Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 ...recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination ('hybrid immunity') further augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-gamma) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/10.sup.6 cytokine-producing peripheral blood mononuclear cells PBMCs). Almost all vaccinated participants with no prior infection exhibited IFN-gamma, IL-2 and IFN-gamma+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-gamma, IL-2 and IFN-gamma+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-gamma but not IL2 or IFN-gamma+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-gamma, IL-2, and IFN-gamma+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background:
We sought to determine pre-infection correlates of immunity against SARS-CoV-2 post-vaccine infections.
Methods:
Serum and saliva samples from 176 BNT162b2-vaccinated adults in ...the Prospective Assessment of SARS-CoV-2 Seroconversion study were collected between October and December 2021 and assessed for serum and saliva levels of WT SARS-CoV-2 Spike (S)-specific IgG and IgA antibodies using a microsphere-based multiplex immunoassay. Serum samples were also assessed for neutralization activity against D614G, Delta (617.2), and Omicron BA.1 and BA.1.1 variants using a lentiviral pseudovirus neutralization assay. After the fall visit, participants reported all positive PCR and/or antigen tests for SARS-CoV-2. Duration, severity, and type of symptoms, as well as risk exposures and adherence to precautionary measures, were assessed by questionnaires during the spring 2022 visit.
Results:
Thirty-two participants (18.2%) had infections between December 7, 2021 and April 1, 2022. Pre-infection anti-S IgG antibody levels and neutralizing titers against BA.1 and BA.1.1 were higher in individuals that did not develop infection (p values 0.0098, 0.0313, and 0.021, respectively). No individuals with an anti-S level greater than 15,000 binding antibody units (BAU/ml) developed a post-vaccine infection.
Conclusion:
High serum anti-S IgG antibody levels, high neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against post-vaccine infections during the initial Omicron wave. BAU levels greater than 15,000 in the fall of 2021 were associated with complete protection during the initial Omicron wave.
This work was supported in whole, or in part, with federal funds from the Defense Health Program (HU00012020067, HU00012020094) and the Immunization Healthcare Branch (HU00012120104) of the Defense Health Agency, United States Department of Defense, and the National Institute of Allergy and Infectious Disease (HU00011920111), under Inter-Agency Agreement Y1-AI-5072.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies decay but persist 6 months postvaccination; lower levels of neutralizing titers persist against Delta than wild-type virus. Of ...227 vaccinated healthcare workers tested, only 2 experienced outpatient symptomatic breakthrough infections, despite 59/227 exhibiting serologic evidence of SARS-CoV-2 infection, defined as presence of nucleocapsid protein antibodies.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Despite increasing attention to HIV-related stigma within the DoD, to date, the majority of research has focused on civilians, up to half of whom report perceived or experienced ...stigma. However, military service members and retirees with HIV may be particularly vulnerable to stigma and its adverse correlates.
Methods
The current study utilized cross-sectional data collected within the U.S. Military HIV Natural History Study. Participants completed questionnaires, including the Center for Epidemiologic Studies Depression scale, the Short Form Health Survey, the Internalization Subscale of the HIV Stigma Scale, and a measure of stigma experienced in the past year. Experiences of stigma were dichotomized to indicate presence or absence. Linear and logistic regressions were used to examine associations between internalized stigma and psychosocial functioning. All analyses were adjusted for age, race, sex, marital status, military rank, and duty status (i.e., active duty or retired).
Results
The sample comprised 399 participants (93.5% male; 46.0% Black/African American; Mage: 50.8 ± 13.2 years; Mage at HIV diagnosis: 31.9 ± 8.2 years; 32.4% on active duty). The majority (94.4%) had an undetectable viral load at the time of the visit. Fourteen percent reported being teased, treated unfairly, or discriminated against in the past year due to their HIV status, and 8% reported discrimination specifically within healthcare. Adjusting for covariates, internalized stigma was associated with poor physical (p < .001) and overall mental (p < .001) health. Internalized stigma was also associated with greater odds of reporting elevated depression (p < .001).
Conclusion
In this sample of service members and retirees with HIV, a small but significant minority of participants reported experiencing stigma. Rates of stigma were lower than those observed in some civilian samples, though heterogeneity in sampling and methodology preclude direct comparisons. Internalized stigma was associated with poor physical and mental health, signaling a need for continued efforts to assess both experienced and internalized stigma. Future research should explore associations between stigma, ART adherence, and other metrics of health, such as CD4 count, substance use, and cardiometabolic risk.
Disclosures
All Authors: No reported disclosures.
SARS-CoV-2 is a recently emerged pandemic coronavirus (CoV) capable of causing severe respiratory illness. However, a significant number of infected people present as asymptomatic or ...pauci-symptomatic. In this prospective assessment of at-risk healthcare workers (HCWs) we seek to determine whether pre-existing antibody or T cell responses to previous seasonal human coronavirus (HCoV) infections affect immunological or clinical responses to SARS-CoV-2 infection or vaccination.
