scholarly journals Long-term SARS-CoV-2 RNA shedding and its temporal association to IgG seropositivity

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Vineet Agarwal ◽  
A. J. Venkatakrishnan ◽  
Arjun Puranik ◽  
Christian Kirkup ◽  
Agustin Lopez-Marquez ◽  
...  
Keyword(s):  
Upper Bound ◽  
Neutralizing Antibody ◽  
Initial Diagnosis ◽  
Viral Rna ◽  
Temporal Association ◽  
Diagnostic Assays ◽  
Viral Loads ◽  
Antibody Titers ◽  
The Mean

AbstractLongitudinal characterization of SARS-CoV-2 PCR testing from COVID-19 patient’s nasopharynx and its juxtaposition with blood-based IgG-seroconversion diagnostic assays is critical to understanding SARS-CoV-2 infection durations. Here, we retrospectively analyze 851 SARS-CoV-2-positive patients with at least two positive PCR tests and find that 99 of these patients remain SARS-CoV-2-positive after 4 weeks from their initial diagnosis date. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95% CI: 34.3–41.3). Our findings from juxtaposing IgG and PCR tests thus reveal that some SARS-CoV-2-positive patients are non-hospitalized and seropositive, yet actively shed viral RNA (14 of 90 patients). This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term non-hospitalized shedders as a means of characterizing the SARS-CoV-2 infection lifecycle.

scholarly journals Long-term SARS-CoV-2 RNA Shedding and its Temporal Association to IgG Seropositivity

2020 ◽  
Author(s):  
Vineet Agarwal ◽  
AJ Venkatakrishnan ◽  
Arjun Puranik ◽  
Christian Kirkup ◽  
Agustin Lopez-Marquez ◽  
...  
Keyword(s):  
Upper Bound ◽  
Neutralizing Antibody ◽  
Initial Diagnosis ◽  
Viral Rna ◽  
Temporal Association ◽  
Viral Loads ◽  
Antibody Titers ◽  
The Mean

Analysis of 851 COVID-19 patients with a SARS-CoV-2-positive PCR at follow-up shows 99 patients remained SARS-CoV-2-positive after four weeks from initial diagnosis. Surprisingly, a majority of these long-term viral RNA shedders were not hospitalized (61 of 99), with variable PCR Crossing point values over the month post diagnosis. For the 851-patient cohort, the mean lower bound of viral RNA shedding was 17.3 days (SD: 7.8), and the mean upper bound of viral RNA shedding from 668 patients transitioning to confirmed PCR-negative status was 22.7 days (SD: 11.8). Among 104 patients with an IgG test result, 90 patients were seropositive to date, with mean upper bound of time to seropositivity from initial diagnosis being 37.8 days (95%CI: 34.3-41.3). Juxtaposing IgG/PCR tests revealed that 14 of 90 patients are non-hospitalized and seropositive yet shed viral RNA. This study emphasizes the need for monitoring viral loads and neutralizing antibody titers in long-term shedders.

scholarly journals Soluble Spike DNA Vaccine Provides Long-Term Protective Immunity against SARS-CoV-2 in Mice and Nonhuman Primates

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 307
Author(s):  
Yong Bok Seo ◽  
You Suk Suh ◽  
Ji In Ryu ◽  
Hwanhee Jang ◽  
Hanseul Oh ◽  
...  
Keyword(s):  
T Cell ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Dependent Manner ◽  
Viral Loads ◽  
Cell Responses ◽  
Rapid Spread

The unprecedented and rapid spread of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19-vaccinated nonhuman primates seroconverted rapidly and exhibited a detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they had reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides a durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2.

scholarly journals Soluble Spike DNA vaccine provides long-term protective immunity against SAR-CoV-2 in mice and nonhuman primates

2020 ◽  
Author(s):  
Yong Bok Seo ◽  
You Suk Suh ◽  
Ji In Ryu ◽  
Hwanhee Jang ◽  
Hanseul Oh ◽  
...  
Keyword(s):  
T Cell ◽  
Nonhuman Primates ◽  
Vaccine Candidate ◽  
T Cell Responses ◽  
Neutralizing Antibody ◽  
Dependent Manner ◽  
Viral Loads ◽  
Cell Responses ◽  
Rapid Spread

SummaryThe unprecedented and rapid spread of SARS-CoV-2 has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19 vaccinated nonhuman primate seroconverted rapidly and exhibited detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they did not develop fever and reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2 in human clinical trials.

scholarly journals A Combination Adjuvant for the Induction of Potent Antiviral Immune Responses for a Recombinant SARS-CoV-2 Protein Vaccine

