doses of mRNA SARS-CoV-2 vaccines in older adults: a longitudinal cohort study

Older age is associated with poorer outcomes to COVID-19 infection. The Norwegian Institute of Public Health established a longitudinal cohort of adults aged 65-80 years to study the effects of the COVID-19 pandemic. Here we describe the characteristics of the cohort in general, and specifically the immune responses at baseline and after primary and booster vaccination in a subset of longitudinal blood samples, and the epidemiological factors affecting these responses. 4551 participants were recruited, with humoral (n=299) and cellular (n=90) responses measured before vaccination and after two and three vaccine doses. Information on general health, infections, and vaccinations were obtained from questionnaires and national health registries. Half of the participants had a chronic condition. 849 (18·7%) of 4551 were prefrail and 184 (4%) of 4551 were frail. 483 (10·6%) of 4551 had general activity limitations (scored with the Global Activity Limitation Index). After dose two, 295 (98·7%) of 299 participants were seropositive for anti-receptor binding domain IgG, and 210 (100%) of 210 participants after dose three. Spike-specific CD4 and CD8 T cell responses showed high heterogeneity after vaccination and responded to the alpha (B.1.1.7), delta (B.1.617.2), and omicron (B.1.1.529 or BA.1) variants of concern. Cellular responses to seasonal coronaviruses increased after SARS-CoV-2 vaccination. Heterologous prime boosting with mRNA vaccines was associated with the highest antibody (p=0·019) and CD4 T cell responses (p=0·003), and hypertension with lower antibody levels after three doses (p=0·04). Most older adults, including those with comorbidities, generated good serological and cellular responses after two vaccine doses. Responses further improved after three doses, particularly after heterologous boosting. Vaccination also generated cross-reactive T cells against variants of concern and seasonal coronaviruses. Frailty was not associated with impaired immune responses, but hypertension might indicate reduced responsiveness to vaccines even after three doses. Individual differences identified through longitudinal sampling enables better prediction of the variability of vaccine responses, which can help guide future policy on the need for subsequent doses and their timing. Norwegian Institute of Public Health, Norwegian Ministry of Health, Research Council of Norway, and Coalition for Epidemic Preparedness Innovations.

Altered antibody profiles after receipt of third dose SARS-CoV-2 mRNA vaccines in solid organ transplant recipients

Abstract Immunosuppressed patients, including solid organ transplant recipients (SOTRs), developed significantly lower antibody responses and had more breakthrough infections after two doses of COVID-19 mRNA vaccines, as compared with immunocompetent individuals. The aim of this study was to characterize vaccine-induced antibody responses, including IgG binding antibodies and live virus neutralizing antibodies (NAb) against the vaccine strain and Omicron variants, BA.1 and BA.5, as well as the levels of the IgG subclasses, IgG1-4, in SOTRs. Serum samples from SOTRs were analyzed at pre-vaccination, 30-days, and 90-days following the third dose COVID-19 mRNA vaccines (D3). For several measures, antibody responses were compared with healthy controls (HC). A third dose vaccination increased anti-spike (S) IgG titers in response to the SARS-CoV-2 vaccine and Omicron variants from pre- to post-D3 in SOTRs. Anti-S IgG responses to Omicron variants, however, were significantly lower than to the vaccine strain. SOTRs also had low live virus NAb titers to the vaccine and Omicron BA.1 variant, with many individuals having no detectable NAb. The subclass-specific anti-S IgG antibodies against the SARS-CoV-2 vaccine strain predominantly consisted of IgG1, IgG3, and IgG4 in SOTRs, which resembled the subclass profiles in HC at post-D3. Together, our findings illustrate that while a booster dose of mRNA vaccine induces antibody responses, including IgG1 and IgG3, which are the dominant antiviral IgG subclasses, in SOTRs, these responses are still lower than immunocompetent individuals. Therefore, consideration should be given to different formulations and doses of COVID-19 vaccines in people with severely compromised immune systems.

