Persistent SARS-CoV-2-specific immune defects in kidney transplant recipients following third mRNA vaccine dose.

Kidney transplant recipients (KTRs) show poorer response to SARS-CoV-2 mRNA vaccination, yet response patterns and mechanistic drivers following third doses are ill-defined. We administered third monovalent mRNA vaccines to n = 81 KTRs with negative or low-titer anti-receptor binding domain (RBD) antibody (n = 39 anti-RBDNEG; n = 42 anti-RBDLO), compared with healthy controls (HCs, n = 19), measuring anti-RBD, Omicron neutralization, spike-specific CD8+%, and SARS-CoV-2-reactive T cell receptor (TCR) repertoires. By day 30, 44% anti-RBDNEG remained seronegative; 5% KTRs developed BA.5 neutralization (vs 68% HCs, P < .001). Day 30 spike-specific CD8+% was negative in 91% KTRs (vs 20% HCs; P = .07), without correlation to anti-RBD (rs = 0.17). Day 30 SARS-CoV-2-reactive TCR repertoires were detected in 52% KTRs vs 74% HCs (P = .11). Spike-specific CD4+ TCR expansion was similar between KTRs and HCs, yet KTR CD8+ TCR depth was 7.6-fold lower (P = .001). Global negative response was seen in 7% KTRs, associated with high-dose MMF (P = .037); 44% showed global positive response. Of the KTRs, 16% experienced breakthrough infections, with 2 hospitalizations; prebreakthrough variant neutralization was poor. Absent neutralizing and CD8+ responses in KTRs indicate vulnerability to COVID-19 despite 3-dose mRNA vaccination. Lack of neutralization despite CD4+ expansion suggests B cell dysfunction and/or ineffective T cell help. Development of more effective KTR vaccine strategies is critical. (NCT04969263).

Methodological approaches to optimize multiplex oral fluid SARS-CoV-2 IgG assay performance and correlation with serologic and neutralizing antibody responses.

BACKGROUND: Oral fluid (hereafter, saliva) is a non-invasive and attractive alternative to blood for SARS-CoV-2 IgG testing; however, the heterogeneity of saliva as a matrix poses challenges for immunoassay performance. OBJECTIVES: To optimize performance of a magnetic microparticle-based multiplex immunoassay (MIA) for SARS-CoV-2 IgG measurement in saliva, with consideration of: i) threshold setting and validation across different MIA bead batches; ii) sample qualification based on salivary total IgG concentration; iii) calibration to U.S. SARS-CoV-2 serological standard binding antibody units (BAU); and iv) correlations with blood-based SARS-CoV-2 serological and neutralizing antibody (nAb) assays. METHODS: The salivary SARS-CoV-2 IgG MIA included 2 nucleocapsid (N), 3 receptor-binding domain (RBD), and 2 spike protein (S) antigens. Gingival crevicular fluid (GCF) swab saliva samples were collected before December 2019 (n = 555) and after molecular test-confirmed SARS-CoV-2 infection from 113 individuals (providing up to 5 repeated-measures; n = 398) and used to optimize and validate MIA performance (total n = 953). Combinations of IgG responses to N, RBD and S and total salivary IgG concentration (µg/mL) as a qualifier of nonreactive samples were optimized and validated, calibrated to the U.S. SARS-CoV-2 serological standard, and correlated with blood-based SARS-CoV-2 IgG ELISA and nAb assays. RESULTS: The sum of signal to cutoff (S/Co) to all seven MIA SARS-CoV-2 antigens and disqualification of nonreactive saliva samples with ≤15 µg/mL total IgG led to correct classification of 62/62 positives (sensitivity [Se] = 100.0%; 95% confidence interval [CI] = 94.8%, 100.0%) and 108/109 negatives (specificity [Sp] = 99.1%; 95% CI = 97.3%, 100.0%) at 8-million beads coupling scale and 80/81 positives (Se = 98.8%; 95% CI = 93.3%, 100.0%] and 127/127 negatives (Sp = 100%; 95% CI = 97.1%, 100.0%) at 20-million beads coupling scale. Salivary SARS-CoV-2 IgG crossed the MIA cutoff of 0.1 BAU/mL on average 9 days post-COVID-19 symptom onset and peaked around day 30. Among n = 30 matched saliva and plasma samples, salivary SARS-CoV-2 MIA IgG levels correlated with corresponding-antigen plasma ELISA IgG (N: ρ = 0.76, RBD: ρ = 0.83, S: ρ = 0.82; all p < 0.001). Correlations of plasma SARS-CoV-2 nAb assay area under the curve (AUC) with salivary MIA IgG (N: ρ = 0.68, RBD: ρ = 0.78, S: ρ = 0.79; all p < 0.001) and with plasma ELISA IgG (N: ρ = 0.76, RBD: ρ = 0.79, S: ρ = 0.76; p < 0.001) were similar. CONCLUSIONS: A salivary SARS-CoV-2 IgG MIA produced consistently high Se (> 98.8%) and Sp (> 99.1%) across two bead coupling scales and correlations with nAb responses that were similar to blood-based SARS-CoV-2 IgG ELISA data. This non-invasive salivary SARS-CoV-2 IgG MIA could increase engagement of vulnerable populations and improve broad understanding of humoral immunity (kinetics and gaps) within the evolving context of booster vaccination, viral variants and waning immunity.