A cohort of 300 healthcare workers, confirmed negative for SARS-CoV-2 exposure upon study entry, will be followed for up to 1 year with monthly serology analysis of IgM and IgG antibodies against the spike proteins of SARS-CoV-2 and the four major seasonal human coronavirus - HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63. Participants will complete monthly questionnaires that ask about Coronavirus Disease 2019 (COVID-19) exposure risks, and a standardized, validated symptom questionnaire (scoring viral respiratory disease symptoms, intensity and severity) at least twice monthly and any day when any symptoms manifest. SARS-CoV-2 PCR testing will be performed any time participants develop symptoms consistent with COVID-19. For those individuals that seroconvert and/or test positive by SARS-CoV-2 PCR, or receive the SARS-CoV-2 vaccine, additional studies of T cell activation and cytokine production in response to SARS-CoV-2 peptide pools and analysis of Natural Killer cell numbers and function will be conducted on that participant's cryopreserved baseline peripheral blood mononuclear cells (PBMCs). Following the first year of this study we will further analyze those participants having tested positive for COVID-19, and/or having received an authorized/licensed SARS-CoV-2 vaccine, quarterly (year 2) and semi-annually (years 3 and 4) to investigate immune response longevity.
This study will determine the frequency of asymptomatic and pauci-symptomatic SARS-CoV-2 infection in a cohort of at-risk healthcare workers. Baseline and longitudinal assays will determine the frequency and magnitude of anti-spike glycoprotein antibodies to the seasonal HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63, and may inform whether pre-existing antibodies to these human coronaviruses are associated with altered COVID-19 disease course. Finally, this study will evaluate whether pre-existing immune responses to seasonal HCoVs affect the magnitude and duration of antibody and T cell responses to SARS-CoV-2 vaccination, adjusting for demographic covariates.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
The relationship between postvaccination symptoms and strength of antibody responses is unclear. The goal of this study was to determine whether adverse effects caused by ...vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels.
Methods
We conducted a single-center, observational cohort study consisting of generally healthy adult participants that were not severely immunocompromised, had no history of coronavirus disease 2019, and were seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein before vaccination. Severity of vaccine-associated symptoms was obtained through participant-completed questionnaires. Testing for immunoglobulin G antibodies against SARS-CoV-2 spike protein and receptor-binding domain was conducted using microsphere-based multiplex immunoassays performed on serum samples collected at monthly visits. Neutralizing antibody titers were determined by microneutralization assays.
Results
Two hundred six participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers 1 month after vaccination. We also observed that (1) postvaccination symptoms were inversely correlated with age and weight and more common in women, (2) systemic symptoms were more frequent after the second vaccination, (3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and (4) older age was associated with lower titers.
Conclusions
Lack of postvaccination symptoms after receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies 1 month after vaccination.
We found no correlation between BNT162b2-associated symptom severity and vaccine-induced antibody titers 1 month after vaccination. Adverse effects inversely correlated with age and weight, whereas symptom severity after first vaccination was predictive of that after second vaccination.
We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States.
Serum and saliva samples ...from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires.
Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range.
In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.
Abstract
Background
We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine infections.
Methods
Serum and saliva samples from 176 BNT162b2-vaccinated adults in ...the Prospective Assessment of SARS-CoV-2 Seroconversion study were collected between October and December 2021 and assessed for serum and saliva levels of ancestral (WT) SARS-CoV-2 Spike (S)-specific IgG and IgA binding antibodies (bAb), and serum levels of Omicron BA.1 subvariant S-specific IgG bAb using a multiplex microsphere-based immunoassay. Serum samples were also assessed for WT S-specific bAb by two commercial assays, and neutralization activity against D614G, Delta (617.2), and Omicron BA.1 and BA.1.1 subvariants using a lentiviral pseudovirus neutralization assay. After the fall 2021 visit, participants reported all positive PCR and/or antigen tests for SARS-CoV-2. Duration, severity, and type of symptoms, as well as risk exposures and adherence to precautionary measures, were assessed by questionnaires during the spring 2022 visit.
Results
Thirty-two participants (18.2%) developed post-vaccination infections (PVI) between December 7, 2021 and April 1, 2022. Pre-infection WT and BA.1 anti-S IgG bAb levels measured by MMIA and neutralizing titers (NT) against BA.1 and BA.1.1 were significantly higher in individuals that did not develop PVIs. WT anti-S IgG bAb levels greater than 5,000 binding antibody units/ml were associated with substantial protection against symptomatic PVI.
Conclusion
Anti-S IgG bAb levels (directed against either WT or BA.1) and NT IgG titers both serve as correlates of protection against symptomatic PVI, with high levels associated with both protection against symptomatic infection and reduced severity of disease in those who develop PVI. Results of this study also suggest that commercial assays for anti-S bAb may need to be reformatted to enable detection of higher maximum values for use as predictors of increased susceptibility to SARS-CoV-2 infection.
Disclosures
David Tribble, MD, DrPH, AstraZeneca: The IDCRP and HJF were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial as part of US Govt COVID response Timothy Burgess, MD, MPH, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial Simon Pollett, MBBS, AstraZeneca: The IDCRP and the Henry M. Jackson Foundation (HJF) were funded to conduct an unrelated phase III COVID-19 monoclonal antibody immunoprophylaxis trial
Abstract
Background
We sought to determine the frequency of asymptomatic SARS-CoV-2 infections, the BNT162b2 mRNA COVID 19 vaccine-related symptoms, and the correlates of immunity in post-vaccination ...breakthrough infections in a prospective cohort of healthcare workers.
