Introduction
Methods
Search strategy
Eligibility criteria
Study selection
Data extraction
Risk of bias assessment
Data analysis
Results
Study selection and study characteristics
Study | Clinical trials registration | Vaccine types | Study design | Country/ region | Study period | Age | No. of participants | Controls | Outcomes |
---|---|---|---|---|---|---|---|---|---|
Walsh et al., 2023 | NCT05035212 | RSVpreF (Subunit vaccine) | Phase III, randomized, double-blind, multicenter, placebo-controlled study | Argentina, Canada, Finland, Japan, the Netherlands, South Africa, and the United States | August 31, 2021-July 14, 2022 | ≥ 60 years | 34,284 | 17,069 | Efficacy and safety |
Papi et al., 2023 | NCT04886596 | RSVPreF3 OA (Subunit vaccine) | Phase III, randomized, observer-blind, placebo-controlled, multi-country study | Australia, Belgium, Canada, Estonia, Finland, Germany, Italy, Japan, Korea, Mexico, New Zealand, Poland, Russian Federation, South Africa, Spain, United Kingdom, and the United States | May 25, 2021-January 31, 2022 | ≥ 60 years | 24,966 | 12,499 | Efficacy and safety |
Leroux-Roels et al., 2023 | NCT03814590 | RSVPreF3 (Subunit vaccine) | Phase I/II, randomized, observer-blind, placebo-controlled study | Belgium and the United States | January 21, 2019-February 23, 2021 | 18–40 years;60–80 years | 1049 | 112 | Safety and Immunogenicity |
Kotb et al., 2023 | NCT04090658 | RSVPreF3/AS01B (Subunit vaccine) | Phase I, randomized, observer-blind, placebo-controlled study | Japan | September 2019-December 2020 | 60–80 years | 40 | 20 | Safety and Immunogenicity |
Kampmann et al., 2023 | NCT04424316 | RSVpreF (Subunit vaccine) | Phase III, randomized, double-blind, placebo-controlled study | Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, Gambia, Japan, Korea, Mexico, Netherlands, New Zealand, Philippines, South Africa, Spain, Taiwan, the United States | June 17, 2020-November 24, 2023 | 18–49 years, 24–36 weeks’ gestation | 7358 | 3676 | Efficacy and safety |
Falsey et al., 2023 | NCT03982199 | Ad26.RSV.preF-RSV preF (Mixed adenovirus and subunit vaccine) | Phase IIb, randomized, double-blind, placebo-controlled, proofof-concept study | The United States | August 5, 2019-November 13, 2019 | ≥ 65 years | 5782 | 2891 | Efficacy, safety and Immunogenicity |
Comeaux et al., 2023 | NCT03502707 | Ad26.RSV.preF (Adenovirus vaccine) | Phase I/IIa, randomized, double-blind, placebo-controlled study | The United States | July 9, 2018-June 30, 2022 | ≥ 60 years | 352 | 40 | Safety and Immunogenicity |
Bebia et al., 2023 | NCT04126213 | RSVPreF3 (Subunit vaccine) | Phase II, randomized, observer-blind, placebo-controlled study | Australia, Canada, Finland, France, New Zealand, Panama, South Africa, Spain, and the United States | November 5, 2019-May 14, 2021 | 18–40 years, pregnant women | 211 | 66 | Safety and Immunogenicity |