The intersection of gender and race in older adults' decision to receive COVID-19 vaccines.

COVID-19 vaccines are essential public health tools for protecting older adults, who are at high risk of severe outcomes associated with COVID-19. Little is known, however, about how older adults approach the decision to receive a COVID-19 vaccine. We hypothesized that intersections between gender and race may provide unique insight into the decision-making process and the factors that lead to vaccine uptake among hesitant individuals. We performed in-depth interviews with 24 older adults who had been vaccinated against COVID-19 and used the framework approach with an intersectional lens to analyze data. Two typologies emerged: eager compliers did not question the need to vaccinate, whereas hesitant compliers were skeptical of the vaccine and underwent a thorough decision-making process prior to vaccination. For eager compliers, the vaccine offered protection from a disease that posed a serious threat, and few risks were perceived. In contrast, hesitant compliers perceived risks associated with the vaccine product or mistrusted the infrastructure that led to rapid vaccine development. Hesitancy was greater among Black participants, and only Black participants reported mistrust in vaccine infrastructure. At the intersection of gender and race, a 'White male effect' was observed, whereby White men perceived the fewest risks associated with the vaccine, and Black women were the most fearful of serious side effects. Nearly all hesitant compliers ultimately got vaccinated due to the threat of COVID-19. Convenient access through vaccine clinics in senior's buildings was pivotal for hesitant compliers and external and internal influences had differential impacts by race and gender. Emphasizing the risk of COVID-19, convenient and accessible opportunities for vaccination, and messages that are targeted to specific groups are likely to increase vaccine uptake among older adults.

Impact of Seasonal Coronavirus Antibodies on SARS-CoV-2 Vaccine Responses in Solid Organ Transplant Recipients.

Antibody responses to SARS-CoV-2 vaccination are reduced in solid organ transplant recipients (SOTRs). We report that increased levels of pre-existing antibodies to seasonal coronaviruses are associated with decreased antibody response to SARS-CoV-2 vaccination in SOTRs, supporting that antigenic imprinting modulates vaccine responses in this immunosuppressed population.

Endemic Human Coronavirus Antibody Levels Are Unchanged after Convalescent or Control Plasma Transfusion for Early Outpatient COVID-19 Treatment.