Methods
We have been conducting a single-center, observational cohort study of healthcare workers. 271 participants were enrolled since August 25, 2020. Testing for SARS-CoV-2 spike (S)-specific IgG antibodies is conducted using a microsphere-based multiplex immunoassay interpolated against an internal standard curve for binding antibody (bAb) units (BAU) and has been performed on serum samples collected at monthly visits between September 2020 to August of 2021, and quarterly since then. Neutralizing antibody titers against wild-type (WT) virus are determined by microneutralization assays and against Delta and Omicron variants by lentiviral pseudovirus neutralization assays. For the first 6 months, participants completed a symptoms questionnaire every day they had any symptoms.
Results
12 participants were diagnosed with SARS-CoV-2, with at least mild symptoms. Of 206 participants evaluated for adverse effects after 1st and 2nd vaccine doses, no relationship was observed between vaccine-associated symptom scores and antibody titers 1 month after the 2nd dose. Longitudinal studies demonstrate that anti-S IgG bAbs decrease from a geometric mean (GM) of 1929 BAU/mL at 1 month post-vaccination to a GM of 442 BAU/mL at 6 months post-vaccination (P< 0.001, n=187), and that boosting increases S-specific IgG BAU. While only 5 of 39 participants had detectable anti-Omicron neutralizing activity 1 month after 2 vaccinations, booster vaccination resulted in detectable neutralizing activity for all participants.
Conclusion
Asymptomatic infection is likely rare, that there is no relationship between vaccine-associated symptom severity and antibody titers 1 month after the 2nd vaccination, and that booster results in better protection against the Omicron variant. Ongoing studies are evaluating serological and cellular immune responses immediately prior to 38 breakthrough infections in an attempt to identify immune correlates of protection and will be reported at the conference.
Disclosures
John H. Powers, III, MD, Arrevus: Advisor/Consultant|Eicos: Advisor/Consultant|Evofem: Advisor/Consultant|Eyecheck: Advisor/Consultant|Gilead: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|OPKO: Advisor/Consultant|Resolve: Advisor/Consultant|Romark: Advisor/Consultant|SpineBioPharma: Advisor/Consultant|UTIlity: Advisor/Consultant|Vir: Advisor/Consultant David Tribble, MD, DrPH, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Simon Pollett, MBBS, Astra Zeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response Timothy Burgess, MD, MPH, AstraZeneca: The HJF, in support of the USU IDCRP, was funded to conduct or augment unrelated Phase III Mab and vaccine trials as part of US Govt. COVID19 response.
Abstract
Background
The Prospective Assessment of SARS-CoV-2 Seroconversion (PASS) study is following over 200 healthcare workers who have received the Pfizer-BioNTech BNT162b2 COVID-19 mRNA vaccine. ...A major aim of the study is to determine whether baseline antibody titers against the seasonal human coronaviruses are associated with altered levels of vaccine-induced antibody responses to SARS-CoV-2.
Methods
Serial serum samples obtained pre-vaccination and 1 month after the second dose were tested for IgG antibodies against the full pre-fusion spike protein and the receptor binding domain (RBD) of SARS-CoV-2, as well as the full pre-fusion spike proteins of OC43, HKU1, 229E, and NL63. Antibodies were measured using highly sensitive and specific multiplex assays based on Luminex-xMAP technology.
Results
Preliminary analyses of the first 103 subjects in whom we have 1 month post-vaccination serum demonstrate development of high IgG geometric mean titers (GMT) to both the full spike protein (GMT: 13,685, 12,014-15,589, 95% CI) and the RBD (GMT: 19,448, 17,264-21,908, 95% CI) of SARS-CoV-2 after the 2nd vaccine dose. Preliminary analysis demonstrates no association between baseline antibody titers against spike protein of OC43 and antibody titers against SARS-CoV-2 spike protein (Pearson’s r-value= 0.13, P-value= 0.21) or RBD (Pearson’s r-value= 0.09, P-value= 0.36) one month after vaccination. Future analyses will evaluate whether there is an association with baseline seasonal coronavirus antibody titers and either SARS-CoV-2 neutralization titers or anti-SARS-CoV-2 spike protein titers at 6 months after vaccination.
Conclusion
These preliminary results suggest that baseline antibody responses to seasonal coronaviruses neither boost nor impede SARS-CoV-2 vaccine-induced antibody responses. Longitudinal sampling will enable assessment of vaccine durability and determination of whether baseline seasonal coronavirus antibody levels are associated with altered duration of detectable COVID-19 vaccine-induced antibody responses.
Disclosures
Simon Pollett, MBBS, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work)) David Tribble, M.D., DrPH, Astra Zeneca (Other Financial or Material Support, HJF, in support of USU IDCRP, funded under a CRADA to augment the conduct of an unrelated Phase III COVID-19 vaccine trial sponsored by AstraZeneca as part of USG response (unrelated work))
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