2021 ◽  
Vol 12 ◽  
Author(s):  
Sonia Jangra ◽  
Jeffrey J. Landers ◽  
Raveen Rathnasinghe ◽  
Jessica J. O’Konek ◽  
Katarzyna W. Janczak ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibody ◽  
Cellular Responses ◽  
Cross Protection ◽  
Protein Vaccine ◽  
Mucosal Vaccination ◽  
Adaptive Immune ◽  
Antibody Titers ◽  
High Virus

Several SARS-CoV-2 vaccines have received EUAs, but many issues remain unresolved, including duration of conferred immunity and breadth of cross-protection. Adjuvants that enhance and shape adaptive immune responses that confer broad protection against SARS-CoV-2 variants will be pivotal for long-term protection as drift variants continue to emerge. We developed an intranasal, rationally designed adjuvant integrating a nanoemulsion (NE) that activates TLRs and NLRP3 with an RNA agonist of RIG-I (IVT DI). The combination adjuvant with spike protein antigen elicited robust responses to SARS-CoV-2 in mice, with markedly enhanced TH1-biased cellular responses and high virus-neutralizing antibody titers towards both homologous SARS-CoV-2 and a variant harboring the N501Y mutation shared by B1.1.7, B.1.351 and P.1 variants. Furthermore, passive transfer of vaccination-induced antibodies protected naive mice against heterologous viral challenge. NE/IVT DI enables mucosal vaccination, and has the potential to improve the immune profile of a variety of SARS-CoV-2 vaccine candidates to provide effective cross-protection against future drift variants.

Neutralizing antibody titers six months after Comirnaty vaccination: kinetics and comparison with SARS-CoV-2 immunoassays

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Andrea Padoan ◽  
Chiara Cosma ◽  
Francesco Bonfante ◽  
Foscarina della Rocca ◽  
Francesco Barbaro ◽  
...  
Keyword(s):  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
University Hospital ◽  
Serum Samples ◽  
Viral Neutralization ◽  
Previous Infection ◽  
Antibody Titers ◽  
Males And Females ◽  
Antibody Levels

Abstract Objectives mRNA vaccines, including Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer), elicit high IgG and neutralizing antibody (NAb) responses after the second dose, but the progressive decrease in serum antibodies against SARS-CoV-2 following vaccination have raised questions concerning long-term immunity, decreased antibody levels being associated with breakthrough infections after vaccination, prompting the consideration of booster doses. Methods A total number of 189 Padua University-Hospital healthcare workers (HCW) who had received a second vaccine dose were asked to collect serum samples for determining Ab at 12 (t12) and 28 (t28) days, and 6 months (t6m) after their first Comirnaty/BNT162b2 inoculation. Ab titers were measured with plaque reduction neutralization test (PRNT), and three chemiluminescent immunoassays, targeting the receptor binding domain (RBD), the trimeric Spike protein (trimeric-S), and surrogate viral neutralization tests (sVNT). Results The median percentages (interquartile range) for decrease in antibodies values 6 months after the first dose were 86.8% (67.1–92.8%) for S-RBD IgG, 82% (58.6–89.3%) for trimeric-S, 70.4% (34.5–86.4%) for VNT-Nab, 75% (50–87.5%) for PRNT50 and 75% (50–93.7%) for PRNT90. At 6 months, neither PRNT titers nor VNT-Nab and S-RBD IgG bAb levels correlated with age (p=0.078) or gender (p=0.938), while they were correlated with previous infection (p<0.001). Conclusions After 6 months, a method-independent reduction of around 90% in anti-SARS-CoV-2 antibodies was detected, while no significant differences were found between values of males and females aged between 24 and 65 years without compromised health status. Further efforts to improve analytical harmonization and standardization are needed.

Colour - mass balances and colour - dissolved organic carbon relationships in lakes and streams in central Ontario

1997 ◽  
Vol 54 (12) ◽  
pp. 2789-2795 ◽  
Author(s):  
Lewis A Molot ◽  
Peter J Dillon
Keyword(s):  
Organic Carbon ◽  
Dissolved Organic Carbon ◽  
Upper Bound ◽  
Balance Model ◽  
Strongly Correlated ◽  
Mass Balances ◽  
Loss Coefficients ◽  
The Mean ◽  
Study Sites

