ABSTRACT
Although vaccines effectively prevent COVID-19 in healthy individuals, they appear less immunogenic in individuals with chronic inflammatory diseases (CID) and/or under chronic immunosuppression, and there is uncertainty of their activity against emerging variants of concern in this population. Here, we assessed a cohort of 74 CID patients treated as monotherapy with chronic immunosuppressive drugs for functional antibody responses in serum against historical and variant SARS-CoV-2 viruses after immunization with Pfizer mRNA BNT162b2 vaccine. Longitudinal analysis showed the greatest reductions in neutralizing antibodies and Fc effector function capacity in individuals treated with TNF- inhibitors, and this pattern appeared worse against the B.1.617.2 Delta virus. Within five months of vaccination, serum neutralizing titers of the majority of CID patients fell below the presumed threshold correlate for antibody-mediated protection. Thus, further vaccine boosting or administration of long-acting prophylaxis (e.g., monoclonal antibodies) likely will be required to prevent SARS-CoV-2 infection in this susceptible population.
Subject(s)
COVID-19 , Chronic DiseaseABSTRACT
The introduction of vaccines has inspired new hope in the battle against SARS-CoV-2. However, the emergence of viral variants, in the absence of potent antivirals, has left the world struggling with the uncertain nature of this disease. Antibodies currently represent the strongest correlate of immunity against COVID-19, thus we profiled the earliest humoral signatures in a large cohort of severe and asymptomatic COVID-19 individuals. While a SARS-CoV-2-specific immune response evolved rapidly in survivors of COVID-19, non-survivors exhibited blunted and delayed humoral immune evolution, particularly with respect to S2-specific antibody evolution. Given the conservation of S2 across {beta}-coronaviruses, we found the early development of SARS-CoV-2-specific immunity occurred in tandem with pre-existing common {beta}-coronavirus OC43 humoral immunity in survivors, which was selectively also expanded in individuals that develop paucisymptomatic infection. These data point to the importance of cross-coronavirus immunity as a correlate of protection against COVID-19.
Subject(s)
COVID-19ABSTRACT
Adjuvanted soluble protein vaccines have been used extensively in humans for protection against various viral infections based on their robust induction of antibody responses. Here, soluble prefusion-stabilized spike trimers (preS dTM) from the severe acute respiratory syndrome coronavirus (SARS-CoV-2) were formulated with the adjuvant AS03 and administered twice to nonhuman primates (NHP). Binding and functional neutralization assays and systems serology revealed that NHP developed AS03-dependent multi-functional humoral responses that targeted multiple spike domains and bound to a variety of antibody FC receptors mediating effector functions in vitro. Pseudovirus and live virus neutralizing IC50 titers were on average greater than 1000 and significantly higher than a panel of human convalescent sera. NHP were challenged intranasally and intratracheally with a high dose (3x106 PFU) of SARS-CoV-2 (USA-WA1/2020 isolate). Two days post-challenge, vaccinated NHP showed rapid control of viral replication in both the upper and lower airways. Notably, vaccinated NHP also had increased spike-specific IgG antibody responses in the lung as early as 2 days post challenge. Moreover, vaccine-induced IgG mediated protection from SARS-CoV-2 challenge following passive transfer to hamsters. These data show that antibodies induced by the AS03-adjuvanted preS dTM vaccine are sufficient to mediate protection against SARS-CoV-2 and support the evaluation of this vaccine in human clinical trials.
Subject(s)
Severe Acute Respiratory SyndromeABSTRACT
The development of a portfolio of SARS-CoV-2 vaccines to vaccinate the global population remains an urgent public health imperative. Here, we demonstrate the capacity of a subunit vaccine under clinical development, comprising the SARS-CoV-2 Spike protein receptor-binding domain displayed on a two-component protein nanoparticle (RBD-NP), to stimulate robust and durable neutralizing antibody (nAb) responses and protection against SARS-CoV-2 in non-human primates. We evaluated five different adjuvants combined with RBD-NP including Essai O/W 1849101, a squalene-in-water emulsion; AS03, an alpha-tocopherol-containing squalene-based oil-in-water emulsion used in pandemic influenza vaccines; AS37, a TLR-7 agonist adsorbed to Alum; CpG 1018-Alum (CpG-Alum), a TLR-9 agonist formulated in Alum; or Alum, the most widely used adjuvant. All five adjuvants induced substantial nAb and CD4 T cell responses after two consecutive immunizations. Durable nAb responses were evaluated for RBD-NP/AS03 immunization and the live-virus nAb response was durably maintained up to 154 days post-vaccination. AS03, CpG-Alum, AS37 and Alum groups conferred significant protection against SARS-CoV-2 infection in the pharynges, nares and in the bronchoalveolar lavage. The nAb titers were highly correlated with protection against infection. Furthermore, RBD-NP when used in conjunction with AS03 was as potent as the prefusion stabilized Spike immunogen, HexaPro. Taken together, these data highlight the efficacy of the RBD-NP formulated with clinically relevant adjuvants in promoting robust immunity against SARS-CoV-2 in non-human primates.
