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. 2022 Apr 11;35(6):e15461. doi: 10.1111/dth.15461

TABLE 3.

Mucocutaneous reaction after COVID‐19 vaccination reported in “RCTs” studies

Supplemental references a First author Phase of RCT Number of participants (n) Women percentage Mean of Age (year) Participants' comorbidity and (age group in study) Vaccine dose Days between doses Dose number Any symptoms after vaccine Percentage of mucocutaneous reaction Time of onset the reactions (days)
1. mRNA vaccines
1.1. BNT162b2 (n = 39,144)
1 Walsh, E. E. Phase 1 36 39 36.7 NM (18–55 years) 10, 20, and 30 μg 21 1 Injection site pain, fever, fatigue, chills, small numbers of severe systemic events (fatigue, headache, chills, muscle pain, and joint pain)

Injection site redness: (20 μg:0%, 30 μg:8%)

Injection site swelling (10 μg:17%)

 Peak at d2
2 Sahin, U. Phase 1/2 (extended) 12 66.7 34.8 NM 10 μg 21 1&2 Injection site pain, fever, chills, headache, fatigue, muscle pain, joint pain, diarrhea Injection site: swelling (8%)

0–7,

22–28
2 Sahin, U. Phase 1/2 (extended) 12 33.3 46.7 NM 30 μg 21 1&2 Injection site pain, chills, headache, fatigue, muscle pain, joint pain, diarrhea Injection site: swelling (58.3%),redness(8%)

0–7,

22–28
3 Polack Phase 2/3 18,860 48.9 51.2 Obesity (34.8%) 30 μg 21 1 Injection site pain, fever, fatigue, headache, chills, vomiting, diarrhea, muscle pain, jointpain, severe systemic events (<2%) Injection site: redness (16‐55 years:5%, ≥55 years: 5%), swelling (16‐55 years:6%, ≥55 years: 7%, lymphadenopathy (0.3%), NM
3 Polack Phase 2/3 18,556 48.9 51.2 Obesity (34.8%) 30 μg 21 2 Injection site pain, fever, fatigue, headache, chills, vomiting, diarrhea, muscle pain, jointpain, severe systemic events: <2% except for fatigue (3.8%) and headache (2.0%) Injection site: redness (16‐55 years:6%, ≥55 years: 7%), swelling (16‐55 years:6%, ≥55 years: 7%) NM
4 Frenck, R. W., Jr. Phase 3 1131 49.9 13.6 Baseline COVID +(4.1%) (12–15 years) 30 μg 21 1&2 Injection site pain, fatigue, headache, chills, vomiting, diarrhea, muscle pain, joint pain,fever Injection site: redness(1st:6%, 2nd:5%), swelling(1st:7%, 2nd:5%) 0–7
4 Frenck, R. W., Jr. Phase 3 537 52.5 19.4 Baseline COVID +(5.6%) (16–25 years) 30 μg 21 1&2 Injection site pain, fatigue, headache, chills, vomiting, diarrhea, muscle pain, joint pain,fever Injection site: redness(1st:6%, 2nd:6%), swelling(1st:8%, 2nd:7%) 0–7
1.2. BNT162b2 booster in ChAdOx1‐S‐primed participants (CombiVacS) (n = 450)
5 Borobia, A. M. Phase 2 450 57 43.93 Hypothyroidism, Allergies, Asthma, HTN, Hypercholesterolaemia, Psychiatric, Migraine, Insomnia, Arthralgia, Back pain, Drug hypersensitivity, baseline COVID + (0%)

30 μg

 50–84 2 Injection site pain and discomfort, malaise, pyrexia, headache, myalgia, arthralgia, chills, cough, nausea Injection site: erythema(31%), pruritus(10.9%), urticaria(15%), hardness(35.5%), pustule(0.2%), general pruritus (2%), rash (1.3%) (among 448 subjects) 0–7
1.3. BNT162b1 (n = 324)
6 Li, J. Phase 1 24 50 37.9 Cardiac Ischemia,Sinus Bradycardia,Hyperuricemia, Nasopharyngitis, Increasedblood uric acid,HTN (18–55 years) 10 μg 21 1&2 Injection site pain, fever, headache, fatigue, malaise, joint pain, muscle pain, chills, nausea, anorexia, diarrhea, Injection site: redness (1st:12.5%, 2nd:16.7%), swelling(1st: 12.5%, 2nd:8.3%) 0–7
6 Li, J. Phase 1 24 50 70.5 Hyperuricemia, HTN, DM (65–85 years) 10 μg 21 1&2 Injection site pain, fever, headache, fatigue, malaise, chills Injection site: redness (1st:12.5%) 0–7
6 Li, J. Phase 1 24 50 39.7 Sinus Bradycardia, Hyperuricemia, Blood uric acid increased (18–55 years) 30 μg 21 1&2 Injection site pain, fever, headache, fatigue, malaise, joint pain, muscle pain, chills, nausea, anorexia, diarrhea, vomiting Injection site: redness (1st:25% 2nd:20.9%), swelling(1st:20.8%, 2nd:16.7%), induration(1st:8.3%, 2nd:4.2%) 0–7
6 Li, J. Phase 1 24 50 68.5 Hyperuricemia, HTN, DM (65–85 years) 30 μg 21 1&2 Injection site pain, fever, headache, fatigue, malaise, joint pain, muscle pain, chills, anorexia Injection site: redness (1st: 16.6%),swelling(2nd: 21.7%), induration(1st: 4.2%) 0–7
1 Walsh, E. E. Phase 1 36 39 36.7 NM (18–55 years) 10 μg, 20 μg, 30 μg 21 1 Injection site pain, fever, fatigue, chills

Injection site redness: (30 μg:17%)

Injection site swelling: (10 μg:25%, 20 μg:17%)

 Peak at d2
1 Walsh, E. E. Phase 1 36 39 36.7 NM (18–55 years) 10 μg, 20 μg, 30 μg 21 2

Injection site pain, fever, fatigue, chills

*dose‐dependent (greater after the 2nd dose than after the 1st dose, both systemic and local reactions)

Injection site redness: (30 μg:17%)

Injection site swelling: (20 μg:8%, 30 μg:25%)

 Peak at d2
1 Walsh, E. E. Phase 1 36 67 70.1 NM (65–85 years) 10 μg, 20 μg, 30 μg 21 1 Injection site pain, fever, fatigue, chills (systemic events milder than in the younger participants) Injection site swelling: (10 μg:8%, 20 μg:8%, 30 μg:17%) Peak at d2
1 Walsh, E. E. Phase 1 36 67 70.1 NM (65–85 years) 10 μg, 20 μg, 30 μg 21 2 Injection site pain, fever (33% after the 2nd dose, 1 severe), fatigue, chills

