Variant SARS-CoV-2 mRNA vaccines confer broad neutralization as primary or booster series in mice

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of a global pandemic that has led to more than 2.8 million deaths worldwide. Safe and effective vaccines are now available, including Moderna's COVID-19 vaccine (mRNA-1273) that showed 94% efficacy in prevention of symptomatic COVID-19 disease in a phase 3 clinical study. mRNA-1273 encodes for a prefusion stabilized full length spike (S) protein of the Wuhan-Hu-1 isolate. However, the emergence of SARS-CoV-2 variants has led to concerns of viral escape from vaccine-induced immunity. Several emerging variants have shown decreased susceptibility to neutralization by vaccine induced immunity, most notably the B.1.351 variant, although the overall impact on vaccine efficacy remains to be determined. Here, we present the initial evaluation in mice of two updated COVID-19 mRNA vaccines designed to target emerging SARS-CoV-2 variants: (1) monovalent mRNA-1273.351 encodes for the S protein found in the B.1.351 lineage and (2) mRNA-1273.211 comprising a 1:1 mix of mRNA-1273 and mRNA-1273.351. Both vaccines were evaluated as a 2-dose primary series in mice; mRNA-1273.351 was also evaluated as a booster dose in animals previously vaccinated with 2-doses of mRNA-1273. The results demonstrated that a primary vaccination series of mRNA-1273.351 was effective at increasing neutralizing antibody titers against the B.1.351 lineage, while mRNA-1273.211 was most effective at providing broad cross-variant neutralization in mice. In addition, these results demonstrated a third dose of mRNA-1273.351 significantly increased both wild-type and B.1.351-specific neutralization titers. Both mRNA-1273.351 and mRNA-1273.211 are currently being evaluated in additional pre-clinical challenge models and in phase 1/2 clinical studies.

Download Full-text

Heterologous SARS-CoV-2 Booster Vaccinations: Preliminary Report

10.1101/2021.10.10.21264827 ◽

2021 ◽

Author(s):

Robert L Atmar ◽

Kirsten E Lyke ◽

Meagan E Deming ◽

Lisa A Jackson ◽

Angela R Branche ◽

...

Keyword(s):

Phase 1 ◽

Booster Vaccination ◽

Neutralizing Antibody ◽

Open Label ◽

Vaccine Regimen ◽

Virus Particles ◽

Primary Series ◽

History Of ◽

Antibody Titers ◽

Binding Antibody

Background: While Coronavirus disease 2019 (Covid-19) vaccines are highly effective, breakthrough infections are occurring. Booster vaccinations have recently received emergency use authorization (EUA) for certain populations but are restricted to homologous mRNA vaccines. We evaluated homologous and heterologous booster vaccination in persons who had received an EUA Covid-19 vaccine regimen. Methods: In this phase 1/2 open-label clinical trial conducted at ten U.S. sites, adults who received one of three EUA Covid-19 vaccines at least 12 weeks prior to enrollment and had no reported history of SARS-CoV-2 infection received a booster injection with one of three vaccines (Moderna mRNA-1273 100-mcg, Janssen Ad26.COV2.S 5x1010 virus particles, or Pfizer-BioNTech BNT162b2 30-mcg; nine combinations). The primary outcomes were safety, reactogenicity, and humoral immunogenicity on study days 15 and 29. Results: 458 individuals were enrolled: 154 received mRNA-1273, 150 received Ad26.CoV2.S, and 154 received BNT162b2 booster vaccines. Reactogenicity was similar to that reported for the primary series. Injection site pain, malaise, headache, and myalgia occurred in more than half the participants. Booster vaccines increased the neutralizing activity against a D614G pseudovirus (4.2-76-fold) and binding antibody titers (4.6-56-fold) for all combinations; homologous boost increased neutralizing antibody titers 4.2-20-fold whereas heterologous boost increased titers 6.2-76-fold. Day 15 neutralizing and binding antibody titers varied by 28.7-fold and 20.9-fold, respectively, across the nine prime-boost combinations. Conclusion: Homologous and heterologous booster vaccinations were well-tolerated and immunogenic in adults who completed a primary Covid-19 vaccine regimen at least 12 weeks earlier.

