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Vaccines are highly effective at preventing severe coronavirus disease (COVID-19). With mRNA vaccines, further research is needed to understand the association between immunogenicity and reactogenicity, which is defined as the physical manifestation of an inflammatory response to a vaccination. This study analyzed the immune response and reactogenicity in humans, post immunization, to the former SARS-CoV-2 mRNA investigational vaccine CVnCoV (CV-NCOV-001 and CV-NCOV-002 clinical trials). Immunogenicity was investigated using whole-blood RNA sequencing, serum cytokine levels, and SARS-CoV-2-specific antibodies. The T cell responses in peripheral blood were assessed using intracellular cytokine staining (ICS) and high-dimensional profiling in conjunction with SARS-CoV-2 antigen-specificity testing via mass cytometry. Reactogenicity was graded after participants' first and second doses of CVnCoV using vaccine-related solicited adverse events (AEs). Finally, a Spearman correlation was performed between reactogenicity, humoral immunity, and serum cytokine levels to assess the relationship between reactogenicity and immunogenicity post CVnCoV vaccination. Our findings showed that the gene sets related to innate and inflammatory immune responses were upregulated one day post CVnCoV vaccination, while the gene sets related to adaptive immunity were upregulated predominantly one week after the second dose. The serum levels of IFNα, IFNγ, IP-10, CXCL11, IL-10, and MCP-1 increased transiently, peaking one day post vaccination. CD4+ T cells were induced in all vaccinated participants and low frequencies of CD8+ T cells were detected by ex vivo ICS. Using mass cytometry, SARS-CoV-2 spike-specific CD8+ T cells were induced and were characterized as having an activated effector memory phenotype. Overall, the results demonstrated a positive correlation between vaccine-induced systemic cytokines, reactogenicity, and adaptive immunity, highlighting the importance of the balance between the induction of innate immunity to achieve vaccine efficacy and ensuring low reactogenicity. [ABSTRACT FROM AUTHOR]

Background DNA plasmids promise a pragmatic alternative to viral vectors for prime-boost HIV-1 vaccines. We evaluated DNA plasmid versus canarypox virus (ALVAC) primes in 2 randomized, double-blind, placebo-controlled trials in southern Africa with harmonized trial designs. HIV Vaccine Trials Network (HVTN) 111 tested DNA plasmid prime by needle or needleless injection device (Biojector) and DNA plasmid plus gp120 protein plus MF59 adjuvant boost. HVTN 100 tested ALVAC prime and ALVAC plus gp120 protein plus MF59 adjuvant boost (same protein/adjuvant as HVTN 111) by needle. Methods and findings The primary endpoints for this analysis were binding antibody (bAb) responses to HIV antigens (gp120 from strains ZM96, 1086, and TV1; variable 1 and 2 [V1V2] regions of gp120 from strains TV1, 1086, and B.CaseA, as 1086 V1V2 and B.CaseA were correlates of risk in the RV144 efficacy trial), neutralizing antibody (nAb) responses to pseudoviruses TV1c8.2 and MW925.26, and cellular responses to vaccine-matched antigens (envelope [Env] from strains ZM96, 1086, and TV1; and Gag from strains LAI and ZM96) at month 6.5, two weeks after the fourth vaccination. Per-protocol cohorts included vaccine recipients from HVTN 100 (n = 186, 60% male, median age 23 years) enrolled between February 9, 2015, and May 26, 2015 and from HVTN 111 (n = 56, 48% male, median age 24 years) enrolled between June 21, 2016, and July 13, 2017. IgG bAb response rates were 100% to 3 Env gp120 antigens in both trials. Response rates to V1V2 were lower and similar in both trials except to vaccine-matched 1086 V1V2, with rates significantly higher for the DNA-primed regimen than the ALVAC-primed regimen: 96.6% versus 72.7% (difference = 23.9%, 95% CI 15.6%-32.2%, p < 0.001). Among positive responders, bAb net mean fluorescence intensity (MFI) was significantly higher with the DNA-primed regimen than ALVAC-primed for 1086 V1V2 (geometric mean [GM] 2,833.3 versus 1,200.9; ratio = 2.36, 95% CI 1.42-3.92, p 98% in both trials, with significantly higher 50% inhibitory dilution (ID.sub.50) among DNA-primed positive responders (n = 53) versus ALVAC-primed (n = 182) to tier 1A MW965.26 (GM 577.7 versus 265.7, ratio = 2.17, 95% CI 1.67-2.83, p < 0.001) and to TV1c8.2 (GM 187.3 versus 100.4, ratio = 1.87, 95% CI 1.48-2.35, p < 0.001). CD4+ T-cell response rates were significantly higher with DNA plasmid prime via Biojector than ALVAC prime (91.4% versus 52.8%, difference = 38.6%, 95% CI 20.5%-56.6%, p < 0.001 for ZM96.C; 88.0% versus 43.1%, difference = 44.9%, 95% CI 26.7%-63.1%, p < 0.001 for 1086.C; 55.5% versus 2.2%, difference = 53.3%, 95% CI 23.9%-82.7%, p < 0.001 for Gag LAI/ZM96). The study's main limitations include the nonrandomized comparison of vaccines from 2 different trials, the lack of data on immune responses to other non-vaccine-matched antigens, and the uncertain clinical significance of the observed immunological effects. Conclusions In this study, we found that further investigation of DNA/protein regimens is warranted given enhanced immunogenicity to the V1V2 correlates of decreased HIV-1 acquisition risk identified in RV144, the only HIV vaccine trial to date to show any efficacy., Author(s): Zoe Moodie 1,*, Stephen R. Walsh 2,3,4, Fatima Laher 5, Lucas Maganga 6, Michael E. Herce 7, Sarita Naidoo 8, Mina C. Hosseinipour 9, Craig Innes 10, Linda-Gail Bekker [...]

Background: Developing a cross-clade, globally effective HIV vaccine remains crucial for eliminating HIV.Methods: This placebo-controlled, double-blind, phase 1/2a study (NCT02935686) enrolled healthy HIV-uninfected adults at low risk for HIV infection. They were randomized (1:4:1) to receive 4 doses of an adenovirus 26-based HIV-1 vaccine encoding 2 mosaic Gag and Pol, and 2 mosaic Env proteins plus adjuvanted clade C gp140 (referred to here as clade C regimen), bivalent protein regimen (clade C regimen plus mosaic gp140), or placebo. Primary endpoints were safety and antibody responses.Results: 152/155 participants (clade C [n = 26], bivalent protein [n = 103], placebo [n = 26]) received ≥1 injection. The highest adverse event (AE) severity was grade 3 (local pain/tenderness: 12%, 2%, and 0% of the respective groups; solicited systemic AEs: 19%, 15%, 0%). HIV-1 mosaic gp140-binding antibody titers were 79,595 ELISA units [EU]/mL and 137,520 EU/mL in the clade C and bivalent protein groups (P < .001) post-dose 4 and 16,862 EU/mL and 25,162 EU/mL 6 months later. Antibody response breadth against clade C gp140 and clade C/non-clade C gp120 was highest in the bivalent protein group.Conclusions: Adding mosaic gp140 to the clade C regimen increased and broadened the elicited immune response without compromising safety or clade C responses. [ABSTRACT FROM AUTHOR]

Summary: Background: We used the RNActive® technology platform (CureVac N.V., Tübingen, Germany) to prepare CVnCoV, a COVID-19 vaccine containing sequence-optimized mRNA coding for a stabilized form of SARS-CoV‑2 spike (S) protein encapsulated in lipid nanoparticles (LNP). Methods: This is an interim analysis of a dosage escalation phase 1 study in healthy 18–60-year-old volunteers in Hannover, Munich and Tübingen, Germany, and Ghent, Belgium. After giving 2 intramuscular doses of CVnCoV or placebo 28 days apart we assessed solicited local and systemic adverse events (AE) for 7 days and unsolicited AEs for 28 days after each vaccination. Immunogenicity was measured as enzyme-linked immunosorbent assay (ELISA) IgG antibodies to SARS-CoV‑2 S‑protein and receptor binding domain (RBD), and SARS-CoV‑2 neutralizing titers (MN50). Results: In 245 volunteers who received 2 CVnCoV vaccinations (2 μg, n = 47, 4 μg, n = 48, 6 μg, n = 46, 8 μg, n = 44, 12 μg, n = 28) or placebo (n = 32) there were no vaccine-related serious AEs. Dosage-dependent increases in frequency and severity of solicited systemic AEs, and to a lesser extent local AEs, were mainly mild or moderate and transient in duration. Dosage-dependent increases in IgG antibodies to S‑protein and RBD and MN50 were evident in all groups 2 weeks after the second dose when 100% (23/23) seroconverted to S‑protein or RBD, and 83% (19/23) seroconverted for MN50 in the 12 μg group. Responses to 12 μg were comparable to those observed in convalescent sera from known COVID-19 patients. Conclusion: In this study 2 CVnCoV doses were safe, with acceptable reactogenicity and 12 μg dosages elicited levels of immune responses that overlapped those observed in convalescent sera. [ABSTRACT FROM AUTHOR]