Injection site redness: (20 μg:8%, 30 μg:8%)

Injection site swelling: (10 μg:8%, 20 μg:17%, 30 μg:25%)

 Peak at d2
7 Sahin, U. Phase 1/2 12 58.3 38.21 NM 1 μg 21 1&2 Injection site pain, fever, chills, headache, fatigue, muscle pain, joint pain, diarrhea Injection site: swelling(17%)

0–7,

22–28
7 Sahin, U. Phase 1/2 12 66.7 43.62 NM 10 μg 21 1&2 Injection site pain, fever, chills, headache, fatigue, muscle pain, joint pain, diarrhea Injection site: swelling(4%)

0–7,

22–28
7 Sahin, U. Phase 1/2 12 33.3 35.74 NM 30 μg 21 1&2 Injection site pain, fever, chills, headache, fatigue, muscle pain, joint pain, diarrhea Injection site: redness(54.1%), swelling(41.6%)

0–7,

22–28
7 Sahin, U. Phase 1/2 12 50 33.88 NM 50 μg 21 1&2 Injection site pain, fever, chills, headache, fatigue, muscle pain, joint pain, diarrhea, vomiting Injection site: redness(62.5%), swelling(50%)

0–7,

22–28
7 Sahin, U. Phase 1/2 12 41.7 35.81 NM 60 μg 21 1 Injection site pain, fever, chills, headache, fatigue, muscle pain, joint pain, diarrhea, vomiting Injection site: swelling(33%)

0–7,

22–28
8 Mulligan, M. J. Phase 1&2 12 50 35.8 NM 30 μg 21 1&2

Injection site pain, fever, fatigue, headache, chills, diarrhea, muscle pain, joint pain

Severe adverse events: (8.3%)

Injection site redness:(both doses: <20%)

Injection site swelling: (1st:<20%, 2nd:<30%)

 0–7, Peak at d2
8 Mulligan, M. J. Phase 1&2 12 58.3 38.3 NM 100 μg 21 1

Injection site pain, fever, fatigue, headache, chills, diarrhea, muscle pain, joint pain

Severe adverse events: (8.3%)

Injection site redness(<40%),

Injection site swelling(<50%)

 0–7, Peak atd2
1.4. mRNA‐1273 (n = 30,359)
9 Anderson, E. J. Phase 1 10 70 65.8 NM (56–70 years) 25 μg 28 1&2 Injection site pain, fever, headache, fatigue, arthralgia, myalgia, chills, nausea, Injection site erythema/redness(2nd ≤ 10%), swelling/induration(1st ≤ 10% and 2nd ≤ 20%) 0–1
9 Anderson, E. J. Phase 1 10 20 72.8 NM (≥71 years) 25 μg 28 1&2 Injection site pain, headache, fatigue, arthralgia, myalgia Injection site erythema/redness (2nd ≤ 20%), swelling/induration(2nd ≤ 20%), skin and subcutaneous tissue disorders (collective n = 3 in age group) 0–1
9 Anderson, E. J. Phase 1 10 50 63.8 NM (56–70 years) 100 μg 28 1&2 Injection site pain, fever, headache, fatigue, arthralgia, myalgia, chills, nausea, Injection site erythema/redness(2nd ≤ 10%), swelling/induration(2nd ≤ 20%) 0–1
9 Anderson, E. J. Phase 1 10 70 72.6 NM (≥71 years) 100 μg 28 1&2 Injection site pain, fever, headache, fatigue, arthralgia, myalgia, chills, nausea, Injection site erythema/redness(2nd ≤ 20%), swelling/induration(2nd ≤ 30%), skin and subcutaneous tissue disorders(collective n = 3 in age group) 0–1
10 Jackson, L. A. Phase 1 15 51 33 NM 25 μg 28 1 Injection site pain, fatigue, headache, myalgia, nausea Transient urticaria on both legs in one participant 5
10 Jackson, L. A. Phase 1 15 51 33 NM 100 μg 28 1 Injection site pain, arthralgia, fatigue, chills, headache, myalgia, Erythema/redness (13.4%), induration/swelling (13.3%) NM
10 Jackson, L. A. Phase 1 15 51 33 NM 100 μg 28 2 Injection site pain, fever, nausea, arthralgia, fatigue, chills, headache, myalgia Erythema/redness (13.4%), induration/swelling (6.7%) NM
10 Jackson, L. A. Phase 1 15 51 33 NM 250 μg 28 1 Injection site pain, arthralgia, fatigue, chills, headache, myalgia, nausea Erythema/redness (6.7%), induration/swelling (13.4%) NM
10 Jackson, L. A. Phase 1 14 51 33 NM 250 μg 28 2 Injection site pain, fever, arthralgia, fatigue, chills, headache, myalgia, nausea Erythema/redness (21.4%), induration/swelling (21.4%) NM
11 Chu, L. Phase 2 100 64 36.6 NM (≥18 ‐ < 55 years) 50 μg 28 1&2 Injection site pain,headache,fatigue,myalgia,arthralgia,nausea/vomiting,chills Local: erythema(1st:2%, 2nd:5%), swelling(1st:5%, 2nd:6%), axillary swelling /tenderness(1st:7%, 2nd:7%), generalized rash(1st:4%, 2nd:7%) 0–7
11 Chu, L. Phase 2 100 73 64.6 NM (≥55 years) 50 μg 28 1&2 Injection site pain,headache,fatigue,myalgia,arthralgia,nausea/vomiting,chills Local: erythema (1st:3%, 2nd:5%), swelling(1st:3%, 2nd:6%), axillary swelling /tenderness(1st:3%, 2nd:12%), generalized rash(1st:2%, 2nd:3%) 0–7
11 Chu, L. Phase 2 100 53 38.3 NM (≥18 ‐ < 55 years) 100 μg 28 1&2 Injection site pain,headache,fatigue,myalgia,arthralgia,nausea/vomiting,chills Local: erythema (1st:3%, 2nd:8%), swelling(1st:5%, 2nd:11%), axillary swelling /tenderness(1st:15%, 2nd:10%), generalized rash(1st:4%, 2nd:4%) 0–7
11 Chu, L. Phase 2 100 71 63.9 NM (≥55 years) 100 μg 28 1&2 Injection site pain, fever, headache, fatigue, myalgia, arthralgia, nausea/vomiting, chills Local: erythema(1st:2%, 2nd:7%), swelling(1st:3%, 2nd:10%), axillary swelling /tenderness(1st:3%, 2nd:10%), generalized rash(1st:1%, 2nd:2%) 0–7
12 Baden, L. R. Phase 3 15,168 47.8 51.4 CLD, Cardiac disease, Obesity, DM, Liver disease, HIV 100 μg 28 1 Injection site pain, fever, headache, fatigue, myalgia, arthralgia, nausea or vomiting, chills, serious adverse events: (<0.1%) Erythema (2.8%), swelling (6.1%), lymphadenopathy (10.2%), hypersensitivity (1.1%), urticaria (0.2%), rash (0.2%), contact dermatitis (0.2%) 2.6
12 Baden, L. R. Phase 3 14,677 47.8 51.4 CLD, Cardiac disease, Obesity, DM, Liver disease, HIV 100 μg 28 2 Injection site pain, fever, headache, fatigue, myalgia, arthralgia, nausea or vomiting, chills, serious adverse events: (<0.1%) Erythema (8.6%), swelling (12.2%), lymphadenopathy(14.2%), hypersensitivity (1.1%), urticaria (0.2%), rash (0.2%), contact dermatitis (0.2%) 3.2
2. Adenovirus viral vector vaccines