The impact of preexisting antibodies to the four endemic human coronaviruses (ehCoV) (229E, OC43, NL63, and HKU1) on severe (hospitalization) coronavirus disease 2019 (COVID-19) outcomes has been described in small cohorts. Many studies have measured ehCoV 229E, OC43, NL63, and HKU1 antibody levels weeks after recovery rather than in the first weeks of illness, which is more relevant to early hospitalizations. Antibody levels to the spike protein of the four coronaviruses (229E, OC43, NL63, and HKU1), as well as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were measured both before and immediately after convalescent or control plasma transfusion in 51 participants who were hospitalized and 250 who were not hospitalized, as well as in 71 convalescent and 50 control plasma donors as a subset from a completed randomized controlled trial. In COVID-19 convalescent plasma donors, the ehCoV spike antibodies were 1.2 to 2 times greater than the control donor unit levels, while donor COVID-19 convalescent plasma (CCP) SARS-CoV-2 spike antibodies were more than 600 times the control plasma units. Plasma transfusion, whether COVID-19 convalescent or control, did not alter the post-transfusion antibody levels for the endemic human coronaviruses (229E, OC43, NL63, and HKU1) in those hospitalized and not hospitalized, despite the 1.2- to 2-fold elevation in donor COVID-19 convalescent plasma. There was no influence of prior antibody levels to 229E, OC43, NL63, and HKU1 or post-transfusion antibody levels on subsequent hospitalization. These data, from a well-controlled prospective randomized clinical trial, add evidence that antibodies to ehCoV do not significantly impact COVID-19 outcomes, despite the apparent back-boosting of some ehCoV after SARS-CoV-2 infection. IMPORTANCE The relevance of preexisting immunity to the four endemic human coronaviruses in the first week of COVID-19 illness on the outcome of COVID-19 progression stems from the high prevalence of the ehCoV and SARS-CoV-2 coronaviruses. The question has been raised of whether therapeutic convalescent plasma or control plasma containing ehCoV antibodies might alter the outcome of COVID-19 progression to hospitalization. Here, we observed that plasma transfusion did not significantly change the preexisting ehCoV antibody levels. In over 50 hospitalized participants and 250 nonhospitalized participants, ehCoV antibody levels were comparable, without statistical differences. Antibody levels were stable over the more than 12 months of the intervention trial, with individual heterogeneity similar in hospitalized and nonhospitalized participants. The ehCoV antibodies in plasma transfusion did not alter the recipient preexisting antibody levels nor hasten the COVID-19 progression to hospitalization in this clinical trial data.

Reconsideration of Antinucleocapsid IgG Antibody as a Marker of SARS-CoV-2 Infection Postvaccination for Mild COVID-19 Patients.

Antinucleocapsid (anti-N) immunoglobulin G antibody responses were lower in plasma and oral fluid after severe acute respiratory syndrome coronavirus 2 infection in vaccinated patients compared with patients infected before vaccination or infected without vaccination. This raises questions about the long-term use of anti-N antibodies as a marker for natural infection for surveillance.

Analysis of Clinical Outcomes of Pregnant Patients Treated With Nirmatrelvir and Ritonavir for Acute SARS-CoV-2 Infection.

Importance: Pregnant people are at increased risk of poor outcomes due to infection with SARS-CoV-2, and there are limited therapeutic options available. Objective: To evaluate the clinical outcomes associated with nirmatrelvir and ritonavir used to treat SARS-CoV-2 infection in pregnant patients. Design, Setting, and Participants: This case series included pregnant patients who were diagnosed with SARS-CoV-2 infection, received nirmatrelvir and ritonavir, and delivered their offspring within the Johns Hopkins Health System between December 22, 2021, and August 20, 2022. Exposures: Treatment with nirmatrelvir and ritonavir for SARS-CoV-2 infection during pregnancy. Main Outcomes and Measures: Clinical characteristics and outcomes were ascertained through manual record review. Results: Forty-seven pregnant patients (median [range] age, 34 [22-43] years) were included in the study, and the median (range) gestational age of their offspring was 28.4 (4.3-39.6) weeks. Medication was initiated at a median (range) of 1 (0-5) day after symptom onset, and only 2 patients [4.3%] did not complete the course of therapy because of adverse effects. Thirty patients (63.8%) treated with nirmatrelvir and ritonavir had a comorbidity in addition to pregnancy that could be a risk factor for developing severe COVID-19. Twenty-five patients [53.2%] delivered after treatment with nirmatrelvir and ritonavir. Twelve of these patients [48.0%] underwent cesarean delivery, 9 [75.0%] of which were scheduled. Two of 47 patients [4.3%] were hospitalized for conditions related to preexisting comorbidities. Conclusions and Relevance: In this case series, pregnant patients who were treated with nirmatrelvir and ritonavir tolerated treatment well, although there was an unexpectedly high rate of cesarean deliveries. The lack of an increase in serious adverse effects affecting pregnant patients or offspring suggests that clinicians can use this drug combination to treat pregnant patients with SARS-CoV-2 infection.