Walsh et al., 2022 | NCT03529773 | RSVpreF (Subunit vaccine) | Phase I/II randomized, observer-blind, placebo-controlled, dose-finding study | The United States | April 2018-November 2019 | 18–49 years; 50–85 years | 1208 | 104 | Safety and Immunogenicity |
Stuart et al., 2022 | NCT03303625 | Ad26.RSV.preF (Adenovirus vaccine) | Phase I/IIa, randomized, double-blind, placebo-controlled study | Finland the United Kingdom, and the United States | November 29, 2019-April 21, 2020 | 18–50 years; 1–2 years | 48 | 16 | Safety and Immunogenicity |
Simões et al., 2022 | NCT04032093 | RSVpreF (Subunit vaccine) | Phase IIb, randomized, observer-blind, placebo-controlled, multicountry, proof-of-concept study | Chile, Argentina South Africa, and the United States | July 7, 2019-September 30, 2021 | 18–49 years, 24–36 weeks’ gestation | 403 | 79 | Efficacy, safety and Immunogenicity |
Schwarz et al., 2022 | NCT03674177 | RSVPreF3 (Subunit vaccine) | Phase I/II, randomized, observer-blind, placebo-controlled, first-in-human study | Finland Germany, and the United States | October 2018-September 2019 | 18–45 years, non-pregnant women | 501 | 126 | Safety and Immunogenicity |
Schmoele et al., 2022 | NCT04785612 | RSVpreF (Subunit vaccine) | Phase IIa, randomized, double-blind, single-center, exploratory study | Chile, Argentina South Africa, and the United States | November 10, 2020-April 8, 2021 | 18–49, 24–36 weeks’ gestation | 70 | 35 | Efficacy, safety and Immunogenicity |
Sadoff et al., 2022 | NCT03334695 | Ad26.RSV.preF (Adenovirus vaccine) | Phase IIa, randomized, double-blind, placebo-controlled study | The United Kingdom | August 2, 2017-November 27, 2018 | 18–50 years | 63 | 32 | Efficacy, safety and Immunogenicity |
Peterson et al., 2022 | NCT04071158 | RSVpreF (Subunit vaccine) | Phase Iib, randomized, observer-blind, placebo-controlled, multicenter study | The United States | October-December, 2019 | 18–45 years, non-pregnant women | 709 | 141 | Safety and Immunogenicity |
Baber et al., 2022 | NCT03572062 | RSVpreF (Subunit vaccine) | Phase I/II, randomized, observer-blind, placebo-controlled, dose-finding study | Australia | April 29, 2019-August 19, 2020 | 65–85 years | 317 | / | Safety and Immunogenicity |
Sadoff et al., 2021 | NCT03339713 | Ad26.RSV.preF (Adenovirus vaccine) | Phase IIa, randomized, double-blind, placebo-controlled, parallel-group study | The United States | December 7, 2017-July 23, 2018 | ≥ 60 years | 180 | 90 | Safety and Immunogenicity |
Aliprantis et al., 2021 | / | mRNA-1777 (mRNA vaccine) | Phase I, randomized, partially double-blind, placebo-controlled, first-in-human, dose-escalation study | Australia | November 2016-May 2019 | 18–49 years | 242 | 45 | Safety and Immunogenicity |
