Antibodies elicited by SARS-CoV-2 infection or mRNA vaccines have reduced neutralizing activity against Beta and Omicron pseudoviruses

Multiple severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. Although the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.1.529) spike protein appear to diminish the protection conferred by pre-existing immunity. Using vesicular stomatitis virus (VSV) pseudoparticles expressing the spike protein of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in individuals after infection and in mRNA-vaccinated individuals. We observed that boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta, and Omicron variants; however, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses whereas responses may have been reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

Postmortem high-dimensional immune profiling of severe COVID-19 patients reveals distinct patterns of immunosuppression and immunoactivation

A complete diagnostic autopsy is the gold-standard to gain insight into Coronavirus disease 2019 (COVID-19) pathogenesis. To delineate the in situ immune responses to SARS-CoV-2 viral infection, here we perform comprehensive high-dimensional transcriptional and spatial immune profiling in 22 COVID-19 decedents from Wuhan, China. We find TIM-3-mediated and PD-1-mediated immunosuppression as a hallmark of severe COVID-19, particularly in men, with PD-1+ cells being proximal rather than distal to TIM-3+ cells. Concurrently, lymphocytes are distal, while activated myeloid cells are proximal, to SARS-CoV-2 viral antigens, consistent with prevalent SARS-CoV-2 infection of myeloid cells in multiple organs. Finally, viral load positively correlates with specific immunosuppression and dendritic cell markers. In summary, our data show that SARS-CoV-2 viral infection induces lymphocyte suppression yet myeloid activation in severe COVID-19, so these two cell types likely have distinct functions in severe COVID-19 disease progression, and should be targeted differently for therapy.

A bispecific monomeric nanobody induces spike trimer dimers and neutralizes SARS-CoV-2 in vivo

Antibodies binding to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike have therapeutic promise, but emerging variants show the potential for virus escape. This emphasizes the need for therapeutic molecules with distinct and novel neutralization mechanisms. Here we describe the isolation of a nanobody that interacts simultaneously with two RBDs from different spike trimers of SARS-CoV-2, rapidly inducing the formation of spike trimer–dimers leading to the loss of their ability to attach to the host cell receptor, ACE2. We show that this nanobody potently neutralizes SARS-CoV-2, including the beta and delta variants, and cross-neutralizes SARS-CoV. Furthermore, we demonstrate the therapeutic potential of the nanobody against SARS-CoV-2 and the beta variant in a human ACE2 transgenic mouse model. This naturally elicited bispecific monomeric nanobody establishes an uncommon strategy for potent inactivation of viral antigens and represents a promising antiviral against emerging SARS-CoV-2 variants.

Extracellular Vesicles as a New Promising Therapy in HIV Infection

Combination antiretroviral therapy (cART) effectively blocks HIV replication but cannot completely eliminate HIV from the body mainly due to establishment of a viral reservoir. To date, clinical strategies designed to replace cART for life and alternatively to eliminate the HIV reservoir have failed. The reduced expression of viral antigens in the latently infected cells is one of the main reasons behind the failure of the strategies to purge the HIV reservoir. This situation has forced the scientific community to search alternative therapeutic strategies to control HIV infection. In this regard, recent findings have pointed out extracellular vesicles as therapeutic agents with enormous potential to control HIV infection. This review focuses on their role as pro-viral and anti-viral factors, as well as their potential therapeutic applications.

Magnitude and breadth of neutralizing antibody responses elicited by SARS-CoV-2 infection or vaccination

Multiple SARS-CoV-2 variants that possess mutations associated with increased transmission and antibody escape have arisen over the course of the current pandemic. While the current vaccines have largely been effective against past variants, the number of mutations found on the Omicron (B.1.529) spike appear to diminish the efficacy of pre-existing immunity. Using pseudoparticles expressing the spike of several SARS-CoV-2 variants, we evaluated the magnitude and breadth of the neutralizing antibody response over time in naturally infected and in mRNA-vaccinated individuals. We observed that while boosting increases the magnitude of the antibody response to wildtype (D614), Beta, Delta and Omicron variants, the Omicron variant was the most resistant to neutralization. We further observed that vaccinated healthy adults had robust and broad antibody responses while responses were relatively reduced in vaccinated pregnant women, underscoring the importance of learning how to maximize mRNA vaccine responses in pregnant populations. Findings from this study show substantial heterogeneity in the magnitude and breadth of responses after infection and mRNA vaccination and may support the addition of more conserved viral antigens to existing SARS-CoV-2 vaccines.