Clinical trials for COVID-19 should include sex as a variable

The number of COVID-19 cases appears to be comparable between men and women, but the severity of disease and death is two times greater for men than for women. History, including the 1918 influenza pandemic, warned us that male biases in COVID-19 could occur. In this Viewpoint, we focus on biological explanations, with a forward look at why clinicians and biomedical researchers should consider sex as a biological variable that will affect treatment outcomes for COVID-19. There is a long history of not analyzing or reporting differences between women and men in the prophylactic or therapeutic treatment of infectious diseases. We seek to reverse this trend and call on investigators developing and testing therapeutic and prophylactic approaches for COVID-19 to design studies that are inclusive of male versus female differences in drug responses, immunotherapies, vaccines, and nonpharmacological interventions.

The intersection of gender and race in older adults’ decision to receive COVID-19 vaccines

COVID-19 vaccines are essential public health tools for protecting older adults, who are at high risk of severe outcomes associated with COVID-19. Little is known, however, about how older adults approach the decision to receive a COVID-19 vaccine. We hypothesized that intersections between gender and race may provide unique insight into the decision-making process and the factors that lead to vaccine uptake among hesitant individuals. We performed in-depth interviews with 24 older adults who had been vaccinated against COVID-19 and used the framework approach with an intersectional lens to analyze data. Two typologies emerged: eager compliers did not question the need to vaccinate, whereas hesitant compliers were skeptical of the vaccine and underwent a thorough decision-making process prior to vaccination. For eager compliers, the vaccine offered protection from a disease that posed a serious threat, and few risks were perceived. In contrast, hesitant compliers perceived risks associated with the vaccine product or mistrusted the infrastructure that led to rapid vaccine development. Hesitancy was greater among Black participants, and only Black participants reported mistrust in vaccine infrastructure. At the intersection of gender and race, a ‘White male effect’ was observed, whereby White men perceived the fewest risks associated with the vaccine, and Black women were the most fearful of serious side effects. Nearly all hesitant compliers ultimately got vaccinated due to the threat of COVID-19. Convenient access through vaccine clinics in senior’s buildings was pivotal for hesitant compliers and external and internal influences had differential impacts by race and gender. Emphasizing the risk of COVID-19, convenient and accessible opportunities for vaccination, and messages that are targeted to specific groups are likely to increase vaccine uptake among older adults.

Association of Frailty, Age, and Biological Sex With Severe Acute Respiratory Syndrome Coronavirus 2 Messenger RNA Vaccine-Induced Immunity in Older Adults.

BACKGROUND: Male sex and old age are risk factors for severe coronavirus disease 2019, but the intersection of sex and aging on antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has not been characterized. METHODS: Plasma samples were collected from older adults (aged 75-98 years) before and after 3 doses of SARS-CoV-2 mRNA vaccination, and from younger adults (aged 18-74 years) post-dose 2, for comparison. Antibody binding to SARS-CoV-2 antigens (spike protein [S], S receptor-binding domain, and nucleocapsid), functional activity against S, and live-virus neutralization were measured against the vaccine virus and the Alpha, Delta, and Omicron variants of concern (VOCs). RESULTS: Vaccination induced greater antibody titers in older females than in older males, with both age and frailty associated with reduced antibody responses in males but not females. Responses declined significantly in the 6 months after the second dose. The third dose restored functional antibody responses and eliminated disparities caused by sex, age, and frailty in older adults. Responses to the VOCs, particularly the Omicron variant, were significantly reduced relative to the vaccine virus, with older males having lower titers to the VOCs than older females. Older adults had lower responses to the vaccine and VOC viruses than younger adults, with greater disparities in males than in females. CONCLUSIONS: Older and frail males may be more vulnerable to breakthrough infections owing to low antibody responses before receipt of a third vaccine dose. Promoting third dose coverage in older adults, especially males, is crucial to protecting this vulnerable population.

Genetic and hormonal mechanisms underlying sex-specific immune responses in tuberculosis.

Tuberculosis (TB), the world's deadliest bacterial infection, afflicts more human males than females, with a male/female (M/F) ratio of 1.7. Sex disparities in TB prevalence, pathophysiology, and clinical manifestations are widely reported, but the underlying biological mechanisms remain largely undefined. This review assesses epidemiological data on sex disparity in TB, as well as possible underlying hormonal and genetic mechanisms that might differentially modulate innate and adaptive immune responses in males and females, leading to sex differences in disease susceptibility. We consider whether this sex disparity can be extended to the efficacy of vaccines and discuss novel animal models which may offer mechanistic insights. A better understanding of the biological factors underpinning sex-related immune responses in TB may enable sex-specific personalized therapies for TB.

