Immune Persistence following Primary Immunization and the Immunogenicity and Safety of a Booster Dose of a Multidose Sabin Strain-Based Inactivated Polio Vaccine in Infants Aged 18 Months.

BACKGROUND: The multidose Sabin-strain inactivated poliovirus vaccine (sIPV) has the potential to significantly aid in the eradication of poliomyelitis, particularly in low- and middle-income countries. As part of a phase III clinical trial in which infants were given three doses of primary immunization at 2, 3, and 4 months of age, this study aimed to evaluate immune persistence following primary immunization, as well as the safety and immunogenicity of a booster of the 5-dose sIPV in infants aged 18 months. METHODS: Infants aged 18 months were given one booster dose of 5-dose sIPV in stage one, which was open-label. Unblinding was performed for stage two after completing primary immunization, which was randomized, blinded, and controlled; infants aged 18 months in the test group I-III, IPV group, and single-dose sIPV group were given one booster dose of 5-dose sIPV, conventional IPV, and single-dose sIPV, respectively, in stage two. RESULTS: This study included 1438 infants in the immune persistence and safety set and 1387 infants in the booster per-protocol set. Fourteen months after primary immunization, the seropositivity rates (≥1:8) for types 1-3 were 100%, 99.88%, and 99.53% in the 5-dose sIPV groups; 100%, 98.97%, and 97.23% in the IPV group; and 99.66%, 100%, and 99.66% in the single-dose sIPV group. A total of 30 days after booster immunization, the seropositivity rates (≥1:8) of 3 serotypes in all the groups reached 100%. The geometric mean titers of neutralizing antibodies for types 1-3 in the 5-dose sIPV group were 9962.89, 10273, and 7870.21, with geometric mean increases of 15.76, 33.15, and 24.5, compared to the pre-booster level. The overall incidence of adverse reactions was 8.97%, with fever being the most common, observed at rates of 7.1%, 5.52%, and 7.96% in the 5-dose sIPV, IPV, and single-dose groups, respectively (p = 0.4845). CONCLUSIONS: The 5-dose sIPV has shown promising immune persistence and robust immune response following a booster immunization, coupled with an acceptable safety profile.

Immunogenicity and safety of a live-attenuated varicella vaccine in a healthy population aged 13 years and older: A randomized, double-blind, controlled study.

OBJECTIVES: Vaccines for prevention against varicella are important for adolescents and adults, who have an increased risk of severe varicella. This study aimed to evaluate the immunogenicity and safety of a two-dose immunization schedule of a live-attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) in healthy adolescents and adults. METHODS: A randomized, double-blind, controlled clinical trial was conducted in healthy population aged ≥ 13 years old in China. Participants in block 1 were randomly assigned (1:1) to receive two doses of either the test vaccine or an active control vaccine, administered 4, 6 or 8 weeks apart. Participants in block 2 were randomly assigned (2:1) to receive two doses of test vaccine or placebo, administered 10 weeks apart. The primary immunogenicity endpoint was the seroconversion rates and GMTs of varicella zoster virus (VZV) antibodies measured by fluorescent-antibody-to-membrane-antigen (FAMA) 4 weeks post-immunization. The primary safety endpoint was the incidence of adverse reactions within 4 weeks after each dose. RESULTS: A total of 2398 participants were enrolled. The seroconversion rates of VZV antibodies were 79.55 % in the test group and 76.41 % in the active control group respectively 4 weeks after two doses of pooled schedule, with the difference of 3.14 % (95 %CI: -0.69 %, 6.97 %). The GMTs were 1:162.07 and 1:160.04 respectively, with the ratio of 1.013 (95 %CI: 0.910, 1.127). Both the seroconversion rates and GMTs reached the prespecified non-inferiority criteria. Two-dose schedule with an interval of 10 weeks could also induce high immune responses, with a seroconversion rate of 83.22 % and a GMT of 1:160.38 in the test group. Safety profiles were similar among the test group, active control group and placebo group. CONCLUSION: VarV, manufactured by Sinovac (Dalian), demonstrated higher immune response and better flexibility in the immunization schedule among heathy population aged 13 years and older, without increased safety risk.

Safety, immunogenicity, and lot-to-lot consistency of a multidose Sabin strain-based inactivated polio vaccine: a phase III, randomized, blinded, positive-control clinical trial in infants aged 2 months.