2.1. ChAdOx1 nCoV‐19 (n = 13,995) (SD: 3.5–6.5 [mostly 5] × 1010 virus particles, LD: 2.2 × 1010 viral particles)

13 Barrett, J. R. Phase 1/2 20 70 36 NM SD/SD 56 1&2 Injection site pain, chills, fatigue, fever, feverish, headache, joint pain, malaise, muscle ache, nausea Itch(1st& 2nd), tenderness(1st&2nd), warmth(1st& 2nd) 0–7
13 Barrett, J. R. Phase 1/2 32 52 44 NM SD/LD 56 1&2 Injection site pain, chills, fatigue, fever, feverish, headache, joint pain, malaise, muscle ache, nausea Induration(1st), itch(1st& 2nd), redness(1st& 2nd), swelling(2nd), tenderness(1st& 2nd), warmth(1st& 2nd) 0–7
14 Folegatti, P. M. Phase 1/2 487 49 34 NM SD single 1 Injection site pain, feverishness,fever, chills,joint pain,muscle ache,fatigue,headache,malaise,nausea Local: redness(3%), warmth(25%), itch(7%), swelling(4%), induration(3%), tenderness(83%) 0‐7 peak at d1
14 Folegatti, P. M. Phase 1/2 56 49 34 NM SD + prophylactic paracetamol single 1 Injection site pain, feverishness,fever, chills,joint pain,muscle ache,fatigue,headache,malaise,nausea Local: redness(2%), warmth (20%), itch(12%), swelling(2%), tenderness(77%) 0–7 peak at d1
14 Folegatti, P. M. Phase 1/2 10 49 34 NM SD single 1&2 Injection site pain, feverishness,fever, chills,joint pain,muscle ache,fatigue,headache,malaise,nausea Local: warmth(20%), itch(10%), tenderness(50%) (after both doses) 0–7 peak at d1
15 Madhi, S. A. Phase 1b–2 1011 43.2 31 Obesity(18.8%), current smoker (42.9%), HTN (3.1%), Chronic respiratory condition (3.5%), DM (0.4%) SD 21–35 1&2 Cough, feverish, headache, joint pain, muscle pain, sweating, tenderness, weakness Injection site: redness, swelling, bruising, hardness,mild itching, epidermal and dermal conditions(0.9%), skin appendage conditions(0.5%), angioedema and urticaria(0.2%), dental and gingival conditions(0.2%), oral soft tissue conditions(0.4%), allergic conditions(0.2%) 0–6
16 Frater, J., Phase 2/3 54 0 42.5 HIV + NM 28–56 1&2 Injection site pain,feverish, fever, chills, joint pain, muscle ache, fatigue, headache, malaise, nausea Local: warmth(1st:11.3%, 2nd:5.9%), itch(1st:3.8%, 2nd:2%), swelling(1st:1.9%), induration(1st:1.9%), tenderness(1st:62.3%, 2nd:43.1%) 0–7
16 Frater, J., Phase 2/3 50 48 38.5 HIV ‐ NM 28–56 1&2 Injection site pain,feverish, fever, chills, joint pain, muscle ache, fatigue, headache, malaise, nausea Local: redness(2nd:2.0%), warmth(1st:16%, 2nd:12.2%), itch(1st:4.0%, 2nd:12.2%), tenderness(1st:76.0%, 2nd:61.2%) 0–7
17 Ramasamy, M. N. Phase 2/3 50 70 44.5 NM (18–55 years) SD/SD 28 1&2 Injection site pain,tenderness, feverish, fever, chills, joint pain, muscle ache, fatigue, headache, malaise, nausea Injection site: redness(2nd:2%), warmth(1st:14%, 2nd:12%), itch(1st:4%, 2nd:12%) 0–7
17 Ramasamy, M. N. Phase 2/3 30 33 60.4 NM (56–69 years) SD/SD 28 1&2 Injection site pain,tenderness, feverish, chills, joint pain, muscle ache, fatigue, headache, malaise, nausea Injection site: warmth(1st:7%, 2nd:14%), itch(1st:7%, 2nd:3%) 0–7
17 Ramasamy, M. N. Phase 2/3 46 35 73 NM (≥70 years) SD/SD 28 1&2 Injection site pain,tenderness, feverish, chills, joint pain, muscle ache, fatigue, headache, malaise, nausea Injection site: redness(1st:2%, 2nd:2%), warmth(1st:14%, 2nd:4%), itch(1st:4%, 2nd:2%), swelling(1st:4%, 2nd:4%), induration(1st:2%, 2nd:2%) 0–7
17 Ramasamy, M. N. Phase 2/3 49 47 39 NM (18–55 years) LD/LD 28 1&2 Injection site pain,tenderness, feverish, chills, joint pain, muscle ache, fatigue, headache, malaise, nausea Injection site: redness(2nd:2%), warmth(1st:18%, 2nd:6%), itch(1st:4%, 2nd:2%) 0–7
17 Ramasamy, M. N. Phase 2/3 30 53 59.5 NM (56–69 years) LD/LD 28 1&2 Injection site pain,tenderness, feverish, fever, chills, joint pain, muscle ache, fatigue, headache, malaise, nausea Injection site: warmth(1st:3%), itch(1st: 7%) 0–7
17 Ramasamy, M. N. Phase 2/3 49 43 73 NM (≥70 years) LD/LD 28 1&2 Injection site pain,tenderness, feverish, fever, chills, joint pain, muscle ache, fatigue, headache, malaise, nausea Injection site: redness(1st:2%, 2nd:4%), warmth(1st:2%, 2nd:2%), itch(1st:2%), swelling(1st:2%, 2nd:4%), induration(1st:2%, 2nd:4%) 0–7
18 Voysey, M. Different phases (1,2,3) 12,021 56 NM CVD, Respiratory disease, DM, some Baseline COVID + (18–55 years, 56–69 years, 70+ years) SD/SD or LD/SD 28 1&2 Cardiac, sensory, GI, general and injection site, procedural complications, infections and infestations, neoplasms, nervous system, renal and urinary, musculoskeletal and connective tissue, reproductive, respiratory side effects Cellulitis1 (<0.1%),anaphylactic reaction1 (<0.1%),psoriasis 1 (<0.1%), rosacea 1 (<0.1%), vitiligo 1 (<0.1%), Raynaud's phenomenon 1 (<0.1%), uveitis 2 (<0.1%) any time during study
2.2.Gam‐COVID‐Vac (n = 15,011) (all 1 × 1011 viral particles)
19 Logunov, D. Y. Phase 1/2 9 78 27 NM LyophilisedrAd5‐S 21 1&2 Injection site pain, hyperthermia,headache,muscle and joint pain,changes in laboratory variables Local: edema(11%), hyperthermia(11%),mucosal abnormality 0–28
19 Logunov, D. Y. Phase 1/2 9 0 27.8 NM rAd26‐S 21 1&2 Injection site pain, hyperthermia,headache,asthenia,muscle and joint pain,heartbeat (subjective palpitation),diarrhea,loss of appetite,changes in laboratory variables Local: itch(11%), generalized: hives(11%) 0–28
19 Logunov, D. Y. Phase 1/2 9 44 31.4 NM LyophilisedrAd26‐S 21 1&2 Injection site pain, hyperthermia,headache,muscle and joint pain,changes in laboratory variables Local: edema(22%) 0–28
19 Logunov, D. Y. Phase 1/2 20 30 26.4 NM