Williams et al., 2020 | NCT02926430 | Ad26.RSV.preF (Adenovirus vaccine) | Phase I, randomized, double-blind, placebo-controlled study | The United States | November 8, 2016-May 14, 2018 | ≥ 60 years | 73 | 24 | Safety and Immunogenicity |
Schwarz et al., 2019 | NCT02956837 | RSV-PreF (Subunit vaccine) | Phase II, randomized, observer-blind, multicenter study | Belgium, Estonia, France, and Germany | November 2016-February 2018 | 18–45 years | 406 | 102 | Safety and Immunogenicity |
Beran et al., 2018 | NCT02360475/NCT02753413 | RSV-PreF (Subunit vaccine) | Randomized, observer-blinded, controlled study | Australia, the Czech Republic Germany, and the United States, | March 2015-June 2016 | 18–45 years, non-pregnant women | 600 | 175 | Safety and Immunogenicity |
Langley et al., 2017 | NCT01905215 | RSV-PreF (Subunit vaccine) | Phase I, randomized, observer-blind, controlled, first in-humans study | Canada | July 22, 2013-March 16, 2015 | 18–44 year, men | 128 | 33 | Safety and Immunogenicity |
Risk of bias assessment of included studies
Efficacy of RSV prefusion vaccine
Immunogenicity of RSV prefusion vaccine
Study | Vaccine types | Immunoassay days | RSV-A nAb GMFI | RSV-B nAb GMFI | RSV pre-F binding antibodies | RSV post-F binding antibodies | T cell response* |
---|---|---|---|---|---|---|---|
Papi et al., 2023 | RSVPreF3 OA (Subunit vaccine) | D31 | 10.2 | 8.5 | 13 | / | / |
Leroux-Roels et al., 2023 | RSVPreF3 (Subunit vaccine) | D31 | 5.6–13.7 | 9.2–10 | 7.2–13.5 | / | / |
Kotb et al., 2023 | RSVPreF3/AS01B (Subunit vaccine) | D30 | 7.3 | 8.4 | 12.8 | / | / |
Falsey et al., 2023 | Ad26.RSV.preF-RSV preF (Mixed adenovirus and subunit vaccine) | D15 | 12.1 | 9.4 | 8.6 | / | 13 |
Comeaux et al., 2023 | Ad26.RSV.preF (Adenovirus vaccine) | D29 | 2.7–10.5 | / | 2.1–13.8 | / | 2.8–9.7 |
Bebia et al., 2023 | RSVPreF3 (Subunit vaccine) | D31 | 12.7–14.9 | 10.6–13.2 | 13.4–17.7 | / | / |
Walsh et al., 2022 | RSVpreF (Subunit vaccine) | D31 | 10.6–16.9 | 10.3–19.8 | 16.4–30.6 | / | / |
Stuart et al., 2022 | Ad26.RSV.preF (Adenovirus vaccine) | D29 | 13.3 | 27.9 | 19.9 | 8.9 | / |
Simões et al., 2022 | RSVpreF (Subunit vaccine) | / | 11.0-15.1 | 13.7–17.5 | / | / | / |
Schwarz et al., 2022 | RSVPreF3 (Subunit vaccine) | D31 | 6.26–7.95 | / | 6.8–14.0 | / | / |
Schmoele et al., 2022 | RSVpreF (Subunit vaccine) | D28 | 20.5 | 20.3 | / | / | / |
Sadoff et al., 2022 | Ad26.RSV.preF (Adenovirus vaccine) | D28 | 5.8 | / | 6.8 | 4.2 | / |
Peterson et al., 2022 | RSVpreF (Subunit vaccine) | D31 | 14.1 | 14.6 | / | / | / |
Baber et al., 2022 | RSVpreF (Subunit vaccine) | D31 | 4.8–11.6 | 4.5–14.1 | 6.4–14.3 | / | 1.1–1.8 |
Sadoff et al., 2021 | Ad26.RSV.preF (Adenovirus vaccine) | D28 | 2.8–3.1 | / | 2.3–2.6 | 2.0-2.1 | / |