Roadmap for Sex-Responsive Influenza and COVID-19 Vaccine Research in Older Adults.

Sex differences in the immune system are dynamic throughout the lifespan and contribute to heterogeneity in the risk of infectious diseases and the response to vaccination in older adults. The importance of the intersection between sex and age in immunity to viral respiratory diseases is clearly demonstrated by the increased prevalence and severity of influenza and COVID-19 in older males compared to older females. Despite sex and age biases in the epidemiology and clinical manifestations of disease, these host factors are often ignored in vaccine research. Here, we review sex differences in the immunogenicity, effectiveness, and safety of the influenza and COVID-19 vaccines in older adults and the impact of sex-specific effects of age-related factors, including chronological age, frailty, and the presence of comorbidities. While a female bias in immunity to influenza vaccines has been consistently reported, understanding of sex differences in the response to COVID-19 vaccines in older adults is incomplete due to small sample sizes and failure to disaggregate clinical trial data by both sex and age. For both vaccines, a major gap in the literature is apparent, whereby very few studies investigate sex-specific effects of aging, frailty, or multimorbidity. By providing a roadmap for sex-responsive vaccine research, beyond influenza and COVID-19, we can leverage the heterogeneity in immunity among older adults to provide better protection against vaccine-preventable diseases.

My story of sex, gender, and women's health in a pandemic.

After more than 20 years of studying sex differences in viral pathogenesis and immunity to vaccines, the COVID-19 pandemic provided me with a unique opportunity to raise awareness about biological sex differences. The scientific community and public, alike, embraced the clinical and epidemiological data and supported inquiries into how males are twice as likely to be hospitalized and die from COVID-19. Immunological changes associated with pregnancy also contribute to worse outcomes from COVID-19. Collectively, we are finding that inflammation is a critical mediator of worse outcomes for males and pregnant females. The pandemic gave me a platform to discuss and address sex differences on a bigger stage, but two decades of studies working with other viruses prepared me for this moment in history.

The Serological Sciences Network (SeroNet) for COVID-19: Depth and Breadth of Serology Assays and Plans for Assay Harmonization.

In October 2020, the National Cancer Institute (NCI) Serological Sciences Network (SeroNet) was established to study the immune response to COVID-19, and "to develop, validate, improve, and implement serological testing and associated technologies" (https://www.cancer.gov/research/key-initiatives/covid-19/coronavirus-research-initiatives/serological-sciences-network). SeroNet is comprised of 25 participating research institutions partnering with the Frederick National Laboratory for Cancer Research (FNLCR) and the SeroNet Coordinating Center. Since its inception, SeroNet has supported collaborative development and sharing of COVID-19 serological assay procedures and has set forth plans for assay harmonization. To facilitate collaboration and procedure sharing, a detailed survey was sent to collate comprehensive assay details and performance metrics on COVID-19 serological assays within SeroNet. In addition, FNLCR established a protocol to calibrate SeroNet serological assays to reference standards, such as the U.S. severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) serology standard reference material and first WHO international standard (IS) for anti-SARS-CoV-2 immunoglobulin (20/136), to facilitate harmonization of assay reporting units and cross-comparison of study data. SeroNet institutions reported development of a total of 27 enzyme-linked immunosorbent assay (ELISA) methods, 13 multiplex assays, and 9 neutralization assays and use of 12 different commercial serological methods. FNLCR developed a standardized protocol for SeroNet institutions to calibrate these diverse serological assays to reference standards. In conclusion, SeroNet institutions have established a diverse array of COVID-19 serological assays to study the immune response to SARS-CoV-2 and vaccines. Calibration of SeroNet serological assays to harmonize results reporting will facilitate future pooled data analyses and study cross-comparisons. IMPORTANCE SeroNet institutions have developed or implemented 61 diverse COVID-19 serological assays and are collaboratively working to harmonize these assays using reference materials to establish standardized reporting units. This will facilitate clinical interpretation of serology results and cross-comparison of research data.