Download Full-text

Navigating the Quagmire: Comparison and Interpretation of COVID-19 Vaccine Phase 1/2 Clinical Trials

Vaccines ◽

10.3390/vaccines8040746 ◽

2020 ◽

Vol 8 (4) ◽

pp. 746

Author(s):

Luca Tudor Giurgea ◽

Matthew James Memoli

Keyword(s):

Adverse Events ◽

Protective Efficacy ◽

Phase 1 ◽

Phase 3 ◽

Serious Adverse Events ◽

Safety Studies ◽

Antibody Titers ◽

Public Health Strategies

Vaccines against Coronavirus Disease 2019 Originated-19) have been developed with unprecedented rapidity, many utilizing novel strategies. As of November 2020, a series of publications have outlined the results of phase 1/2 studies of nine different vaccines planned to move forward to phase 3 trials. The results are encouraging, demonstrating a paucity of severe or serious adverse events and robust induction of antibody titers. Determination of the vaccine candidates with the highest protective efficacy and best adverse event profiles will be essential in refining public health strategies. However, differences in study design and reporting of data make comparisons of existing phase 1/2 studies difficult. With respect to safety, studies have variable follow-up times and may use different definitions for adverse events. Immunogenicity outcomes are even more inconsistent, with variations in timepoints and critical differences in the types of antibodies studied as well as methodological differences in assays. Furthermore, the correlates of protection in COVID-19 are not known. Harmonization of phase 3 trial designs and use of objective and meaningful clinical outcomes will be crucial in streamlining future global responses to the pandemic.

Download Full-text

Inference of SARS-CoV-2 spike-binding neutralizing antibody titers in sera from hospitalized COVID-19 patients by using commercial enzyme and chemiluminescent immunoassays

10.1101/2020.09.07.20188151 ◽

2020 ◽

Author(s):

Arantxa Valdivia ◽

Ignacio Torres ◽

Victor Latorre ◽

Carla Frances-Gomez ◽

Eliseo Albert ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Neutralization Assay ◽

Virus Neutralization ◽

Pseudotyped Virus ◽

S Protein ◽

Neutralizing Activity ◽

Virus Neutralization Assay ◽

Degree Correlation ◽

Antibody Titers

Background: Whether antibody levels measured by commercially-available enzyme or chemiluminescent immunoassays targeting the SARS-CoV-2 spike (S) protein can act as a proxy for serum neutralizing activity remains to be established for many of these assays. Objectives: To evaluate the degree of correlation between neutralizing antibodies (NtAb) binding the SARS-CoV-2 Spike (S) protein and SARS-CoV-2-S-IgG levels measured by four commercial immunoassays in sera drawn from hospitalized COVID-19 patients. Patients and Methods: Ninety sera from 51 hospitalized COVID-19 patients were assayed by a pseudotyped virus neutralization assay, the LIAISON SARS-CoV-2 S1/S2 IgG, the Euroimmun SARS-CoV-2 IgG ELISA, the MAGLUMI 2019-nCoV IgG and the COVID-19 ELISA IgG assays. Results: Overall, the results obtained with the COVID-19 ELISA IgG test showed the highest agreement with the NtAb assay (κ, 0.85; 95% CI, 0.63-1). The most sensitive tests were the pseudotyped virus NtAb assay and the COVID-19 ELISA IgG assay (92.2% for both). Overall, the degree correlation between antibody titers resulting in 50% virus neutralization (NtAb50) in the pseudotyped virus assay and SARS-CoV-2 IgG levels was strong for the Euroimmun SARS-CoV-2 IgG ELISA (Rho=0.73) and moderate for the remaining assays (Rho=0.48 to 0.59). The kinetic profile of serum NtAb50 titers could not be reliably predicted by any of the SARS-CoV-2 IgG immunoassays. Conclusions: the suitability of SARS-CoV-2-S-IgG commercial immunoassays for inferring neutralizing activity of sera from hospitalized COVID-19 patients varies widely across tests and is influenced by the time of sera collection after the onset of symptoms.

Download Full-text

Safety and immunogenicity trial of an inactivated SARS-CoV-2 vaccine-BBV152: a phase 1, double-blind, randomised control trial

10.1101/2020.12.11.20210419 ◽

2020 ◽

Author(s):

Raches Ella ◽

Krishna Mohan ◽

Harsh Jogdand ◽

Sai Prasad ◽

Siddharth Reddy ◽

...