rAd26‐S plus rAd5‐S

(heterologous prime‐boost)

 21 1&2 Injection site pain, hyperthermia,headache,asthenia,muscle and joint pain,diarrhea,rhinorrhea,loss of appetite,pain in the oropharynx, malaise,sore throat, nasal congestion, cough, sneezing, changes in laboratory variables Local: hyperthermia(10%), swelling(5%) 0–28
20 Logunov, D. Y. Phase 3 14,964 38.9 45.3 DM, HTN, IHD, Obesity

rAd26‐S plus rAd5‐S

(heterologous prime‐boost)

 21 1&2 Vascular disorders, infections and invasions, reproductive, heart disorders, injury, intoxication and complications of procedures, GI, renal, liver and biliary tract, muscle, skeletal and connective tissue and nervous system side effects Hypersensitivity (0.01%), acne‐form dermatitis (0.01%), allergic skin reaction(0.01%), allergic rash(0.05%), alopecia(0.02%), itching (0.04%), skin rash (0.1%), petechial rash(0.01%), rash(0.03%), eczema (0.01%), keratoconjunctivitis(0.01%),chalazion (0.01%), allergic reaction (0.15%), herpes (0.09%), benign neoplasm of the eyelid (0.01%), axillary lymphadenitis (0.07%) any time during study
2.3. Ad5‐nCoV (n = 490) (LD: 5 × 1010 viral particles, MD: 1 × 1011 viral particles, HD: 1.5 × 1011 viral particles)
21 Zhu, F. C. Phase 1 36 of 108 49 36.3 Baseline COVID + (0%) LD single 1 Injection site pain, fever, headache, fatigue, vomiting, diarrhea, muscle pain, joint pain, throat pain, cough, nausea, impaired appetite, functional gi disorder,dizziness Injection site: induration(6%), redness(6%), swelling(11%), itch (6%), general pruritis: (3%) 0–7
21 Zhu, F. C. Phase 1 36 of 108 49 36.3 Baseline COVID + (0%) MD single 1 Injection site pain, fever, headache, fatigue, diarrhea, muscle pain, joint pain, throat pain, cough, nausea, impaired appetite Injection site: induration(3%), redness(3%), swelling(11%), itch(8%), general pruritis:(3%) 0–7
21 Zhu, F. C. Phase 1 36 of 108 49 36.3 Baseline COVID + (0%) HD single 1 Injection site pain, fever, headache, fatigue (6% grade 3), vomiting, diarrhea, muscle pain (3% grade 3), joint pain (3% grade 3), muscular weakness, throat pain, cough, nausea, impaired appetite, dyspnoea (3% grade 3), dizziness Injection site: induration(3%), redness(3%), general pruritis:(3%), mucosal abnormality (3%) 0–7
22 Zhu, F. C. Phase 2 253 50 40 Underlying diseases (3%), Baseline COVID + (0%) MD single 1 Injection site pain, fever, headache, fatigue, vomiting, diarrhea, muscle pain, joint pain, oropharyngeal pain, cough, nausea, dyspnoea, appetite impaired, syncope Injection site reactions: induration (5%), redness (2%), swelling (4%), itching (6%), general: pruritus (2%) 0–14
22 Zhu, F. C. Phase 2 129 50 39.7 Underlying diseases (6%), Baseline COVID + (0%) LD single 1 Injection site pain, fever, headache, fatigue, vomiting, diarrhea, muscle pain, joint pain, oropharyngeal pain, cough, nausea, dyspnoea, appetite impaired, syncope Injection site reactions: induration (2%), redness (1%), swelling (4%), itching (2%), general: pruritus (3%) mucosal abnormality 0–14