NEI supplementation improves alum-based immunity in CFTR KO mice

Abstract Cystic fibrosis (CF) is a genetic disorder that causes severe damage to the lungs and digestive system. CF affects the cells that produce mucus, sweat, and digestive enzymes and is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Expression and function of CFTR have been extensively studied on epithelial cells and several recent publications have shown that CFTR also regulates the functions of myeloid cells. We addressed whether CFTR is expressed by B cells and the role of CFTR in B cell functions. We found that CFTR is expressed on murine and human B cells. Compared to control wild-type (WT) mice, CFTR KO exhibited reduced frequency of B cells in lymphoid tissues and lower levels of serum immunoglobulin isotypes. Upon systemic immunization with an alum-based vaccine, CFTR KO mice developed lower antibody responses than control mice. Interestingly, vaccine supplementation with an inhibitor of the serine protease elastase (NEI) enhanced the titers of vaccine-specific serum antibody responses in CFTR KO mice and CFTR heterozygote (CFTR Het) mice. We have previously reported that NEI supplementation could promote mucosal immunity in mice immunized with the alum-based injected vaccine. In this regard, CFTR KO and CFTR Het mice immunized with NEI-supplemented alum-based injected developed higher IgA and IgG responses in saliva than control WT mice. These results provide new insights on the regulatory role of CFTR for B cell differentiation and function. They also suggest that vaccine supplementation with NEI could improve protection of individuals leaving with CF against respiratory pathogens. NIH R01 DK101323

Sex differences in the efficacy and safety of SARS-CoV-2 vaccination in residents of long-term care facilities: insights from the GeroCovid Vax study

Despite the reported sex-related variations in the immune response to vaccination, whether the effects of SARS-CoV-2 vaccination differ by sex is still under debate, especially considering old vulnerable individuals, such as long-term care facilities (LTCFs) residents. This study aimed to evaluate COVID-19 infections, adverse events, and humoral response after vaccination in a sample of LTCF residents. A total of 3259 LTCF residents (71% females; mean age: 83.4 ± 9.2 years) were enrolled in the Italian-based multicenter GeroCovid Vax study. We recorded the adverse effects occurring during the 7 days after vaccine doses and COVID-19 cases over 12 months post-vaccination. In a subsample of 524 residents (69% females), pre- and post-vaccination SARS-CoV-2 trimeric S immunoglobulin G (Anti-S-IgG) were measured through chemiluminescent assays at different time points. Only 12.1% of vaccinated residents got COVID-19 during the follow-up, without any sex differences. Female residents were more likely to have local adverse effects after the first dose (13.3% vs. 10.2%, p = 0.018). No other sex differences in systemic adverse effects and for the following doses were recorded, as well as in anti-S-IgG titer over time. Among the factors modifying the 12-month anti-S-IgG titers, mobility limitations and depressive disorder were more likely to be associated with higher and lower levels in the antibody response, respectively; a significantly lower antibody titer was observed in males with cardiovascular diseases and in females with diabetes or cognitive disorders. The study suggests that, among LTCF residents, SARS-CoV-2 vaccination was effective regardless of sex, yet sex-specific comorbidities influenced the antibody response. Local adverse reactions were more common in females.

SARS-CoV-2 Serology Across Scales: A Framework for Unbiased Estimation of Cumulative Incidence Incorporating Antibody Kinetics and Epidemic Recency.

Serosurveys are a key resource for measuring severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) population exposure. A growing body of evidence suggests that asymptomatic and mild infections (together making up over 95% of all infections) are associated with lower antibody titers than severe infections. Antibody levels also peak a few weeks after infection and decay gradually. We developed a statistical approach to produce estimates of cumulative incidence from raw seroprevalence survey results that account for these sources of spectrum bias. We incorporate data on antibody responses on multiple assays from a postinfection longitudinal cohort, along with epidemic time series to account for the timing of a serosurvey relative to how recently individuals may have been infected. We applied this method to produce estimates of cumulative incidence from 5 large-scale SARS-CoV-2 serosurveys across different settings and study designs. We identified substantial differences between raw seroprevalence and cumulative incidence of over 2-fold in the results of some surveys, and we provide a tool for practitioners to generate cumulative incidence estimates with preset or custom parameter values. While unprecedented efforts have been launched to generate SARS-CoV-2 seroprevalence estimates over this past year, interpretation of results from these studies requires properly accounting for both population-level epidemiologic context and individual-level immune dynamics.