Keyword(s):

Phase 1 ◽

Neutralizing Antibody ◽

Cold Chain ◽

Wild Type Virus ◽

Randomised Control Trial ◽

Enzyme Linked Immunosorbent Assay ◽

Double Blind ◽

Efficacy Trials ◽

National Immunization ◽

Antibody Titers

Background: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine formulated with a TLR 7/8 agonist molecule adsorbed to alum (Algel-IMDG). Methods We conducted a double-blind randomized controlled phase 1 clinical trial to evaluate the safety and immunogenicity of BBV152. A total of 375 participants were randomized equally to receive three vaccine formulations (n=100 each) prepared with 3 μg with Algel-IMDG, 6 μg with Algel-IMDG, and 6 μg with Algel, and an Algel only control arm (n=75). Vaccines were administered on a two-dose intramuscular accelerated schedule on day 0 (baseline) and day 14. The primary outcomes were reactogenicity and safety. The secondary outcomes were immunogenicity based on the anti-IgG S1 response (detected with an enzyme-linked immunosorbent assay [ELISA] and wild-type virus neutralization [microneutralization and plaque reduction neutralization assays]). Cell-mediated responses were also evaluated. Results: Reactogenicity was absent in the majority of participants, with mild events. The majority of adverse events were mild and were resolved. One serious adverse event was reported, which was found to be unrelated to vaccination. All three vaccine formulations resulted in robust immune responses comparable to a panel of convalescent serum. No significant differences were observed between the 3-μg and 6-μg Algel-IMDG groups. Neutralizing responses to homologous and heterologous SARS-CoV-2 strains were detected in all vaccinated individuals. Cell-mediated responses were biased to a Th-1 phenotype. Conclusions BBV152 induced binding and neutralising antibody responses and with the inclusion of the Algel-IMDG adjuvant, this is the first inactivated SARS-CoV-2 vaccine that has been reported to induce a Th1-biased response. Vaccine-induced neutralizing antibody titers were reported with two divergent SARS-CoV-2 strains. BBV152 is stored between 2°C and 8°C, which is compatible with all national immunization program cold chain requirements. Both Algel-IMDG formulations were selected for the phase 2 immunogenicity trials. Further efficacy trials are underway.

Download Full-text

Immunogenicity of a Live-Attenuated Dengue Vaccine Using a Heterologous Prime-Boost Strategy in a Phase 1 Randomized Clinical Trial

The Journal of Infectious Diseases ◽

10.1093/infdis/jiaa603 ◽

2020 ◽

Author(s):

Leyi Lin ◽

Michael A Koren ◽

Kristopher M Paolino ◽

Kenneth H Eckels ◽

Rafael De La Barrera ◽

...

Keyword(s):

Immune Responses ◽

Dengue Virus ◽

Phase 1 ◽

Vaccination Strategy ◽

Neutralizing Antibody ◽

Dengue Vaccine ◽

Serious Adverse Events ◽

Live Attenuated Vaccine ◽

Antibody Titers ◽

Global Health Problem

Abstract Background Dengue is a global health problem and the development of a tetravalent dengue vaccine with durable protection is a high priority. A heterologous prime-boost strategy has the advantage of eliciting immune responses through different mechanisms and therefore may be superior to homologous prime-boost strategies for generating durable tetravalent immunity. Methods In this phase 1 first-in-human heterologous prime-boost study, 80 volunteers were assigned to 4 groups and received a tetravalent dengue virus (DENV-1–4) purified inactivated vaccine (TDENV-PIV) with alum adjuvant and a tetravalent dengue virus (DENV-1–4) live attenuated vaccine (TDENV-LAV) in different orders and dosing schedules (28 or 180 days apart). Results All vaccination regimens had acceptable safety profiles and there were no vaccine-related serious adverse events. TDEN-PIV followed by TDEN-LAV induced higher neutralizing antibody titers and a higher rate of tetravalent seroconversions compared to TDEN-LAV followed by TDEN-PIV. Both TDEN-PIV followed by TDEN-LAV groups demonstrated 100% tetravalent seroconversion 28 days following the booster dose, which was maintained for most of these subjects through the day 180 measurement. Conclusions A heterologous prime-boost vaccination strategy for dengue merits additional evaluation for safety, immunogenicity, and potential for clinical benefit. Clinical Trials Registration NCT02239614.

Download Full-text

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 ◽

10.3390/vaccines8040721 ◽

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.

Download Full-text

Different Profiles of Antibodies and Cytokines Were Found Between Severe and Moderate COVID-19 Patients

Frontiers in Immunology ◽

10.3389/fimmu.2021.723585 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yaolin Guo ◽

Tianyi Li ◽

Xinyi Xia ◽

Bin Su ◽

Hanping Li ◽

...

Keyword(s):

Neutralizing Antibody ◽

Healthy Individuals ◽

S Protein ◽

Elisa System ◽

N Protein ◽

Tnf Α ◽

Significant Difference ◽

Positive Rate ◽

Antibody Titers ◽

Ifn Γ

ObjectivesOur objective was to determine the antibody and cytokine profiles in different COVID-19 patients.MethodsCOVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests.ResultsA total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody.ConclusionsOur findings show the severe COVID-19 patients’ antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.