Considering how biological sex impacts immune responses and COVID-19 outcomes.

A male bias in mortality has emerged in the COVID-19 pandemic, which is consistent with the pathogenesis of other viral infections. Biological sex differences may manifest themselves in susceptibility to infection, early pathogenesis, innate viral control, adaptive immune responses or the balance of inflammation and tissue repair in the resolution of infection. We discuss available sex-disaggregated epidemiological data from the COVID-19 pandemic, introduce sex-differential features of immunity and highlight potential sex differences underlying COVID-19 severity. We propose that sex differences in immunopathogenesis will inform mechanisms of COVID-19, identify points for therapeutic intervention and improve vaccine design and increase vaccine efficacy.

A Fourth Dose of COVID-19 Vaccine Does Not Induce Neutralization of the Omicron Variant Among Solid Organ Transplant Recipients With Suboptimal Vaccine Response.

BACKGROUND: Humoral responses to coronavirus disease 2019 (COVID-19) vaccines are attenuated in solid organ transplant recipients (SOTRs), necessitating additional booster vaccinations. The Omicron variant demonstrates substantial immune evasion, and it is unknown whether additional vaccine doses increase neutralizing capacity versus this variant of concern (VOC) among SOTRs. METHODS: Within an observational cohort, 25 SOTRs with low seroresponse underwent anti-severe acute respiratory syndrome coronavirus 2 spike and receptor-binding domain immunoglobulin (Ig)G testing using a commercially available multiplex ELISA before and after a fourth COVID-19 vaccine dose (D4). Surrogate neutralization (percent angiotensin-converting enzyme 2 inhibition [%ACE2i], range 0%-100% with >20% correlating with live virus neutralization) was measured against full-length spike proteins of the vaccine strain and 5 VOCs including Delta and Omicron. Changes in IgG level and %ACE2i were compared using the paired Wilcoxon signed-rank test. RESULTS: Anti-receptor-binding domain and anti-spike seropositivity increased post-D4 from 56% to 84% and 68% to 88%, respectively. Median (interquartile range) anti-spike antibody significantly increased post-D4 from 42.3 (4.9-134.2) to 228.9 (1115.4-655.8) World Health Organization binding antibody units. %ACE2i (median [interquartile range]) also significantly increased against the vaccine strain (5.8% [0%-16.8%] to 20.6% [5.8%-45.9%]) and the Delta variant (9.1% [4.9%-12.8%] to 17.1% [10.3%-31.7%]), yet neutralization versus Omicron was poor, did not increase post-D4 (4.1% [0%-6.9%] to 0.5% [0%-5.7%]), and was significantly lower than boosted healthy controls. CONCLUSIONS: Although a fourth vaccine dose increases anti-spike IgG and neutralizing capacity against many VOCs, some SOTRs may remain at high risk for Omicron infection despite boosting. Thus, additional protective interventions or alternative vaccination strategies should be urgently explored.

A bacterial extracellular vesicle-based intranasal vaccine against SARS-CoV-2 protects against disease and elicits neutralizing antibodies to wild-type and Delta variants.

Several vaccines have been introduced to combat the coronavirus infectious disease-2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Current SARS-CoV-2 vaccines include mRNA-containing lipid nanoparticles or adenoviral vectors that encode the SARS-CoV-2 Spike (S) protein of SARS-CoV-2, inactivated virus, or protein subunits. Despite growing success in worldwide vaccination efforts, additional capabilities may be needed in the future to address issues such as stability and storage requirements, need for vaccine boosters, desirability of different routes of administration, and emergence of SARS-CoV-2 variants such as the Delta variant. Here, we present a novel, well-characterized SARS-CoV-2 vaccine candidate based on extracellular vesicles (EVs) of Salmonella typhimurium that are decorated with the mammalian cell culture-derived Spike receptor-binding domain (RBD). RBD-conjugated outer membrane vesicles (RBD-OMVs) were used to immunize the golden Syrian hamster (Mesocricetus auratus) model of COVID-19. Intranasal immunization resulted in high titres of blood anti-RBD IgG as well as detectable mucosal responses. Neutralizing antibody activity against wild-type and Delta variants was evident in all vaccinated subjects. Upon challenge with live virus, hamsters immunized with RBD-OMV, but not animals immunized with unconjugated OMVs or a vehicle control, avoided body mass loss, had lower virus titres in bronchoalveolar lavage fluid, and experienced less severe lung pathology. Our results emphasize the value and versatility of OMV-based vaccine approaches.