Objective: To develop an anthropomorphic, deformable and multimodal pelvis phantom with positron emission tomography extension for radiotherapy (ADAM PETer). Methods: The design of ADAM PETer was based on our previous pelvis phantom (ADAM) and extended for compatibility with PET and use in 3T magnetic resonance imaging (MRI). The formerly manually manufactured silicon organ surrogates were replaced by three‐dimensional (3D) printed organ shells. Two intraprostatic lesions, four iliac lymph node metastases and two pelvic bone metastases were added to simulate prostate cancer as multifocal and metastatic disease. Radiological properties [computed tomography (CT) and 3T MRI] of cortical bone, bone marrow and adipose tissue were simulated by heavy gypsum, a mixture of Vaseline and K2HPO4 and peanut oil, respectively. For soft tissues, agarose gels with varying concentrations of agarose, gadolinium (Gd) and sodium fluoride (NaF) were developed. The agarose gels were doped with patient‐specific activity concentrations of a Fluorine‐18 labelled compound and then filled into the 3D printed organ shells of prostate lesions, lymph node and bone metastases. The phantom was imaged at a dual energy CT and a 3T PET/MRI scanner. Results: The compositions of the soft tissue surrogates are the following (given as mass fractions of agarose[w%]/NaF[w%]/Gd[w%]): Muscle (4/1/0.027), prostate (1.35/4.2/0.011), prostate lesions (2.25/4.2/0.0085), lymph node and bone metastases (1.4/4.2/0.025). In all imaging modalities, the phantom simulates human contrast. Intraprostatic lesions appear hypointense as compared to the surrounding normal prostate tissue in T2‐weighted MRI. The PET signal of all tumors can be localized as focal spots at their respective site. Activity concentrations of 12.0 kBq/mL (prostate lesion), 12.4 kBq/mL (lymph nodes) and 39.5 kBq/mL (bone metastases) were measured. Conclusion: The ADAM PETer pelvis phantom can be used as multimodal, anthropomorphic model for CT, 3T‐MRI and PET measurements. It will be central to simulate and optimize the technical workflow for the integration of PET/MRI‐based radiation treatment planning of prostate cancer patients. [ABSTRACT FROM AUTHOR]

Background The Pox-Protein Public-Private Partnership is performing a suite of trials to evaluate the bivalent subtype C envelope protein (TV1.C and 1086.C glycoprotein 120) vaccine in the context of different adjuvants and priming agents for human immunodeficiency virus (HIV) type 1 (HIV-1) prevention. Methods In the HIV Vaccine Trials Network 111 trial, we compared the safety and immunogenicity of DNA prime followed by DNA/protein boost with DNA/protein coadministration injected intramuscularly via either needle/syringe or a needle-free injection device (Biojector). One hundred thirty-two healthy, HIV-1–uninfected adults were enrolled from Zambia, South Africa, and Tanzania and were randomized to 1 of 6 arms: DNA prime, protein boost by needle/syringe; DNA and protein coadministration by needle/syringe; placebo by needle/syringe; DNA prime, protein boost with DNA given by Biojector; DNA and protein coadministration with DNA given by Biojector; and placebo by Biojector. Results All vaccinations were safe and well tolerated. DNA and protein coadministration was associated with increased HIV-1 V1/V2 antibody response rate, a known correlate of decreased HIV-1 infection risk. DNA administration by Biojector elicited significantly higher CD4+ T-cell response rates to HIV envelope protein than administration by needle/syringe in the prime/boost regimen (85.7% vs 55.6%; P =.02), but not in the coadministration regimen (43.3% vs 48.3%; P =.61). Conclusions Both the prime/boost and coadministration regimens are safe and may be promising for advancement into efficacy trials depending on whether cellular or humoral responses are desired. Clinical Trials Registration South African National Clinical Trials Registry (application 3947; Department of Health [DoH] no. DOH-27–0715–4917) and ClinicalTrials.gov (NCT02997969). [ABSTRACT FROM AUTHOR]