Download Full-text

Receptor-binding domain recombinant protein RBD219-N1C1 on alum-CpG induces broad protection against SARS-CoV-2 variants of concern

10.1101/2021.07.06.451353 ◽

2021 ◽

Author(s):

Jeroen Pollet ◽

Ulrich Strych ◽

Wen-Hsiang Chen ◽

Leroy Versteeg ◽

Brian Keegan ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Vaccine Formulation ◽

Broadly Neutralizing Antibodies ◽

Phase 3 ◽

Advanced Phase ◽

Antibody Titers ◽

Cellular Immune

We conducted preclinical studies in mice using a yeast-produced SARS-CoV-2 RBD219-N1C1 subunit vaccine candidate formulated with aluminum hydroxide (alum) and CpG deoxynucleotides. This vaccine formulation is similar to one that entered advanced phase 3 clinical development in India. We compared the immune response of mice vaccinated with RBD219-N1C1/alum to mice vaccinated with RBD219-N1C1/alum+CpG. We also evaluated mice immunized with RBD219-N1C1/alum+CpG and boosted with RBD219-N1C1/alum. Mice were immunized twice intramuscularly at a 21-day interval. Compared to two doses of the RBD219-N1C1/alum formulation, the RBD219-N1C1/alum+CpG vaccine induced a stronger and more balanced Th1/Th2 cellular immune response, with high levels of neutralizing antibodies against the original Wuhan isolate of SARS-CoV-2 as well as the B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.1 (Kappa) variants. Notably, the sera from mice that received two 7 μg doses of RBD219-N1C1/alum+CpG showed more than 18 times higher neutralizing antibody titers against B.1.351, than the WHO International Standard for anti-SARS-CoV-2 immunoglobulin NIBSC 20/136. Interestingly, a booster dose did not require the addition of CpG to induce this effect. The data reported here reinforces that the RBD219-N1C1/alum+CpG vaccine formulation is suitable for inducing broadly neutralizing antibodies against SARS-CoV-2 including three variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa).

Download Full-text

Measles Vaccine Immunogenicity in 6- Versus 15-Month-Old Infants Born to Mothers in the Measles Vaccine Era

PEDIATRICS ◽

10.1542/peds.93.6.939 ◽

1994 ◽

Vol 93 (6) ◽

pp. 939-943

Author(s):

Candice E. Johnson ◽

Judy Whitwell ◽

Mary L. Kumar ◽

David R. Nalin ◽

Linda W. Chui ◽

...

Keyword(s):

Geometric Mean ◽

Primary Vaccination ◽

Maternal Serum ◽

Geometric Mean Titer ◽

Measles Vaccine ◽

Primary Immunization ◽

Antibody Assays ◽

History Of ◽

Antibody Titers ◽

Induced Immunity

Hypothesis. The low titer of measles antibody in infants of mothers with vaccine-induced immunity may allow immunization against measles before 15 months of age. Methods. Six- and 15-month-old infants born to mothers ≤ 30 years of age with no history of measles were recruited. Infants enrolled at 6 months of age were immunized with monovalent measles vaccine (Attenuvax), and maternal serum and infant pre- and postvaccination sera were obtained. Those enrolled for primary vaccination at 15 months of age received either Attenuvax (N = 12) or M-M-RII (N = 3). Six-month-old infants were revaccinated with M-M-RII at 15 months of age; pre- and postrevaccination sera were again obtained. Three antibody assays were used: a measles neutralizing assay (NT) and two enzyme immunoassays (EIA) for measles IgG and measles IgM. Results. Among primary vaccinees, 14 of 19 infants aged 6 months (74%) developed NT antibody, as did 15 of 15 infants aged 15 months (100%). The reciprocal geometric mean titer of 6-month-old seroresponders was 23.3, significantly lower than that of the 15-month-old primary vaccinees (87.7, P < .001). Primary seroconversion rates by EIA were 53% for 6-month-old infants and 100% for those aged 15 months. Revaccination of infants who had received Attenuvax at 6 months of age resulted in 100% NT positivity; the geometric mean titer rose to equal that of the group given primary immunization at 15 months of age. Measles IgM antibody was detected in 10 of 14 infants tested 1 month after primary vaccination at 15 months, but was not detected in any of the revaccinated infants after the second dose at 15 months of age (P < .001). Conclusions. 1) Immunization with measles vaccine in infants born to vaccine-immune mothers at 6 months of age induced NT antibody in 74% of infants. 2) Revaccination of prior 6-month-old vaccinees at 15 months resulted in antibody titers equivalent to 15-month-old vaccinees. 3) Lack of an IgM response following revaccination suggests that even seronegative infants may be primed to respond on re-exposure to measles.