2.4. Ad26.COV2.S (n = 22,537) (LD: 5 × 1010 viral particles, HD: 1 × 1011 viral particles)

23 Sadoff, J., Phase 1–2a 162 52 36.1 NM 18–55 years LD 56 1&2 Injection site pain, fatigue, headache, myalgia, nausea, pyrexia Local: erythema (<5%), swelling(<5%) 0–28
23 Sadoff, J., Phase 1–2a 158 54 34.8 NM 18–55 years HD 56 1&2 Injection site pain, fatigue, headache, myalgia, nausea, pyrexia Local: erythema(<5%), swelling(<5%) 0–28
23 Sadoff, J., Phase 1–2a 161 48 69.6 NM ≥ 65 years LD 56 1&2 Injection site pain, fatigue, headache, myalgia, nausea, pyrexia Local: erythema(<10%), swelling(<10%) 0–28
23 Sadoff, J., Phase 1–2a 161 51 70 NM ≥ 65 years HD 56 1&2 Injection site pain, fatigue, headache, myalgia, nausea, pyrexia Local: erythema(<10%), swelling(<10%) 0–28
24 Sadoff, J. Phase 3 21,895 44.9 52 Baseline COVID + (9.8%), Obesity (28.6%) LD 56 1 Injection site pain, headache, fatigue, myalgia, nausea, fever Local: erythema (0.23%), swelling(0.2%), urticaria (n = 8), hypersensitivity(n = 9) 0–7
3. Protein subunit vaccines
3.1. NVX‐CoV2373 (n = 1060) (Ad: Adjuvant 50 μg Matrix‐M1)
25 Shinde, V. Phase 1 334 43.1 (all 2199) 31.9 (all 2199) HTN, DM, HIV, Baseline COVID + (0%) 5 μg + Ad 21 1 Injection site pain and tenderness, fever, headache, fatigue, malaise, joint pain, muscle pain,nausea or vomiting Injection site: erythema(1.5%), swelling(1.2%) 0–6
25 Shinde, V. Phase 1 329 43.1 (all 2199) 31.9 (all 2199) HTN, DM, HIV, Baseline COVID + (0%) 5 μg + Ad 21 2 Injection site pain and tenderness, fever, headache, fatigue, malaise, joint pain, muscle pain,nausea or vomiting Injection site: erythema(1.8%), swelling(2.7%) 21–27
25 Shinde, V. Phase 1 150 43.1 (all 2199) 31.9 (all 2199) HTN, DM, HIV, Baseline COVID +(100%) 5 μg + Ad 21 1 Injection site pain and tenderness, fever, headache, fatigue, malaise, joint pain, muscle pain,nausea or vomiting Injection site: erythema(1.3%), swelling(4%) 0–6
25 Shinde, V. Phase 1 142 43.1 (all 2199) 31.9 (all 2199) HTN, DM, HIV, Baseline COVID +(100%) 5 μg + Ad 21 2 Injection site pain and tenderness, fever, headache, fatigue, malaise, joint pain, muscle pain,nausea or vomiting Injection site: swelling(0.7%) 21–27
26 Keech, C. Phase 1/2 25 52 27.2 NM 25 μg, Un‐adjuvanted 21 1&2 Injection site pain, arthralgia,fatigue,malaise,headache,myalgia,nausea or vomiting Local: erythema or redness(2nd:4%), induration or swelling(2nd:4%) 0–7
26 Keech, C. Phase 1/2 26 50 29.5 NM 5 μg + Ad 21 1&2 Injection site pain, arthralgia,fatigue,malaise,headache,myalgia,nausea or vomiting Local: erythema or redness(2nd:7.6%), induration or swelling(2nd:3.8%),skin and subcutaneous tissue disorders(3.8%) 0–7
26 Keech, C. Phase 1/2 3 33.3 23.7 NM 5 μg + Ad 21 1&2 Injection site pain, fatigue,malaise,headache,myalgia Local: erythema or redness(1st:33.3%,2nd:33.3%) 0–7
26 Keech, C. Phase 1/2 25 32 35.6 NM 25 μg + Ad 21 1&2 Injection site pain, arthralgia,fatigue,malaise,fever,headache,myalgia,nausea or vomiting Local: induration or swelling(2nd:8.3%)skin and subcutaneous tissue disorders(4%), rash(4%) 0–7
26 Keech, C. Phase 1/2 26 65.4 33 NM

1st: 25 μg + Ad

2nd: placebo

 21 1&2 Injection site pain, arthralgia,fatigue,malaise,headache,myalgia,nausea or vomiting Local: erythema or redness(1st:3.8%,2nd:3.8%)skin and subcutaneous tissue disorders(7.7%) 0–7
3.2. MF59‐adjuvanted sclamp (n = 96)
27 Chappell, K. J. Phase 1 24 54 34.1 NM 5 μg 28 1&2 Injection site pain, chills, nausea, vomiting, fever, headache, fatigue/somnolence, myalgia, arthralgia, malaise

Local: tenderness(1st:50.0%, 2nd:62.5%), induration/swelling(1st:8.3%);

Alopecia (4.2%), pruritis (4.2%)

 0–7
27 Chappell, K. J. Phase 1 24 54 31 NM 15 μg 28 1&2 Injection site pain, nausea, vomiting, headache, fatigue/somnolence, diarrhea, myalgia, arthralgia, malaise Local: tenderness(1st:54.2%, 2nd:58.3%), induration/swelling(1st:8.3%) 0–7
27 Chappell, K. J. Phase 1 1st: n = 48 2nd: n = 24 33.5 32.3 NM 45 μg 28 1&2 Injection site pain, chills, nausea, vomiting, headache, fatigue/somnolence, diarrhea, myalgia, arthralgia, malaise

Local: tenderness(1st:47.9%, 2nd:58.3%), erythema/redness (1st:2.1%), induration/swelling(1st:4.2%);

Macular rash(4.2%), contact dermatitis(4.2%)

 0–7
3.3. SCB‐2019 (n = 88)
28 Richmond, P. Phase 1 8 38 35.8 NM (18–54 years) 3 μg + AS03 21 1&2 Injection site pain, fever, headache, myalgia, nausea, vomiting, fatigue Local: erythema (12.5%) 0–7
28 Richmond, P. Phase 1 8 38 62.8 NM (55–75 years) 3 μg + AS03 21 1&2 Injection site pain, headache, fatigue Local: erythema (6.25%), swelling(6.25%) 0–7
28 Richmond, P. Phase 1 8 100 41.9 NM (18–54 years) 3 μg + CpG/Alum 21 1&2 Injection site pain, headache, myalgia, nausea, fatigue Local: erythema (6.25%), swelling(6.25%) 0–7
28 Richmond, P. Phase 1 8 50 37 NM (18–54 years) 9 μg + AS03 21 1&2 Injection site pain, fever, headache, myalgia, fatigue Local: erythema (6.25%), swelling (18.75%) 0–7
28 Richmond, P. Phase 1 8 38 59.1 NM (55–75 years) 9 μg + AS03 21 1&2 Injection site pain fever headache myalgia fatigue Local: erythema (25%), swelling(18.75%) 0–7
28 Richmond, P. Phase 1 8 50 36.1 NM (18–54 years) 9 μg + CpG/Alum 21 1&2 Injection site pain, headache, myalgia, fatigue Local: erythema (12.5%), swelling(6.25%) 0–7
28 Richmond, P. Phase 1 8 38 60.3 NM (55–75 years) 9 μg + CpG/Alum 21 1&2 Injection site pain, fever, headache, myalgia, fatigue Local: erythema (6.7%), swelling(6.7%) 0–7
28 Richmond, P. Phase 1 8 75 31.3 NM (18–54 years) 30 μg + AS03 21 1&2 Injection site pain, fever, headache, myalgia, diarrhea, nausea, vomiting, fatigue Local: erythema (6.25%), swelling(18.75%) 0–7
28 Richmond, P. Phase 1 8 75 59.8 NM (55–75 years) 30 μg + AS03 21 1&2 Injection site pain, headache, myalgia, diarrhea nausea, vomiting Local: erythema (6.25%), swelling(6.25%) 0–7
28 Richmond, P. Phase 1 8 75 39.1 NM (18–54 years) 30 μg + CpG/Alum 21 1&2 Injection site pain, headache, fatigue Local: erythema (18.75%), swelling(6.25%) 0–7
28 Richmond, P. Phase 1 8 50 61.5 NM (55–75 years) 30 μg + CpG/Alum 21 1&2 Injection site pain, myalgia, fatigue Local: swelling(6.25%) 0–7
3.4. CoV2 preS dTM (n = 336) (LD: 1.3 μg, HD: 2.6 μg)
29 Goepfert, P. A. Phase 1/2 18 50 35.3 NM (18–49 years) LD + AF03 21 1&2 Injection site pain, fever, headache, malaise, myalgia