Background: We evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique. Methods: Healthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo. Results: Vaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, p<0.001) and subtype C gp140 (24300 versus 2700, p<0.001) Env protein. At relatively low titers, neutralizing antibody responses using the TZM-bl assay were more frequent in vaccinees given adjuvanted protein boost. Conclusion: Intradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significantly enhanced antibody responses. [ABSTRACT FROM AUTHOR]

Objectives: Combined positron emission tomography (PET) and magnetic resonance imaging (MRI) targeting the prostate-specific membrane antigen (PSMA) with a 68Ga-labelled PSMA-analog (68Ga-PSMA-11) is discussed as a promising diagnostic method for patients with suspicion or history of prostate cancer. One potential drawback of this method are severe photopenic (halo-) artifacts surrounding the bladder and the kidneys in the scatter-corrected PET images, which have been reported to occur frequently in clinical practice. The goal of this work was to investigate the occurrence and impact of these artifacts and, secondly, to evaluate variants of the standard scatter correction method with regard to halo-artifact suppression. Methods: Experiments using a dedicated pelvis phantom were conducted to investigate whether the halo-artifact is modality-, tracer-, and/or concentration-dependent. Furthermore, 31 patients with history of prostate cancer were selected from an ongoing 68Ga-PSMA-11-PET/MRI study. For each patient, PET raw data were reconstructed employing six different variants of PET scatter correction: absolute scatter scaling, relative scatter scaling, and relative scatter scaling combined with prompt gamma correction, each of which was combined with a maximum scatter fraction (MaxSF) of MaxSF = 75% or MaxSF = 40%. Evaluation of the reconstructed images with regard to halo-artifact suppression was performed both quantitatively using statistical analysis and qualitatively by two independent readers. Results: The phantom experiments did not reveal any modality-dependency (PET/MRI vs. PET/CT) or tracer-dependency (68Ga vs. 18F-FDG). Patient- and phantom-based data indicated that halo-artifacts derive from high organ-to-background activity ratios (OBR) between bladder/kidneys and surrounding soft tissue, with a positive correlation between OBR and halo size. Comparing different variants of scatter correction, reducing the maximum scatter fraction from the default value MaxSF = 75% to MaxSF = 40% was found to efficiently suppress halo-artifacts in both phantom and patient data. In 1 of 31 patients, reducing the maximum scatter fraction provided new PET-based information changing the patient’s diagnosis. Conclusion: Halo-artifacts are particularly observed for 68Ga-PSMA-11-PET/MRI due to 1) the biodistribution of the PSMA-11-tracer resulting in large OBRs for bladder and kidneys and 2) inaccurate scatter correction methods currently used in clinical routine, which tend to overestimate the scatter contribution. If not compensated for, 68Ga-PSMA-11 uptake pathologies may be masked by halo-artifacts leading to false-negative diagnoses. Reducing the maximum scatter fraction was found to efficiently suppress halo-artifacts. [ABSTRACT FROM AUTHOR]