OBJECTIVES: To evaluate the safety, immunogenicity, and lot-to-lot consistency of Sabin strain-based inactivated polio vaccine (sIPV) in a five-dose vial presentation. METHODS: Stage I was an open-label safety observation, in which 72 healthy subjects (including 24 adults, children, and infants each) were given one or three doses of the five-dose vial sIPV; stage II was a randomized, blinded, and positive-control study, in which 1500 infants were randomized at the ratio of 1: 1: 1: 1: 1 into five groups to receive either three doses of the five-dose sIPV three lots, a conventional inactivated poliovirus vaccine, or a single-dose sIPV as controls, for primary immunization. Safety, immunogenicity, and lot-to-lot consistency were assessed. RESULTS: Among 1456 subjects who completed the primary immunization, the geometric mean titer ratios of types 1, 2, and 3 of each pair of lots were all within the equivalence criteria margin (0.67-1.50). The seroconversion rates of types 1, 2, and 3 in the combined test group were 98.02%, 94.07%, and 98.77%, respectively, which were noninferior to both control groups. The overall incidence of adverse reactions was 29.68% and erythema was the most common adverse reaction with incidences of 10.47%,9.33%, and 9.73% in the combined test group and control groups (P >0.05). CONCLUSION: The five-dose sIPV demonstrated good safety, immunogenicity, and lot-to-lot consistency.

Safety and Immunogenicity of an Inactivated COVID-19 Vaccine, WIBP-CorV, in Healthy Children: Interim Analysis of a Randomized, Double-Blind, Controlled, Phase 1/2 Trial.

Safe and effective vaccines against SARS-CoV-2 for children are urgently needed. Here we aimed to assess the safety and immunogenicity of an inactivated COVID-19 vaccine candidate, WIBP-CorV, in participants aged 3-17 years. A randomized, double-blind, placebo-controlled, phase 1/2 clinical trial was conducted in Henan Province, China, in healthy children aged 3-17 years. 240 participants in phase 1 trial and 576 participants in phase 2 trial were randomly assigned to vaccine or control with an age de-escalation in three cohorts (3-5, 6-12 and 13-17 years) and dose-escalation in three groups (2.5, 5.0 and 10.0µg/dose), and received 3 intramuscular injections at day 0, 28, and 56. WIBP-CorV showed a promising safety profile with approximately 17% adverse reactions within 30 days after injection and no grade 3 or worse adverse events. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting. The geometric mean titers of neutralizing antibody ranged from 102.2 to 1065.5 in vaccinated participants at 28 days after the third vaccination, and maintained at a range of 14.3 to 218.2 at day 180 after the third vaccination. WIBP-CorV elicited significantly higher titers of neutralizing antibody in the cohort aged 3-5 years than the other two cohorts. There were no detectable antibody responses in all alum-only groups. Taken together, our data demonstrate that WIBP-CorV is safe and well tolerated at all tested doses in participants aged 3-17 years, and elicited robust humoral responses against SARS-CoV-2 lasted for at least 6 months after the third vaccination. This study is ongoing and is registered with www.chictr.org.cn, ChiCTR2000031809.

Immunogenicity and safety of an egg culture-based quadrivalent inactivated non-adjuvanted subunit influenza vaccine in subjects ≥3 years: A randomized, multicenter, double-blind, active-controlled phase III, non-inferiority trial.

Subunit influenza vaccine only formulated with surface antigen proteins has better safety profiles relative to split-virion influenza vaccine. Compared to the traditional quadrivalent split-virion influenza vaccine, a novel quadrivalent subunit influenza vaccine is urgently needed in China. We completed a phase 3, randomized, double-blind, active-controlled, non-inferiority clinical study at two sites in Henan Province, China. Eligible volunteers were split into four age cohorts (3-8 years, 9-17 years, 18-64 years, and ≥ 65 years, based on their dates of birth) and randomly assigned (1:1) to the subunit and the split-virion ecNAIIV4 groups. All volunteers were intramuscularly administered a single vaccine dose at baseline, and children aged 3-8 years received a boosting dose at day 28. And the immune response was evaluated by measuring hemagglutinin-inhibition antibody titers against the four vaccine strains in blood samples. Safety profiles had nonsignificant differences between the study groups in ≥ 3 years cohort. Most adverse reactions post-vaccination, both local and systemic, were mild to moderate and resolved within 3 days. And no serious adverse events occurred. The immunogenicity of the trial vaccine was non-inferior to the comparator. Further, a two-dose vaccine series can provide better seroprotection than that of a one-dose series in children aged 3-8 years, with clinically acceptable safety profiles. Clinical Trials Registration. ChiCTR2100049934.

Immunogenicity and Safety of a Booster Dose of Live Attenuated Varicella Vaccine, and Immune Persistence of a Primary Dose for Children Aged 2 to 6 Years.