1st: injection site: erythema(6.3%)

2nd: injection site: erythema(12.5%), swelling(18.8%)

 0–7
29 Goepfert, P. A. Phase 1/2 54 46 33.7 NM (18–49 years) LD + AS03 21 1&2 Injection site pain, fever, headache, malaise, myalgia

1st: injection site:swelling(2%)

2nd: injection site: erythema(19.6%), swelling(15.7%)

 0–7
29 Goepfert, P. A. Phase 1/2 28 39 59.8 NM (≥50 years) LD + AS03 21 1&2 Injection site pain, fever, headache, malaise, myalgia

1st: injection site: erythema(3.6%)

2nd: injection site: erythema(32.1%),swelling(25%)

 0–7
29 Goepfert, P. A. Phase 1/2 17 65 32.5 NM (18–49 years) HD + AF03 21 1&2 Injection site pain, fever, headache, malaise, myalgia 2nd: injection site: erythema(17.6%), swelling(17.6%) 0–7
29 Goepfert, P. A. Phase 1/2 10 70 58.7 NM (≥50 years) HD + AF03 21 1&2 Injection site pain, headache, malaise, myalgia

1st: injection site: erythema(11.1%)

2nd: injection site: erythema(11.1%),swelling(11.1%)

 0–7
29 Goepfert, P. A. Phase 1/2 54 43 34.9 NM (18–49 years) HD + AS03 21 1&2 Injection site pain, fever, headache, malaise, myalgia

1st: injection site: erythema(3.7%),swelling(7.4%)

2nd: injection site: erythema(50%),swelling(33.3%)

 0–7
29 Goepfert, P. A. Phase 1/2 31 68 61.7 NM (≥50 years) HD + AS03 21 1&2 Injection site pain, fever, headache, malaise, myalgia

1st: injection site: erythema(6.5%),swelling(3.2%)

2nd: injection site: erythema(32.3%),swelling(25.8%)