HIV type 1 (HIV-1) remains a global health concern, with the greatest burden in sub-Saharan Africa. Despite 40 years of research, no vaccine candidate has shown durable and protective efficacy against HIV-1 acquisition. Although pre-exposure prophylaxis in groups with high vulnerability can be very effective, barriers to its use, such as perceived low acquisition risk, fear of stigma, and concerns about side-effects, remain. Thus, a population-based approach, such as an HIV-1 vaccine, is needed. The current study aimed to evaluate the efficacy and safety of a heterologous HIV-1 vaccine regimen, consisting of a tetravalent mosaic adenovirus 26-based vaccine (Ad26.Mos4.HIV) and aluminium phosphate-adjuvanted clade C glycoprotein (gp) 140, in young women at risk of acquiring HIV-1 in southern Africa. This randomised, double-blind, phase 2b study enrolled sexually active women without HIV-1 or HIV-2 aged 18–35 years at 23 clinical research sites in Malawi, Mozambique, South Africa, Zambia, and Zimbabwe. Participants were centrally randomly assigned (1:1) to receive intramuscular injections of vaccine or saline placebo in stratified permuted blocks via an interactive web response system. Study participants, study site personnel (except those with primary responsibility for study vaccine preparation and dispensing), and investigators were masked to treatment group allocation. The vaccine regimen consisted of Ad26.Mos4.HIV administered at months 0 and 3 followed by Ad26.Mos4.HIV administered concurrently with aluminium phosphate-adjuvanted clade C gp140 at months 6 and 12. The primary efficacy outcome was vaccine efficacy in preventing laboratory-confirmed HIV-1 acquisition diagnosed between visits at month 7 and month 24 after the first vaccination (VE[7–24]) in the per-protocol population, which included participants who had not acquired HIV-1 4 weeks after the third vaccination, received all planned vaccinations at the first three vaccination visits within the protocol-specified windows, and had no major protocol deviations that could affect vaccine efficacy. Primary safety outcomes were assessed in randomly assigned participants who received one study injection or more based on the actual injection received. The primary safety endpoints were the incidences of unsolicited adverse events (AEs), solicited local and systemic AEs, serious AEs, AEs of special interest, and AEs leading to discontinuation of vaccination. This trial is registered with ClinicalTrials.gov , NCT03060629 , and is complete. Between Nov 3, 2017, and June 30, 2019, 2654 women were randomly assigned, of whom 2636 women (median age of 23 years [IQR 20–25]) were enrolled and received at least one study injection (1313 assigned vaccine, 1323 placebo; 1317 received vaccine, 1319 placebo). Analysis of the primary efficacy outcome in the per-protocol cohort included 1080 women in the vaccine group and 1108 women in the placebo group; the incidence of HIV-1 acquisition per 100 person-years over months 7–24 after the first vaccination was 3·38 (95% CI 2·54–4·41) in the vaccine group and 3·94 (3·04–5·03) in the placebo group, with an estimated VE(7–24) of 14·10% (95% CI –22·00 to 39·51; p=0·40). There were no serious unsolicited AEs, AEs of special interest, or deaths related to the study vaccine. In the vaccine group, 663 (50·3%) of 1317 participants had grade 1 or 2 solicited local AEs and ten (0·8%) of 1317 participants had grade 3 or 4 solicited local AEs. In the placebo group, 305 (23·1%) of 1319 participants had grade 1 or 2 solicited local AEs and three (0·2%) of 1319 participants had grade 3 or 4 solicited local AEs. 863 (65·5%) of 1317 participants in the vaccine group had grade 1 or 2 solicited systemic AEs and 34 (2·6%) of 1317 participants had grade 3 or 4 solicited systemic AEs. 763 (57·8%) of 1319 participants in the placebo group had grade 1 or 2 solicited systemic AEs and 20 (1·5%) of 1319 participants had grade 3 or 4 solicited systemic AEs. Overall, three (0·2%) of 1317 participants in the vaccine group and three (0·2%) of 1319 participants in the placebo group discontinued vaccination due to an unsolicited AE, and three (0·2%) of 1317 participants in the vaccine group and one (0·1%) of 1319 participants in the placebo group discontinued vaccination due to a solicited AE. The heterologous Ad26.Mos4.HIV and clade C gp140 vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition in a population of young women in southern Africa at risk of HIV-1. Division of AIDS at the National Institute of Allergy and Infectious Diseases through the HIV Vaccine Trials Network, Bill & Melinda Gates Foundation, Janssen Vaccines & Prevention, US Army Medical Materiel Development Activity, and Ragon Institute. [ABSTRACT FROM AUTHOR]