Differences and disparities in seasonal influenza vaccine, acceptance, adverse reactions, and coverage by age, sex, gender, and race.

BACKGROUND: Influenza is a significant threat to public health worldwide. Despite the widespread availability of effective and generally safe vaccines, the acceptance and coverage of influenza vaccines are significantly lower than recommended. Sociodemographic variables are known to be potential predictors of differential influenza vaccine uptake and outcomes. OBJECTIVES: This review aims to (1) identify how sociodemographic characteristics such as age, sex, gender, and race may influence seasonal influenza vaccine acceptance and coverage; and (2) evaluate the role of these sociodemographic characteristics in differential adverse reactions among vaccinated individuals. METHODS: PubMed was used as the database to search for published literature in three thematic areas related to the seasonal influenza vaccine - vaccine acceptance, adverse reactions, and vaccine coverage. RESULTS: A total of 3249 articles published between 2010 and 2020 were screened and reviewed, of which 39 studies were included in this literature review. By the three thematic areas, 17 studies assessed vaccine acceptance, 8 studies focused on adverse reactions, and 14 examined coverage of the seasonal influenza vaccine. There were also two studies that focused on more than one of the areas of interest. CONCLUSION: Each of the four sociodemographic predictors - age, sex, race, and gender - were found to significantly influence vaccine acceptance, receipt and outcomes in this review.

Progression and Resolution of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection in Golden Syrian Hamsters.

To catalyze severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) research, including development of novel interventive and preventive strategies, the progression of disease was characterized in a robust coronavirus disease 2019 (COVID-19) animal model. In this model, male and female golden Syrian hamsters were inoculated intranasally with SARS-CoV-2 USA-WA1/2020. Groups of inoculated and mock-inoculated uninfected control animals were euthanized at 2, 4, 7, 14, and 28 days after inoculation to track multiple clinical, pathology, virology, and immunology outcomes. SARS-CoV-2-inoculated animals consistently lost body weight during the first week of infection, had higher lung weights at terminal time points, and developed lung consolidation per histopathology and quantitative image analysis measurements. High levels of infectious virus and viral RNA were reliably present in the respiratory tract at days 2 and 4 after inoculation, corresponding with widespread necrosis and inflammation. At day 7, when the presence of infectious virus was rare, interstitial and alveolar macrophage infiltrates and marked reparative epithelial responses (type II hyperplasia) dominated in the lung. These lesions resolved over time, with only residual epithelial repair evident by day 28 after inoculation. The use of quantitative approaches to measure cellular and morphologic alterations in the lung provides valuable outcome measures for developing therapeutic and preventive interventions for COVID-19 using the hamster COVID-19 model.

Adaptive immune responses in vaccinated patients with symptomatic SARS-CoV-2 Alpha infection.

Benchmarks for protective immunity from infection or severe disease after SARS-CoV-2 vaccination are still being defined. Here, we characterized virus neutralizing and ELISA antibody levels, cellular immune responses, and viral variants in 4 separate groups: healthy controls (HCs) weeks (early) or months (late) following vaccination in comparison with symptomatic patients with SARS-CoV-2 after partial or full mRNA vaccination. During the period of the study, most symptomatic breakthrough infections were caused by the SARS-CoV-2 Alpha variant. Neutralizing antibody levels in the HCs were sustained over time against the vaccine parent virus but decreased against the Alpha variant, whereas IgG titers and T cell responses against the parent virus and Alpha variant declined over time. Both partially and fully vaccinated patients with symptomatic infections had lower virus neutralizing antibody levels against the parent virus than the HCs, similar IgG antibody titers, and similar virus-specific T cell responses measured by IFN-γ. Compared with HCs, neutralization activity against the Alpha variant was lower in the partially vaccinated infected patients and tended to be lower in the fully vaccinated infected patients. In this cohort of breakthrough infections, parent virus neutralization was the superior predictor of breakthrough infections with the Alpha variant of SARS-CoV-2.