Table 1 Published and registered clinical trials of repRNA vaccines against infectious diseases
From: Replicon RNA vaccines: design, delivery, and immunogenicity in infectious diseases and cancer
Ref # Study ID number # Phase name of the vaccine | Viral vector | Delivery approach | Antigen | Vaccination dose regimen | Subjects | Toxicities | Tumor antigen-specific immune response |
|---|---|---|---|---|---|---|---|
255,256 PACTR201503001057193 Phase III rVSV-ZEBOV | VSV | Unknown | Surface glycoprotein of Zaire Ebolavirus | Dose level: 2 × 10⁷ PFU 1 injection IM | 8334 Immediately vaccinated: 3796. M: 2573, F:1223 Delayed/ not vaccinated: 4538. M: 2590, F: 1948 | 7211 mild adverse events: headache, fatigue, and muscle pain 80 serious adverse events: related: 1 febrile reaction, 1 anaphylaxis. Possibly related: 1 influenza-like illness. All have recovered without long-term complications | 100% vaccine efficacy |
258 NCT00439803 Phase I AVX601 | VEEV | VRP | CMV gB (Towne strain) and a pp65/IEI fusion protein | Dose levels: 1 × 107/1 × 108 IU per dose Doses at weeks 0, 8, 24 IM/ SC | 40 M: 15 F: 25 Caucasian: 34 Black: 6 Healthy volunteers who have not previously been infected with CMV | Only mild to moderate AEs were witnessed, which were dose-dependent Local reactogenicity events: erythema, swelling, injection site pain, tenderness Systemic reactogenicity events: myalgias, fatigue, malaise or headache, nausea, vomiting, fever | T cell and B cell |
259 NCT00063778 and NCT00097838 Phase I AVX101 | VEEV | VRP | The nonmyristoylated form of HIV gag | Dose levels: (1 × 104, 1 × 105, 1 × 106, 1 × 107, and 1 × 108 IU per 0.5 ml Doses at day 0, day 28, day 84 SC | 132 M: 72 F:60 White non-Hispanic: 47 Black/African American non-Hispanic: 75 Hispanic: 7 Native Hawaiian/Pacific Islander or multiracial: 3 Healthy individuals | 48.5% of subjects: mild local reactions 2.3% of subjects: moderate pain or tenderness at the injection site 59.1% of subjects: Systemic reactogenicity symptoms, mostly mild and were not treatment specific. No serious AEs related to the vaccination 3 subjects discontinued the vaccination due to AEs: recurrence of Bell’s palsy, low neutrophil count, and fatigue | Suboptimal cellular and humoral responses |
260 NCT04480957 phase I/II ARCT-021 | VEEV | proprietary 61 LUNAR® LNP | SARS-CoV-2 full-length spike protein | Phase 1: Younger adults: one-dose administration (dose levels 1.0 μg, 5.0 μg, 7.5 μg and 10 μg ARCT-021). Older adults: 7.5 μg ARCT-021, one dose Phase 2: Younger and older adults: two-dose administrations of 3.0 μg and 5.0 μg ARCT-021 with a 28 day-interval IM | 106 M: 78 F: 28 Asian: 100 White: 4 American Indian or Alaskan Native: 1 Other: 1 Healthy adults | Local reactions: injection site tenderness and pain, mainly grade 1,2. No grade 4 local reactions Systemic Reactions: fatigue, headache, myalgia, chills, and fever. Mainly grade 1/2, and no grade 4 events | T cell and B cell |
261 ISRCTN17072692, EudraCT 2020–001646-20 Phase I COVAC1 | VEEV | LNP | Spike (S) glycoprotein of SARS-CoV-2 stabilized in the pre-fusion conformation with two proline substitutions | Dose levels: 0.1 mg, 0.3 mg, 1.0 mg, 2.5 mg, 5.0 mg, 10.0 mg 2 injections 4 weeks apart IM | 192 M:119 F:73 White: 151 Mixed: 11 Asian or Asian British: 16 Other: 13 Not stated: 1 Healthy individuals | No serious adverse events related to vaccination Dose-dependent systemic reactions: fatigue, headache, myalgia, arthralgia, chill, and nausea Dose-dependent local reactions: tenderness/discomfort and pain, erythema, and swelling | B cell |
262 ISRCTN17072692, EudraCT 2020–001646-20 Phase IIa COVAC1 | VEEV | LNP | Spike (S) glycoprotein of SARS-CoV-2 stabilized in the pre-fusion conformation with two proline substitutions | First injection: 1.0 μg 14 weeks later, second injection: 10.0 μg | 222 M:114 F:108 SARS-CoV-2 naïve: 191 SARS-CoV-2 positive: 31 Age: 18–39: 64 40–59: 50 60–75: 74 | After the first vaccination: grade 1–2 injection site pain, tenderness/discomfort. Grade 1–2 chills/shivering, myalgia, arthralgia, fatigue and headache After the second vaccination: grade 1–3 injection site pain, tenderness/discomfort Grade 1–3 chills/shivering, myalgia, arthralgia, fatigue, headache, nausea and fever. Clinically insignificant Neutropaenia | B cell |
263 NCT04863131 Phase I/II EXG-5003 | VEEV | Naked RNA | RBD of SARS-CoV-2 spike protein | Cohort 1: 5 µg of EXG-5003 Cohort 2: 25 µg of EXG-5003 Doses on day 1 and day 29 after randomization ID | 40 M: 24 F: 16 Asian: 40 Healthy adults | Local AEs: grade 1 pain, redness, swelling Systemic AEs: grade 1 fever, headache, muscle pain. Grade 1/2 fatigue | T cell responses in cohort 2 subjects |
264 NCT00440362 Phase I/II AVX502 | Alphavirus | VRP | Influenza HA protein | One dose: 2 × 107 IU, 2 × 108 IU Two doses: 2 × 107 IU, 2 × 108 IU IM/SC | 216 Healthy volunteers | Unknown | Unknown |
265,266 NCT04844268, NCT05132907 Phase I HDT-301 | VEEV | LION | SARS-CoV-2 spike protein | Cohort 1: individuals vaccinated against COVID-19 and two-dose schedule of HDT-301 56 days apart Cohort 2: individuals who have been vaccinated against COVID-19 and a one-dose schedule of HDT-301 Cohort 3: individuals with no history of vaccination against COVID-19 who will receive a two-dose schedule of HDT-301 56 days apart | Healthy (vaccinated or unvaccinated) adult subjects | Unknown | Unknown |
267 NCT05876364 Phase I QTP104 | Unknown | LION | SARS-CoV-2 spike protein | 2 dose injections on days 1 and 28 Cohort 1: QTP104 1ug Cohort 2: QTP104 5ug Cohort 3: QTP104 25ug IM | Unknown | Unknown | Unknown |