Background: An effective vaccine is required to end the HIV pandemic. We evaluated the safety and immunogenicity of a DNA (DNA-HIV-PT123) vaccine with low- or high-dose bivalent (TV1.C and 1086.C glycoprotein 120) subtype C envelope protein combinations, adjuvanted with MF59 or AS01B., Methods: HIV Vaccine Trials Network (HVTN)108 was a randomized, placebo-controlled, double-blind, phase 1/2a trial conducted in the United States and South Africa. HIV-negative adults were randomly assigned to 1 of 7 intervention arms or placebo to assess DNA prime with DNA/protein/adjuvant boosts, DNA/protein/adjuvant co-administration, and low-dose protein/adjuvant regimens. HVTN111 trial participants who received an identical regimen were also included. Outcomes included safety and immunogenicity 2 weeks and 6 months after final vaccination., Results: From June 2016 to July 2018, 400 participants were enrolled (N = 334 HVTN108, N = 66 HVTN111); 370 received vaccine and 30 received placebo. There were 48 grade 3 and 3 grade 4 reactogenicity events among 39/400 (9.8%) participants, and 32 mild/moderate-related adverse events in 23/400 (5.8%) participants. All intervention groups demonstrated high IgG response rates (>89%) and high magnitudes to HIV-1 Env gp120 and gp140 proteins; response rates for AS01B-adjuvanted groups approached 100%. V1V2 IgG magnitude, Fc-mediated functions, IgG3 Env response rates, and CD4+ T-cell response magnitudes and rates were higher in the AS01B-adjuvanted groups. The AS01B-adjuvanted low-dose protein elicited greater IgG responses than the higher protein dose., Conclusions: The vaccine regimens were generally well tolerated. Co-administration of DNA with AS01B-adjuvanted bivalent Env gp120 elicited the strongest humoral responses; AS01B-adjuvanted regimens elicited stronger CD4+ T-cell responses, justifying further evaluation.ClinicalTrials.gov registration: NCT02915016, registered 26 September 2016., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

This phase 1, open-label, dose-escalation, multi-center study (NCT05477186) assessed the safety and immunogenicity of a booster dose of an mRNA COVID-19 vaccine (CV0501) encoding the SARS-CoV-2 Omicron BA.1 spike protein. Participants aged ≥ 18 years previously vaccinated with ≥ 2 doses of an mRNA COVID-19 vaccine received CV0501 doses ranging from 12 to 200 μg. After assessment of safety and immunogenicity of the 12 μg dose in 30 adults, 30 adults ≤ 64 years were randomized to receive either a 3 or 6 μg dose. Solicited adverse events (AEs) were collected for 7 days, unsolicited AEs for 28 days, and serious AEs (SAEs), medically attended AEs (MAAEs), and AEs of special interest (AESIs) until day (D) 181 post-vaccination. Serum neutralizing titers specific to SARS-CoV-2 BA.1, wild-type, Delta, and additional Omicron subvariants were assessed at D1, D15, D29, D91, and D181. Of 180 vaccinated participants (mean age: 49.3 years; 57.8% women), 70.6% had prior SARS-CoV-2 infection. Most solicited local (98.1%) and systemic (96.7%) AEs were of mild-to-moderate severity; the most common were injection site pain (57.5%; 33.3-73.3% across groups) and myalgia (36.9%; 13.3-56.7%). Unsolicited AEs were reported by 14.4% (6.7-26.7%) of participants (mild-to-moderate severity in 88.5% of the participants). Three participants (1.7%) reported SAEs, 16.7% (6.7-30.0%) reported MAAEs, and 8.3% (0.0-13.3%) reported AESIs (15 COVID-19 cases), none related to vaccination. Geometric means of serum neutralizing titers increased from baseline to D15 and D29 (dose-dependent), and then decreased over time. The safety and immunogenicity results supported advancement to a phase 2 trial.