 0–7
29 Goepfert, P. A. Phase 1/2 18 56 34.8 NM (18–49 years) HD Un‐adjuvanted 21 1&2 Injection site pain, headache, malaise, myalgia 2nd: injection site: erythema(5.9%),swelling(5.9%) 0–7
29 Goepfert, P. A. Phase 1/2 24 58 36 NM (18–49 years) LD + AF03 single 1 Injection site pain, headache, malaise, myalgia Injection site: erythema(3.8%), swelling(3.8%) 0–7
29 Goepfert, P. A. Phase 1/2 10 80 59.3 NM (≥50 years) LD + AF03 single 1 Injection site pain, headache, malaise, myalgia Injection site: erythema(10%) 0–7
29 Goepfert, P. A. Phase 1/2 24 38 35.4 NM (18–49 years) LD + AS03 single 1 Injection site pain, headache, malaise, myalgia Injection site: swelling(7.7%) 0–7
29 Goepfert, P. A. Phase 1/2 24 54 32 NM (18–49 years) HD + AF03 single 1 Injection site pain, headache, malaise, myalgia Injection site: swelling(4.3%) 0–7
29 Goepfert, P. A. Phase 1/2 24 58 29.7 NM (18–49 years) HD + AS03 single 1 Injection site pain, headache, malaise, myalgia Injection site: erythema(12.5%), swelling(8.3%) 0–7
3.5. ZF2001(n = 640)
30 Yang, S. Phase 1 20 30 31.7 NM 25 μg 30 1&2&3 Injection site pain, fever, headache, cough, muscle pain Swelling(5%), induration(10%), redness(20%), itch(20%) 0–7
30 Yang, S. Phase 1 20 45 33.6 NM 50 μg 30 1&2&3 Injection site pain, headache, fatigue, weakness, cough, nausea Swelling(15%), induration(25%), redness(20%, 5% grade ≥3), rash(5%), itch(35%) 0–7
30 Yang, S. Phase 2 150 57 43.04 NM 25 μg 30 1&2 Injection site pain, fever, headache, fatigue, cough, nausea, muscle pain Swelling(4%), induration(3%), redness(8%), rash(2%), itch(6%) 0–7
30 Yang, S. Phase 2 150 62 44.4 NM 50 μg 30 1&2 Injection site pain, fever, headache, fatigue, cough Swelling(6%), induration(5%), redness(8%, 1% grade ≥3), rash(3%), itch(9%) 0–7
30 Yang, S. Phase 2 150 53 42.7 NM 25 μg 30 1&2&3 Injection site pain, fever, headache, cough, muscle pain Swelling(14%), induration(9%), redness(16%, 1% grade ≥3), rash(1%), itch(19%) 0–7
30 Yang, S. Phase 2 150 58 43.2 NM 50 μg 30 1&2&3 Injection‐site pain, fever, nausea Swelling(13%, 2% grade ≥3), induration(7%, 1% grade ≥3), redness(14%, 3% grade ≥3), rash(1%, grade ≥3), itch(17%) 0–7
3.6. V‐01 (n = 24)
31 Zhang, J. Phase 1 24 75 40 NM 10 μg 21 1&2 Injection site pain, fever, anorexia, vomiting, nausea, headache, fatigue Local: pruritus(4.17%) 0–30
4. Inactivated virus vaccines
4.1. CoronaVac (n = 7497)
32 Wu, Z. Phase 1 24 54 65.6 NM 3 μg 28 1&2 Injection site pain, muscle pain, fatigue, nausea, fever, abdominal distention Injection site pruritus(4.2%), hypersensitivity(4.2%) 0–28
32 Wu, Z. Phase 1 24 46 67.5 NM 6 μg 28 1&2 Injection site pain, muscle pain, fatigue,headache, decreased appetite, cough Injection site pruritus(4.2%),mucocutaneous eruption(8.3%), rash(4.2%) 0–28
32 Wu, Z. Phase 2 100 51 66.8 NM 1.5 μg 28 1&2 Injection site pain,fever, fatigue, diarrhea, cough Injection site: erythema(2%), pruritus(1%) 0–28
32 Wu, Z. Phase 2 100 51 66.5 NM 3 μg 28 1&2 Injection site pain, fever, fatigue, diarrhea, cough Injection site: swelling(1%) 0–28
32 Wu, Z. Phase 2 99 55 66.2 NM 6 μg 28 1&2 Injection site pain Injection site: erythema(1%), swelling(1%) 0–28
33 Zhang, Y. Phase 1 24 58.3 45 NM 6 μg 14 1&2 Injection site pain, fatigue, diarrhea, fever, abdominal pain Injection site discoloration(4.2%), acute hypersensitivity with manifestation of urticaria (1st dose, one case, 4% of 24), general hypersensitivity(4.2%) Mostly 0–2
33 Zhang, Y. Phase 2 120 55 42 NM 3 μg 14 1&2 Injection site pain, fatigue, fever, diarrhea, nausea, headache, muscle pain,vomiting, chest pain,dizziness, decreased appetite Injection site: swelling(1.7%), redness(0.8%)hypoaesthesia(0.8%),pruritus(0.8%),induration(0.8%) Mostly 0–2
33 Zhang, Y. Phase 2 120 60 42.4 NM 6 μg 14 1&2 Injection site pain, fatigue, fever, diarrhea, nausea, headache, muscle pain,cough,chest pain, drowsiness,palpitations Injection site: swelling (2.5%), redness (1.7%), hypoaesthesia (0.8%), discoloration (0.8%), pruritus (0.8%), general hypersensitivity (0.8%) Mostly 0–2
33 Zhang, Y. Phase 2 120 47.5 41.5 NM 3 μg 28 1&2 Injection site pain, fatigue, fever, diarrhea,headache, muscle pain,cough General hypersensitivity (0.8%) Mostly 0–2
33 Zhang, Y. Phase 2 120 47.5 40.6 NM 6 μg 28 1&2 Injection site pain, fatigue, fever, diarrhea,headache, muscle pain,decreased appetite Injection site: swelling (0.8%), redness (0.8%), discoloration (0.8%), pruritus (0.8%) Mostly 0–2
34 Tanriover, M. D. Phase 3 6646 42.6 45 HTN, CVD, Chronic respiratory disease, DM, Malignancy, Autoimmune 3 μg 14 1&2 Injection site: pain and paraesthesia, fatigue, headache, myalgia, chill, fever, diarrhea, cough, arthralgia, nausea, vomiting, seizure(n = 1),encephalitis(n = 1) Injection site: erythema(0.18%), swelling(0.06%), induration(0.05%), pruritus(0.03%), generalized: rash(0.11%), allergic reaction(0.08%), pruritis and swelling (<0.0%), redness and swelling in the mouth(n = 1) 0‐unblinding
4.2. WIBP‐CorV (n = 132)
35 Xia, S. Phase 1 24 54.2 36 Baseline COVID + (0%) 2.5 μg 28 1&2&3 Injection site pain Local: swelling(4.2%) 0–28
35 Xia, S. Phase 1 24 54.2 43.1 Baseline COVID + (0%) 10 μg 28 1&2&3 Injection site pain,fever,nausea and vomiting, anorexia Local: redness(4.2%), swelling(4.2%) 0–28
35 Xia, S. Phase 2 84 61.9 43.8 Baseline COVID + (0%) 5 μg 21 1&2 Injection site pain, diarrhea, fever, nausea and vomiting Local: itching(1.2%), swelling(1.2%) 0–28
4.3. BBIBP‐CorV (n = 27,367)
36 Xia, S. Phase 1 24 66 42.7 NM (18–59 years) 2 μg, HB02 strain 28 1&2 Injection site pain, fever,fatigue,headache Injection site: redness(4%), mucocutaneous abnormalities(4%),itch (non‐injection site)(4%) 0–7
36 Xia, S. Phase 1 24 50 37.7 NM (18–59 years) 4 μg, HB02 strain 28 1&2 Injection site pain, fever, vomiting Injection site: itch (4%) 0–7
36 Xia, S. Phase 1 24 47 40.1 NM (18–59 years) 8 μg, HB02 strain 28 1&2 Injection site pain, fever, inappetence, nausea, constipation Injection site: swelling (8%) 0–7
36 Xia, S. Phase 1 24 72 67.5 NM (≥60 years) 8 μg, HB02 strain 28 1&2 Injection site pain, fever, fatigue,headache Injection site: induration (8%) 0–7
36 Xia, S. Phase 2 84 54 40.8 NM (18–59 years) 8 μg, HB02 strain single 1 Injection site pain, fever, fatigue,headache, diarrhea, muscle pain, dizziness, anaphylaxis(1%) Injection site: swelling(2%),itch(2%),redness(1%),rash(1%) 0–7
36 Xia, S. Phase 2 84 55 41 NM (18–59 years) 4 μg, HB02 strain 14 1&2 Injection site pain, fever, fatigue,headache, diarrhea, muscle pain Injection site:itch(1%),itch (non‐injection site)(2%) 0–7
36 Xia, S. Phase 2 84 53 41.7 NM (18–59 years) 4 μg, HB02 strain 21 1&2 Injection site pain, fever, fatigue,nausea,headache, drowsiness Injection site: swelling(4%),redness(1%) 0–7
36 Xia, S. Phase 2 84 57 43.7 NM (18–59 years) 4 μg, HB02 strain 28 1&2 Injection site pain, fever fatigueheadache, cough Injection site: swelling(1%),itch(1%),redness(1%), itch (non‐injection site)(1%) 0–7
37 Al Kaabi, N. Phase 3 13,464 15.9 36.2 Baseline COVID PCR + (0.2%), Baseline IgG +(5.0%) 5 μg, WIV04 strain 21 1&2 Injection site pain, headache, fatigue, myalgia, diarrhea, coughing, fever, dyspnea, arthralgia, constipation, nausea, vomiting, dysphagia, anorexia Injection site: induration(1.0%), swelling(1.5%), rash(0.7%), redness (1.1%), itching(0.4%), pruritus (non‐inoculated site)(1.3%), skin and mucosal abnormalities(0.2%), acute allergic reactions(0.3%) 0–7
37 Al Kaabi, N. Phase 3 13,471 15.4 36.2 Baseline COVID PCR + (0.2%), Baseline IgG +(5.2%) 4 μg, HB02 strain 21 1&2 Injection site pain, headache, fatigue, myalgia, diarrhea, coughing, fever, dyspnea, arthralgia, constipation, nausea, vomiting, dysphagia, anorexia Injection site: induration(0.6%), swelling(0.8%), rash(0.7%), redness(0.9%), itching(0.5%), pruritus (non‐inoculated site)(1.5%), skin and mucosal abnormalities(0.2%), acute allergic reactions(0.3%) 0–7
4.4. BBV152 (n = 380)
38 Ella, R. Phase 1/2 190 26 34 NM 3 μg + Algel‐IMDG 14 1&2 Injection site pain, body ache, fever, headache, malaise Redness at injection site (1st:1%), itching (1st:1%), stiffness in upper arm(1st:1%) 0–7
38 Ella, R. Phase 1/2 190 24 35 NM 6 μg + Algel‐IMDG 14 1&2 Injection site pain, weakness in injection arm, body ache, fever, headache, malaise, weakness Redness at injection site (1st:1%), itching(1st:1%, 2nd:1%),rashes(1st:1%) 0–7
4.5. KCONVAC (n = 424)
39 Pan, H. X. Phase 1 24 50 38 NM 5 μg 14 1&2 Injection site pain,myalgia, fatigue Injection site:induration(4%), erythema(8%) 0–28
39 Pan, H. X. Phase 2 100 47 45.5 NM 5 μg 14 1&2 Injection site pain,fever, inappetence, myalgia, headache, fatigue Injection site:induration(2%), erythema(1%), pruritus(2%) 0–28
39 Pan, H. X. Phase 2 100 55 44.9 NM 10 μg 14 1&2 Injection site pain,fever, diarrhea, inappetence, vomiting, myalgia, headache, cough, dyspnea, fatigue Injection site:pruritus(1%), skin or mucosa abnormality(1%) 0–28
39 Pan, H. X. Phase 2 100 62 42.4 NM 5 μg 28 1&2 Injection site pain,fever, diarrhea, myalgia, headache, cough, fatigue Injection site:erythema(1%), pruritus(1%) 0–28
39 Pan, H. X. Phase 2 100 54 44.5 NM 10 μg 28 1&2 Injection site pain,fever, diarrhea, nausea, cough, fatigue Injection site:induration(%3), swelling(2%), erythema(5%), pruritus(2%) 0–28
4.6. IBMCAMS vaccine (n = 96) (LD: 50EU, MD: 100EU)
40 Pu,J. Phase 1 24 54 37 NM LD 14 1 Injection site pain, fatigue, fever, serious adverse events (8.3%) Injection site itching (8.3%), rash (4.2%) 0–7
40 Pu,J. Phase 1 24 54 37 NM LD 14 2 Injection site pain, fatigue Injection site redness (4.2%) 0–7
40 Pu,J. Phase 1 24 67 38.2 NM MD 14 2 Injection site pain, fatigue, diarrhea Injection site itching (4.2%) 0–7
40 Pu,J. Phase 1 24 50 40.1 NM MD 28 2 Injection site pain, fatigue, fever, serious adverse events (8.3%) Injection site swelling (4.2%) 0–7
5. Virus‐like particle vaccines
5.1. CoVLP (n = 180)
41 Ward, B. J. Phase 1 20 55 34.9 NM 3.75 μgUn‐adjuvanted 21 1&2 Injection site pain, headache, fatigue, chills, discomfort or uneasiness