ANALISIS PENGETAHUAN TENTANG PENCEGAHAN PENYEBARAN COVID-19 DENGAN KECEMASAN IBU MEMBAWA BAYI IMUNISASI DI KLINIK PRATAMA NINING PELAWATI

Corona virus disease (COVID-19) has an impact on health and health services, one of which is maternal anxiety in bringing babies for immunization, immunization is a specific passive effort (inserting bacterial or viral antigens of diseases that have been weakened or killed into the body to form antibodies (immune substances) against a disease. Due to immunization there is a decrease in immunization coverage. This study uses an analytical descriptive research design to analyze Knowledge About Prevention of the Spread of Covid-19 With Anxiety of Mothers Carrying Immunized Babies at the Pratama Nining Pelawati Clinic. The population in this study was all 35 mothers who have babies visited the nining clinic. The sample was taken using total sampling. The results showed that the majority of respondents had less knowledge about preventing the spread of Covid-19 when carrying immunized babies, namely 20 respondents (57 ,1%), 19 respondents (54.3%) respondents had severe anxiety when carrying immunized babies. statistical test, it can be seen that there is a relationship between knowledge about the prevention of the spread of Covid-19 and the anxiety of mothers carrying baby immunizations at the Nining Pelawati Pratama Clinic with p = 0.005 (p <0.05). It is hoped that midwives will cooperate with the COVID-19 task force in spreading correct information about the spread of COVID-19.

CHARACTERISTICS OF VIRAL ANTIGENS AND MICROBIAL SPECTRUM OF UPPER AND LOWER RESPIRATORY TRACT IN INFANTS WITH BRONCHITIS

Introduction. The difficulty in diagnosing different clinical forms of bronchitis is due to the fact that their clinical manifestations have a number of similar symptoms, despite the fact that these diseases may be as-sociated with different forms according to the classification. Diagnosis can be often complicated by the pre-disposition of very young children to recurrent respiratory diseases, which often mark the formation of a pro-longed and recurrent course of the disease caused by viral and bacterial contamination of the respiratory tract. The aim of this study is to investigate viral and microbial contamination of the respiratory tract in vari-ous clinical forms of bronchitis of infants and to clarify their etiological significance in parallel with the as-sessment of the intestinal microflora. Materials and methods. 578 children aged from 6 months to 3 years with various clinical forms of bronchitis were monitored. Virological examination was performed by the direct Coons method, which detected viral antigens in the cells of the mucous membrane of the lower nasal si-nuses. Bacteriological examination was performed by bacterial inoculation of nasopharyngeal mucus, spu-tum and feces in a nutrient medium. Results. Clinical and laboratory examination of young infants made it possible to identify the influence of detected viral antigens and pathogenic microflora in the throat, sputum and feces on the formation of various clinical forms of bronchitis and their clinical peculiarities not only in the period of exacerbation, but also in a remission period that indicates the persistence of viruses and bacteria. Conclusion. Detection of viral antigens, dysbiosis and microbial aggression of the upper and lower respira-tory tract gives grounds for substantiating the indications for staged rehabilitation therapy for infants with various clinical forms of bronchitis.

Epidemiological and Immunological Features of Obesity and SARS-CoV-2

Obesity is a key correlate of severe SARS-CoV-2 outcomes while the role of obesity on risk of SARS-CoV-2 infection, symptom phenotype, and immune response remain poorly defined. We examined data from a prospective SARS-CoV-2 cohort study to address these questions. Serostatus, body mass index, demographics, comorbidities, and prior COVID-19 compatible symptoms were assessed at baseline and serostatus and symptoms monthly thereafter. SARS-CoV-2 immunoassays included an IgG ELISA targeting the spike RBD, multiarray Luminex targeting 20 viral antigens, pseudovirus neutralization, and T cell ELISPOT assays. Our results from a large prospective SARS-CoV-2 cohort study indicate symptom phenotype is strongly influenced by obesity among younger but not older age groups; we did not identify evidence to suggest obese individuals are at higher risk of SARS-CoV-2 infection; and remarkably homogenous immune activity across BMI categories suggests immune protection across these groups may be similar.