Aliprantis et al., 2021 | mRNA-1777 (mRNA vaccine) | D29 | 2.5–4.3 | / | 1.7–4.5 | / | 2.2–3.7 |
Williams et al., 2020 | Ad26.RSV.preF (Adenovirus vaccine) | D29 | 1.6–2.1 | 1.7-2.0 | 1.5–1.7 | / | 2.1–2.4 |
Schwarz et al., 2019 | RSV-PreF (Subunit vaccine) | D30 | 3.75–4.36 | 2.36–2.76 | 5.86–6.74 | / | / |
Beran et al., 2018 | RSV-PreF (Subunit vaccine) | D30 | 3.1–3.9 | / | 25.7–38.2 | / | / |
Langley et al., 2017 | RSV-PreF (Subunit vaccine) | D30 | 1.28–2.92 | 1.40–2.23 | 2.5–4.2 | / | / |
Safety of RSV prefusion vaccine
Adverse events | Vaccine type | No. of studies | Reaction/total | RR (95%CI) | Heterogeneity I2 (%) | Test of effect size (p value) | |
---|---|---|---|---|---|---|---|
Vaccination | Control | ||||||
Local adverse events (any) | Overall | 11 | 1239/5067 | 365/4363 | 3.43 [2.38, 4.96] | 83 | < 0.00001 |
Subunit vaccine | 4 | 614/4000 | 262/3671 | 2.97 [1.47, 6.00] | 77 | 0.002 | |
Adenovirus vaccine | 5 | 362/585 | 67/300 | 3.15 [1.95, 5.10] | 62 | < 0.00001 | |
Mixed adenovirus and subunit vaccine | 1 | 132/348 | 29/347 | 4.54 [3.12, 6.59] | / | < 0.00001 | |
mRNA vaccine | 1 | 131/134 | 7/45 | 6.28 [3.18, 12.42] | / | < 0.00001 | |
Systemic adverse events (any) | Overall | 11 | 1814/5067 | 1136/4353 | 1.68 [1.25, 2.26] | 90 | 0.0005 |
Subunit vaccine | 4 | 1242/4000 | 981/3671 | 1.24 [0.95, 1.63] | 74 | 0.12 | |
Adenovirus vaccine | 5 | 328/585 | 82/290 | 1.65 [1.08, 2.50] | 75 | 0.02 | |
Mixed adenovirus and subunit vaccine | 1 | 144/348 | 57/347 | 2.52 [1.93, 3.29] | / | < 0.00001 | |
mRNA vaccine | 1 | 100/134 | 16/45 | 2.10 [1.40, 3.15] | / | 0.0003 | |
Injection site pain | Overall | 22 | 4917/12,817 | 957/9621 | 3.72 [2.42, 5.74] | 97 | < 0.00001 |
Subunit vaccine | 15 | 4317/11,804 | 871/8939 | 3.32 [1.94, 5.69] | 98 | < 0.0001 | |
Adenovirus vaccine | 5 | 359/585 | 61/290 | 3.44 [2.41, 4.91] | 25 | < 0.00001 | |
Mixed adenovirus and subunit vaccine | 1 | 120/348 | 24/347 | 4.99 [3.30, 7.53] | / | < 0.00001 | |
mRNA vaccine | 1 | 121/134 | 1/45 | 40.63 [5.85, 282.44] | / | 0.0002 | |
Redness | Overall | 22 | 748/12,871 | 97/9621 | 4.48 [3.23, 6.20] | 24 | < 0.00001 |
Subunit vaccine | 13 | 677/11,804 | 86/8939 | 4.77 [3.08, 7.38] | 41 | < 0.00001 | |
Adenovirus vaccine | 5 | 17/585 | 1/290 | 3.65 [0.97, 13.72] | 0 | 0.05 | |
Mixed adenovirus and subunit vaccine | 1 | 22/348 | 7/347 | 3.13 [1.36, 7.24] | / | 0.008 | |
mRNA vaccine | 1 | 32/134 | 3/45 | 3.58 [1.15, 11.14] | / | 0.03 | |
Swelling | Overall | 21 | 672/12,836 | 108/9588 | 3.01 [1.95, 4.65] | 62 | < 0.00001 |
Subunit vaccine | 12 | 555/11,769 | 80/8906 | 4.17 [2.52, 6.92] | 52 | < 0.00001 | |
Adenovirus vaccine | 5 | 96/585 | 18/290 | 2.28 [0.87, 6.00] | 64 | 0.09 | |
Mixed adenovirus and subunit vaccine | 1 | 12/348 | 6/347 | 1.99 [0.76, 5.25] | / | 0.16 | |