AIM: To evaluate the immunogenicity and safety of a booster dose of live attenuated varicella vaccine (VarV) manufactured by Sinovac (Dalian) Vaccine Technology Co. Ltd., and the immune persistence of a primary dose in 2- to 6-year-old children. METHODS: A phase IV, open-label study was conducted in China. Children previously vaccinated with a single dose of VarV at 1~3 years old received one dose of homologous VarV in the first year, the second year, or the third year after the primary immunization as booster immunization. Immune persistence was evaluated in an immune persistence analysis set, while immunogenicity was evaluated in a per-protocol analysis set, and safety was evaluated in a safety analysis set. The primary endpoint was the seropositive rate and the seroconversion rate of VarV antibody. The trial was registered at ClinicalTrials.gov (NCT02981836). RESULTS: From July 2018 to August 2020, a total of 849 vaccinated children received the booster vaccination of VarV, one booster dose for each child (301 vaccinated in the first year after primary immunization (Group 1), 276 vaccinated in the second year after primary immunization (Group 2), 272 vaccinated in the third year after primary immunization (Group 3)). The seropositive rates were 99.34%, 97.83%, and 98.16% in Groups 1-3, with GMTs of 1:22.56, 1:18.49, and 1:18.45, respectively. Thirty days after the vaccine booster dose, the seropositive rates of the three groups were all 100% and the seroconversion rates were 52.54%, 67.46%, and 66.67%, with GMTs of 1:68.49, 1:76.32 and 1:78.34, respectively. The seroconversion rates in Groups 2 and 3 were both higher than that in Group 1 (p = 0.0005 and p = 0.0008). The overall incidence of adverse reactions was 7.77%, with 7.64%, 8.33%, and 7.35% in Groups 1, 2, and 3, respectively. The main symptom among adverse reactions was fever, the incidence of which ranged from 5.07% to 6.64% in each group, and no vaccine-related serious adverse events occurred. CONCLUSIONS: VarV had good immune persistence in 1~3 years after primary immunization. A vaccine booster dose for children aged 1~3 years after primary immunization recalled specific immune response to varicella-zoster virus, with no safety concerns increased.

Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: a randomised, double-blind, controlled, phase 1/2 trial.

BACKGROUND: Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3-17 years. METHODS: A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3-5 years, 6-12 years, or 13-17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 µg, 4 µg, or 8 µg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing. FINDINGS: Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=72, 24 for each age cohort [3-5, 6-12, and 13-17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 µg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=180, 60 for each age cohort [3-5, 6-12, and 13-17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3-5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13-17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3-5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13-17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3-5 years cohort, 84·1 to 168·6 in the 6-12 years cohort, and 88·0 to 155·7 in the 13-17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3-5 years cohort, 127 to 184·8 in the 6-12 years cohort, and 150·7 to 199 in the 13-17 years cohort on day 28 after the third vaccination. INTERPRETATION: The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3-17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 µg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18 years or older: A randomized, double-blind, placebo-controlled, phase 1/2 trial.

BACKGROUND: We aimed to assess the safety and immunogenicity of an inactivated vaccine against COVID-19 in Chinese adults aged ≥18 years. METHODS: This is an ongoing randomized, double-blind, placebo-controlled, phase 1/2 clinical trial among healthy adults aged ≥18 years in Henan Province, China. Participants (n = 336 in 18-59 age group and n = 336 in ≥60 age group) were enrolled between April 12 and May 17 2020, and were equally randomized to receive vaccine or placebo (aluminum hydroxide adjuvant) in a three-dose schedule of 2·5, 5, or 10 µg on days 0, 28, and 56. Another 448 adults aged 18-59 years were equally allocated to four groups (a one-dose schedule of 10 µg, and two-dose schedules of 5 µg on days 0 and 14/21/28) and received vaccine or placebo (ratio 3:1 within each group). The primary outcomes were 7-day post-injection adverse reactions and neutralizing antibody titres on days 28 and 90 after the whole-course vaccination. Trial registration: www.chictr.org.cn #ChiCTR2000031809. FINDINGS: The 7-day adverse reactions occurred in 4·8% to 32·1% of the participants in various groups, and most adverse reactions were mild, transient, and self-limiting. Twenty participants reported 68 serious adverse events which were judged to be unrelated to the vaccine. The 90-day post-injection geometric mean titres of neutralizing antibody ranged between 87 (95% CI: 61-125) and 129 (99-169) for three-dose schedule among younger and older adults; 20 (14-27), 53 (38-75), and 44 (32-61) in 5 µg days 0 and 14/21/28 groups, respectively, and 7 (6-9) in one-dose 10 µg group. There were no detectable antibody responses in all placebo groups. INTERPRETATION: The inactivated vaccine against COVID-19 was well tolerated and immunogenic in both younger and older adults. The two-dose schedule of 5 µg on days 0 and 21/28 and three-dose schedules on days 0, 28, and 56 could be further evaluated for long-term safety and efficacy in the phase 3 trials.

Effect of 2 Inactivated SARS-CoV-2 Vaccines on Symptomatic COVID-19 Infection in Adults: A Randomized Clinical Trial.