Storage time and temperature of filter paper strips affect anti-West Nile virus antibody detection in 2 galliform species.

The effects of filter paper strip (FPS) storage time and temperature on antibody detection are poorly understood despite widespread use in wildlife research. We collected sera and FPSs from 23 wild turkeys (Meleagris gallopavo) and 20 northern bobwhites (Colinus virginianus) experimentally infected with West Nile virus (WNV) to compare FPS storage methods with WNV plaque reduction neutralization test (PRNT) sensitivity. FPS storage methods included: immediate elution after drying, and storage at -20°C for 3 mo, -20°C for 6 mo, room temperature (RT) for 3 mo, and RT for 6 mo prior to elution. FPS eluates and sera were co-titrated to determine endpoint antibody titers, which were compared between FPS sera eluted immediately and sera, and among FPS eluates that underwent different storage conditions. Antibody titers were ~4-fold less in FPS sera eluted immediately versus sera, and dropped more frequently below PRNT detection threshold in northern bobwhites, which had ~10-fold lower serum antibody titers than wild turkeys. Antibody titers were lower in FPS samples stored at RT and for 6 mo. WNV serologic surveys may result in falsely low seroprevalence estimates if FPSs are stored at RT for ≥ 3 mo before elution.

Obesity Is Associated with an Impaired Baseline Repertoire of Anti-Influenza Virus Antibodies.

Obesity is a risk factor for severe disease and mortality for both influenza and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. While previous studies show that individuals with obesity generate antibody responses following influenza vaccination, infection rates within the obese group were twice as high as those in the healthy-weight group. The repertoire of antibodies raised against influenza viruses following previous vaccinations and/or natural exposures is referred to here as baseline immune history (BIH). To investigate the hypothesis that obesity impacts immune memory to infections and vaccines, we profiled the BIH of obese and healthy-weight adults vaccinated with the 2010-2011 seasonal influenza vaccine in response to conformational and linear antigens. Despite the extensive heterogeneity of the BIH profiles in both groups, there were striking differences between obese and healthy subjects, especially with regard to A/H1N1 strains and the 2009 pandemic virus (Cal09). Individuals with obesity had lower IgG and IgA magnitude and breadth for a panel of A/H1N1 whole viruses and hemagglutinin proteins from 1933 to 2009 but increased IgG magnitude and breadth for linear peptides from the Cal09 H1 and N1 proteins. Age was also associated with A/H1N1 BIH, with young individuals with obesity being more likely to have reduced A/H1N1 BIH. We found that individuals with low IgG BIH had significantly lower neutralizing antibody titers than individuals with high IgG BIH. Taken together, our findings suggest that increased susceptibility of obese participants to influenza infection may be mediated in part by obesity-associated differences in the memory B-cell repertoire, which cannot be ameliorated by current seasonal vaccination regimens. Overall, these data have vital implications for the next generation of influenza virus and SARS-CoV-2 vaccines. IMPORTANCE Obesity is associated with increased morbidity and mortality from influenza and SARS-CoV-2 infection. While vaccination is the most effective strategy for preventing influenza virus infection, our previous studies showed that influenza vaccines fail to provide optimal protection in obese individuals despite reaching canonical correlates of protection. Here, we show that obesity may impair immune history in humans and cannot be overcome by seasonal vaccination, especially in younger individuals with decreased lifetime exposure to infections and seasonal vaccines. Low baseline immune history is associated with decreased protective antibody responses. Obesity potentially handicaps overall responses to vaccination, biasing it toward responses to linear epitopes, which may reduce protective capacity. Taken together, our data suggest that young obese individuals are at an increased risk of reduced protection by vaccination, likely due to altered immune history biased toward nonprotective antibody responses. Given the worldwide obesity epidemic coupled with seasonal respiratory virus infections and the inevitable next pandemic, it is imperative that we understand and improve vaccine efficacy in this high-risk population. The design, development, and usage of vaccines for and in obese individuals may need critical evaluation, and immune history should be considered an alternate correlate of protection in future vaccine clinical trials.