Injection site: redness (5%), swelling(5%), swelling in neck(5%)

0‐21d: allergicconjunctivitis (5%), maculo‐papular rash (5%)

 0–7
41 Ward, B. J. Phase 1 20 50 35.3 NM 3.75 μg + CpG 21 1&2 Injection site pain, fever, headache, muscle aches fatigue, chills, discomfort or uneasiness

Injection site: redness (5%), swelling(1st:5%, 2nd: 15%) swelling in neck(1st:20%, 2nd: 5%), chest wall (5%);

0‐21d: hordeolum(5%), plantar fasciitis(5%)

 0–7
41 Ward, B. J. Phase 1 20 75 34.7 NM 3.75 μg + AS03 21 1&2 Injection site pain, fever, headache, muscle aches, joint aches, fatigue, chills, discomfort or uneasiness

Injection site: redness (1st:5%, 2nd:31.6%), swelling(1st:15%, 2nd: 31.6%), swelling in neck(5.3%);

0‐21d: bacterial vaginosis(5%), vaginal infection (5%)

 0–7
41 Ward, B. J. Phase 1 20 50 35.6 NM 7.5 μg Un‐adjuvant 21 1&2 Injection site pain, headache, muscle aches, joint aches fatigue, chills

Injection site: swelling(5%); swelling in neck (5%), axilla (5%), groin(5%);

0‐21d: rash(5%)

 0–7
41 Ward, B. J. Phase 1 20 60 32.4 NM 7.5 μg + CpG 21 1&2 Injection site pain, fever, headache, muscle aches, fatigue, chills, discomfort or uneasiness

Injection site: redness (5%), swelling(1st:20%, 2nd:15%), swelling in neck (5%)

0‐21d: vulvovaginal pruritus(5%), contact dermatitis (5%), erythema(5%)

 0–7
41 Ward, B. J. Phase 1 20 60 37.2 NM 7.5 μg + AS03 21 1&2 Injection site pain, fever, headache, muscle aches, joint aches, fatigue, chills, discomfort or uneasiness

Injection site: redness(35%), swelling(1st:30%, 2nd:40%); swelling in neck(1st:5, 2nd:10), axilla(5%), groin(5%), chest wall(5%);

0‐21d: lymphadenopathy(5%), injection site papule(5%)

 0–7
41 Ward, B. J. Phase 1 20 65 34.1 NM 15 μg Un‐adjuvanted 21 1&2 Injection site pain, headache, muscle aches, fatigue

Swelling in neck (10%);

0‐21d: oral herpes(5%), dyshidrotic eczema(5%)

 0–7
41 Ward, B. J. Phase 1 20 50 32 NM 15 μg + CpG 21 1&2 Injection site pain, fever, headache, muscle aches, joint aches, fatigue, chills, discomfort or uneasiness

Injection site: swelling(1st:10%, 2nd:5.3%); swelling in neck(1st:5%, 2nd:5.3%), axilla(5.3%), chest wall (5%);

0‐21d:hot flush(5%)

 0–7
41 Ward, B. J. Phase 1 20 45 32.7 NM 15 μg + AS03 21 1&2 Injection site pain, fever, headache, muscle aches, joint aches, fatigue, chills, discomfort or uneasiness

Injection site: redness (1st:5%, 2nd:20%), swelling(1st:20%, 2nd:25%); swelling in neck(1st:10%, 2nd:15%), axilla(1st:10%, 2nd:10%);

0–21 d:injection sitebruising(5%), erythema(5%), warmth(5%), swelling(5%)

 0–7

Abbreviations: 1st, after the first dose; 2nd, after the second dose; CLD, chronic lung disease; CVD, cardiovascular disease; d, days; DM, diabetes mellitus; GI, gastrointestinal; HIV, human immunodeficiency virus positive; HTN, hypertension; IHD, ischemic heart disease; NM, not mentioned.

a

Supporting information Table S3.