Download Full-text

633. Preliminary Results from a Phase 1 Single Ascending-Dose Study Assessing Safety, Serum Viral Neutralizing Antibody Titers (sVNA), and Pharmacokinetic (PK) Profile of ADG20: an Extended Half-Life Monoclonal Antibody Being Developed for the Treatment and Prevention of Coronavirus Disease (COVID-19)

Open Forum Infectious Diseases ◽

10.1093/ofid/ofab466.831 ◽

2021 ◽

Vol 8 (Supplement_1) ◽

pp. S420-S420

Author(s):

Helen Paguntalan ◽

Zoltán Magyarics ◽

Lynn E Connolly ◽

Ellie Hershberger ◽

Kristin Narayan ◽

...

Keyword(s):

Monoclonal Antibody ◽

Half Life ◽

Phase 1 ◽

Neutralizing Antibody ◽

Post Dose ◽

Treatment And Prevention ◽

Dose Study ◽

Antibody Titers ◽

Single Ascending Dose Study ◽

Ongoing Phase

Abstract Background ADG20 is a fully human IgG1 monoclonal antibody engineered to have high potency and broad neutralization against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other SARS-like CoVs with pandemic potential by binding to a highly conserved epitope in the receptor-binding domain (RBD) of the spike protein. The Fc region of ADG20 has been modified to provide an extended half-life. ADG20 is in clinical development for the treatment and prevention of COVID-19. Methods This is an ongoing Phase 1, randomized, placebo (PBO)-controlled, single ascending-dose study of ADG20 administered intramuscularly (IM) or intravenously (IV) to healthy adults aged 18–50 years with no evidence of prior or current SARS-CoV-2 infection. Participants were randomized 8:2 in 3 cohorts (N=10/cohort: n=8 ADG20, n=2 PBO): ADG20 300 mg IM, 500 mg IV, and 600 mg IM. Safety, tolerability, PK, and sVNA titers were assessed up to 3 months post dose. Serum ADG20 concentrations were measured with a validated hybrid ligand binding liquid chromatography–mass spectrometry (MS)/MS assay. sVNA titers against authentic SARS-CoV-2 were determined by a plaque reduction neutralization assay. Results Overall, 30 participants received ADG20 (n=24) or PBO (n=6). Blinded safety data for all cohorts and PK/sVNA titer data for the 300 mg IM cohort are reported. Through a minimum of 10 weeks post dose, no study drug-related adverse events (AEs), serious AEs, injection site reactions, or hypersensitivity reactions were reported. The observed preliminary PK profile was dose proportional, consistent with an extended half-life monoclonal antibody, and well predicted by translational physiologically-based PK modeling. The measured 50% sVNA titer (MN50; geometric mean [coefficient of variation, %]) was 1382 (32.7%) 13 days after a single 300 mg IM dose. These values are within the range of peak serum neutralizing antibody titers reported for COVID-19 mRNA vaccines. Conclusion A single dose of ADG20, up to 600 mg IM, was well tolerated. Preliminary PK and sVNA titer profiles support the ongoing Phase 2/3 trials of ADG20 at a 300 mg IM dose for the prevention of COVID-19 (EVADE: NCT04859517) and treatment of ambulatory patients with mild to moderate COVID-19 (STAMP: NCT04805671). Disclosures Helen Paguntalan, MD, Adagio Therapeutics, Inc. (Scientific Research Study Investigator) Zoltán Magyarics, MD, PhD, Adagio Therapeutics, Inc. (Consultant) Lynn E. Connolly, MD, PhD, Adagio Therapeutics, Inc. (Employee) Ellie Hershberger, PharmD, Adagio Therapeutics, Inc. (Employee) Kristin Narayan, PhD, Adagio Therapeutics, Inc. (Employee) Deepali Gupta, BS, Adagio Therapeutics, Inc. (Employee) Paul G. Ambrose, PharmD, Adagio Therapeutics, Inc. (Employee) Frank Engler, PhD, Adagio Therapeutics, Inc. (Independent Contractor) Ed Campanaro, BSN, MSHS, Adagio Therapeutics, Inc. (Employee) Anita F. Das, PhD, Adagio Therapeutics, Inc. (Consultant) Pete Schmidt, MD, Adagio Therapeutics, Inc. (Employee)

Download Full-text