Subject(s)
COVID-19ABSTRACT
Recently approved vaccines have already shown remarkable protection in limiting SARS-CoV-2 associated disease. However, immunologic mechanism(s) of protection, as well as how boosting alters immunity to wildtype and newly emerging strains, remain incompletely understood. Here we deeply profiled the humoral immune response in a cohort of non-human primates immunized with a stable recombinant full-length SARS-CoV-2 spike (S) glycoprotein (NVX-CoV2373) at two dose levels, administered as a single or two-dose regimen with a saponin-based adjuvant Matrix-M. While antigen dose had some effect on Fc-effector profiles, both antigen dose and boosting significantly altered overall titers, neutralization and Fc-effector profiles, driving unique vaccine-induced antibody fingerprints. Combined differences in antibody effector functions and neutralization were strongly associated with distinct levels of protection in the upper and lower respiratory tract, pointing to the presence of combined, but distinct, compartment-specific neutralization and Fc-mechanisms as key determinants of protective immunity against infection. Moreover, NVX-CoV2373 elicited antibodies functionally target emerging SARS-CoV-2 variants, collectively pointing to the critical collaborative role for Fab and Fc in driving maximal protection against SARS-CoV-2. Collectively, the data presented here suggest that a single dose may prevent disease, but that two doses may be essential to block further transmission of SARS-CoV-2 and emerging variants.
ABSTRACT
Background: Obesity is established as a key correlate of severe SARS-CoV-2 outcomes. Multiple other epidemiological and immunological features are less well-defined including whether obesity increases susceptibility to SARS-CoV-2, influences symptom phenotype, or impedes or alters the immune response to infection. Given the substantial global burden of obesity and given these uncertainties, we examined the epidemiology and immunology of obesity and SARS-CoV-2. Methods: Industry employees were invited to participate in a prospective SARS-CoV-2 serology-based cohort study. Blood and baseline survey measures that included demographics, comorbidities, and prior COVID-19 compatible symptoms were collected. Serological testing and interim symptom reporting were conducted monthly. 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. Unadjusted and adjusted analyses were used to identify differences in seroprevalence, clinical features, and immune parameters by BMI. Results: Of 4469 individuals enrolled, 322 (7.21%) were seropositive. Adjusted seroprevalence was non-significantly lower with higher BMI. Obesity was associated with increased reporting of fever (OR 3.43 [95% CI 1.58-7.60]) and multiple other symptoms and aggregate measures. There were no identifiable differences in immune response between obese and non-obese individuals. Discussion: We present benchmark data that obesity is not linked to increased risk of SARS-CoV-2 infection; that symptom phenotype is strongly influenced by obesity; and that despite evidence of obesity-associated immune dysregulation in severe infections, there is no evidence of muted or dysfunctional immune response across multiple immune measures among non-severe infections.
Subject(s)
COVID-19 , Obesity , Fever , Sexual Dysfunction, PhysiologicalABSTRACT
ObjectivesTo identify the level of Mental Health Status of Adolescents During the COVID-19 Pandemic among the Bangladeshi Graduate Student at Dhaka MethodA cross-sectional survey was conducted with 330 students from different public and Private Universities in Dhaka, Bangladesh between April 01, 2020 and July 31, 2020 amid the COVID-19 lockdown period in Bangladesh. A standard, self-administered online questionnaire consisting of questions on socio-demographic variables, mental health status, as well as stress management sent to the respondents through social networking platforms. Data were analyzed using descriptive statistics, t-test, one-way ANOVA and correlation tests. ResultsThe mean score of mental health status was 2.08 based on four points scale. They felt problem in decision making (3.04), in doing the things well (2.92), in enjoying normal day to day life (2.88), in playing a useful part in life (2.85), in doing their task (2.75), living in perfectly well and in good health (2.70). The respondents also developed a suicidal tendency (2.55), felt nervous in strung-up (2.24), took longer time to do things (2.14), felt tightness and pressure in head (2.12), and found themselves pressurized by various stuff (2.05). This study also found a significant positive relationship between mental health status and age, living with parents, and parents attitude. Finally, this study revealed that the respondents managed their stress by chatting with their friends, parents and siblings, and by sleeping. ConclusionMental health status of adolescents was found moderate in this study. This study suggests further large-scale study including different socio-economic settings in order to figure out the real scenario of adolescents mental health status of the country during the pandemic.
Subject(s)
COVID-19ABSTRACT
The COVID-19 pandemic in the U.S. has exhibited distinct waves, the first beginning in March 2020, the second beginning in early June, and additional waves currently emerging. Paradoxically, almost no county has exhibited this multi-wave pattern. We aim to answer three research questions: (1) How many distinct clusters of counties exhibit similar COVID-19 patterns in the time-series of daily confirmed cases?; (2) What is the geographic distribution of the counties within each cluster? and (3) Are county-level demographic, socioeconomic and political variables associated with the COVID-19 case patterns? We analyzed data from counties in the U.S. from March 1 to October 24, 2020. Time series clustering identified clusters in the daily confirmed cases of COVID-19. An explanatory model was used to identify demographic, socioeconomic and political variables associated the cluster patterns. Four patterns were identified from the timing of the outbreaks including counties experiencing a spring, an early summer, a late summer, and a fall outbreak. Several county-level demographic, socioeconomic, and political variables showed significant associations with the identified clusters. The timing of the outbreak is related both to the geographic location within the U.S. and several variables including age, poverty distribution, and political association. These results show that the reported pattern of cases in the U.S. is observed through aggregation of the COVID-19 cases, suggesting that local trends may be more informative. The timing of the outbreak varies by county, and is associated with important demographic, socioeconomic and geographic factors.