Colour and dissolved organic carbon (DOC) concentrations and mass balances were measured for seven unproductive lakes and 20 tributary streams between June 1980 and May 1992. Individual observations of colour, which measures an unknown DOC fraction assumed to be principally humic, were not good predictors of discrete DOC concentrations for any of the study sites. Long-term mean colour was, however, strongly correlated with long-term mean DOC concentrations in streams and lakes. Colour behaved differently from the total DOC pool in lakes. Lake retention and loss coefficients for colour were always higher than corresponding values for the total DOC pool, and the mean annual colour/DOC ratios in lake outflows were always less than the corresponding ratios in lake inputs, indicating that the coloured fraction was preferentially removed or photooxidized. A steady-state mass balance model was used to estimate the upper bound for the average coloured fraction of DOC in each lake. The upper bound for the seven lakes ranged from 34 to 88%, increasing with increasing colour, DOC, and total phosphorus.

scholarly journals Needle-Free Skin Patch Vaccination Method for Anthrax

2004 ◽  
Vol 72 (2) ◽  
pp. 1181-1183 ◽  
Author(s):  
Gary R. Matyas ◽  
Arthur M. Friedlander ◽  
Gregory M. Glenn ◽  
Stephen Little ◽  
Jianmei Yu ◽  
...  
Keyword(s):  
Protective Antigen ◽  
Neutralizing Antibody ◽  
Adjuvant Activity ◽  
Skin Patch ◽  
Transcutaneous Immunization ◽  
Antibody Titers ◽  
Recombinant Protective Antigen

ABSTRACT Three immunizations of mice with recombinant protective antigen (rPA) by transcutaneous immunization (TCI) induced long-term neutralizing antibody titers that were superior to those obtained with aluminum-adsorbed rPA. In addition, rPA alone exhibited adjuvant activity for TCI. Forty-six weeks after completion of TCI, 100% protection was observed against lethal anthrax challenge.

scholarly journals Redefining Non-Inferiority in Anamnestic Antibody Responses Using the Mean Increase of Log-Transformed Antibody Titers after Revaccination: Secondary Analysis of a Randomized Controlled Rabies Vaccination Trial

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 721
Author(s):  
Lisanne A. Overduin ◽  
Patrick H. P. Soentjens ◽  
Jelle J. Goeman ◽  
Magdalena A. Berkowska ◽  
Jacques J. M. van Dongen ◽  
...  
Keyword(s):  
Antibody Response ◽  
Controlled Trial ◽  
Secondary Analysis ◽  
Neutralizing Antibody ◽  
Primary Vaccination ◽  
Vaccination Schedule ◽  
Randomized Controlled ◽  
Antibody Titers ◽  
The Mean ◽  
The Difference

Non-inferiority in the anamnestic antibody response is conventionally determined by comparing seroconversion rates after revaccination. However, this approach is inadequate in the case of high pre-booster antibody titers. Therefore, we propose an alternative method to determine non-inferiority of booster responses. We used anonymized data from a randomized controlled trial (NCT01388985; EudraCT 2011-001612-62) in 500 adults, comparing a two-visit primary vaccination schedule (two intradermal 0.1 mL rabies vaccine doses on day 0 and 7) with a three-visit schedule (single intradermal 0.1 mL dose on day 0, 7, and 28). Participants were revaccinated intradermally (single dose) 1 to 3 years later. Rabies virus neutralizing antibody titers were measured on day 0 and 7 after revaccination. After log3-transformation of antibody titers, the mean increase in titers after revaccination was compared between schedules. Non-inferiority was defined as the lower bound of the two-sided 95% confidence interval not exceeding −0.369. Four hundred and ten participants fulfilled the inclusion criteria. The mean increase in log3 titer was 2.21 and 2.31 for the two-visit and three-visit schedule, respectively. The difference between these increases was −0.10 [−0.28, 0.08], meeting the non-inferiority criterion. In conclusion, comparing mean increases in log-transformed titers after revaccination appears to be a feasible and more informative method of studying non-inferiority regarding the anamnestic antibody response.

scholarly journals Immune cell phenotypes associated with disease severity and long-term neutralizing antibody titers after natural dengue virus infection

2021 ◽  
Vol 2 (5) ◽  
pp. 100278
Author(s):  
Angeline Rouers ◽  
Melissa Hui Yen Chng ◽  
Bernett Lee ◽  
Menaka P. Rajapakse ◽  
Kaval Kaur ◽  
...  
Keyword(s):  
Virus Infection ◽  
Dengue Virus ◽  
Disease Severity ◽  
Immune Cell ◽  
Neutralizing Antibody ◽  
Dengue Virus Infection ◽  
Antibody Titers ◽  
Cell Phenotypes
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