mRNA vaccine | 1 | 9/134 | 4/45 | 0.76 [0.24, 2.34] | / | 0.63 | |
Fatigue | Overall | 22 | 4395/12,871 | 2640/9625 | 1.45 [1.25, 1.69] | 84 | < 0.00001 |
Subunit vaccine | 13 | 3993/11,804 | 2536/8943 | 1.25 [1.09, 1.43] | 79 | 0.001 | |
Adenovirus vaccine | 5 | 240/585 | 52/290 | 2.11 [1.28, 3.48] | 66 | 0.004 | |
Mixed adenovirus and subunit vaccine | 1 | 96/348 | 42/347 | 2.28 [1.64, 3.17] | / | < 0.00001 | |
mRNA vaccine | 1 | 66/134 | 10/45 | 2.22 [1.25, 3.93] | / | 0.006 | |
Headache | Overall | 22 | 3419/12,871 | 1873/9625 | 1.55 [1.32, 1.81] | 79 | < 0.00001 |
Subunit vaccine | 13 | 3085/11,804 | 1787/8943 | 1.36 [1.18, 1.57] | 72 | < 0.0001 | |
Adenovirus vaccine | 5 | 200/585 | 48/290 | 1.93 [1.22, 3.05] | 59 | 0.005 | |
Mixed adenovirus and subunit vaccine | 1 | 83/348 | 29/347 | 2.85 [1.92, 4.24] | / | < 0.00001 | |
mRNA vaccine | 1 | 51/134 | 8/45 | 1.90 [1.02, 3.55] | / | 0.04 | |
Myalgia | Overall | 18 | 2649/11,737 | 1123/9240 | 2.32 [1.80, 2.98] | 85 | < 0.00001 |
Subunit vaccine | 11 | 2279/10,670 | 1057/8558 | 1.85 [1.42, 2.42] | 85 | < 0.00001 | |
Adenovirus vaccine | 5 | 216/585 | 31/290 | 3.96 [2.35, 6.66] | 29 | < 0.00001 | |
Mixed adenovirus and subunit vaccine | 1 | 95/348 | 30/347 | 3.16 [2.15, 4.63] | / | < 0.00001 | |
mRNA vaccine | 1 | 59/134 | 5/45 | 3.96 [1.70, 9.25] | / | 0.001 | |
Arthralgia | Overall | 16 | 1373/11,244 | 759/8827 | 1.93 [1.40, 2.66] | 81 | < 0.0001 |
Subunit vaccine | 10 | 1209/10,525 | 739/8492 | 1.51 [1.11, 2.06] | 80 | 0.009 | |
Adenovirus vaccine | 5 | 137/585 | 18/290 | 3.43 [1.44, 8.16] | 60 | 0.005 | |
mRNA vaccine | 1 | 27/134 | 2/45 | 4.53 [1.12, 18.31] | / | 0.03 | |
Nausea | Overall | 15 | 1260/9901 | 915/8230 | 1.39 [1.02, 1.88] | 73 | 0.04 |
Subunit vaccine | 8 | 1127/8834 | 895/7548 | 0.99 [0.82, 1.21] | 46 | 0.95 | |
Adenovirus vaccine | 5 | 83/585 | 9/290 | 3.74 [0.83, 16.90] | 75 | 0.09 | |
Mixed adenovirus and subunit vaccine | 1 | 31/348 | 7/347 | 4.42 [1.97, 9.89] | / | 0.0003 | |
mRNA vaccine | 1 | 19/134 | 4/45 | 1.60 [0.57, 4.44] | / | 0.37 | |
Chill | Overall | 8 | 271/1676 | 21/467 | 4.21 [2.06, 8.62] | 55 | < 0.0001 |
Subunit vaccine | 2 | 94/957 | 4/132 | 3.10 [1.22, 7.84] | 0 | 0.02 | |
Adenovirus vaccine | 5 | 159/585 | 12/290 | 7.37 [4.20, 12.94] | 0 | < 0.00001 | |
mRNA vaccine | 1 | 18/134 | 5/45 | 1.21 [0.48, 3.07] | / | 0.69 | |
≥Grade 3 | Overall | 20 | 423/9210 | 54/5971 | 3.06 [1.91, 4.91] | 49 | < 0.00001 |
Subunit vaccine | 13 | 293/8132 | 48/5289 | 2.11 [1.41, 3.15] | 25 | 0.0003 | |
Adenovirus vaccine | 5 | 79/585 | 2/290 | 7.24 [1.60, 32.65] | 47 | 0.01 | |
Mixed adenovirus and subunit vaccine | 1 | 21/348 | 4/347 | 5.23 [1.82, 15.09] | / | 0.002 | |
mRNA vaccine | 1 | 30/134 | 0/45 | 20.79 [1.30, 333.14] | / | 0.03 |