Importance: Although effective vaccines against COVID-19 have been developed, additional vaccines are still needed. Objective: To evaluate the efficacy and adverse events of 2 inactivated COVID-19 vaccines. Design, Setting, and Participants: Prespecified interim analysis of an ongoing randomized, double-blind, phase 3 trial in the United Arab Emirates and Bahrain among adults 18 years and older without known history of COVID-19. Study enrollment began on July 16, 2020. Data sets used for the interim analysis of efficacy and adverse events were locked on December 20, 2020, and December 31, 2020, respectively. Interventions: Participants were randomized to receive 1 of 2 inactivated vaccines developed from SARS-CoV-2 WIV04 (5 µg/dose; n = 13 459) and HB02 (4 µg/dose; n = 13 465) strains or an aluminum hydroxide (alum)-only control (n = 13 458); they received 2 intramuscular injections 21 days apart. Main Outcomes and Measures: The primary outcome was efficacy against laboratory-confirmed symptomatic COVID-19 14 days following a second vaccine dose among participants who had no virologic evidence of SARS-CoV-2 infection at randomization. The secondary outcome was efficacy against severe COVID-19. Incidence of adverse events and reactions was collected among participants who received at least 1 dose. Results: Among 40 382 participants randomized to receive at least 1 dose of the 2 vaccines or alum-only control (mean age, 36.1 years; 32 261 [84.4%] men), 38 206 (94.6%) who received 2 doses, contributed at least 1 follow-up measure after day 14 following the second dose, and had negative reverse transcriptase-polymerase chain reaction test results at enrollment were included in the primary efficacy analysis. During a median (range) follow-up duration of 77 (1-121) days, symptomatic COVID-19 was identified in 26 participants in the WIV04 group (12.1 [95% CI, 8.3-17.8] per 1000 person-years), 21 in the HB02 group (9.8 [95% CI, 6.4-15.0] per 1000 person-years), and 95 in the alum-only group (44.7 [95% CI, 36.6-54.6] per 1000 person-years), resulting in a vaccine efficacy, compared with alum-only, of 72.8% (95% CI, 58.1%-82.4%) for WIV04 and 78.1% (95% CI, 64.8%-86.3%) for HB02 (P < .001 for both). Two severe cases of COVID-19 occurred in the alum-only group and none occurred in the vaccine groups. Adverse reactions 7 days after each injection occurred in 41.7% to 46.5% of participants in the 3 groups; serious adverse events were rare and similar in the 3 groups (WIV04: 64 [0.5%]; HB02: 59 [0.4%]; alum-only: 78 [0.6%]). Conclusions and Relevance: In this prespecified interim analysis of a randomized clinical trial, treatment of adults with either of 2 inactivated SARS-CoV-2 vaccines significantly reduced the risk of symptomatic COVID-19, and serious adverse events were rare. Data collection for final analysis is pending. Trial Registration: ClinicalTrials.gov Identifier: NCT04510207; Chinese Clinical Trial Registry: ChiCTR2000034780.

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial.

BACKGROUND: The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans. METHODS: We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18-80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18-59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 µg, 4 µg, or 8 µg on days 0 and 28. In phase 2, healthy adults (aged 18-59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 µg on day 0 or on a two-dose schedule of 4 µg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459. FINDINGS: In phase 1, 192 participants were enrolled (mean age 53·7 years [SD 15·6]) and were randomly assigned to receive vaccine (2 µg [n=24], 4 µg [n=24], or 8 µg [n=24] for both age groups [18-59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18-59 years, one [4%] in the 2 µg group, one [4%] in the 4 µg group, and two [8%] in the 8 µg group; ≥60 years, one [4%] in the 8 µg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18-59 years (87·7 [95% CI 64·9-118·6], 2 µg group; 211·2 [158·9-280·6], 4 µg group; and 228·7 [186·1-281·1], 8 µg group) and the group aged 60 years and older (80·7 [65·4-99·6], 2 µg group; 131·5 [108·2-159·7], 4 µg group; and 170·87 [133·0-219·5], 8 µg group) compared with the placebo group (2·0 [2·0-2·0]). In phase 2, 448 participants were enrolled (mean age 41·7 years [SD 9·9]) and were randomly assigned to receive the vaccine (8 µg on day 0 [n=84] or 4 µg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 µg day 0; 18 [21%], 4 µg days 0 and 14; 15 [18%], 4 µg days 0 and 21; and ten [12%], 4 µg days 0 and 28). One placebo recipient in the 4 µg days 0 and 21 group reported grade 3 fever, but was self-limited and recovered. All other adverse reactions were mild or moderate in severity. The most common systematic adverse reaction was fever (one [1%], 8 µg day 0; one [1%], 4 µg days 0 and 14; three [4%], 4 µg days 0 and 21; two [2%], 4 µg days 0 and 28). The vaccine-elicited neutralising antibody titres on day 28 were significantly greater in the 4 µg days 0 and 14 (169·5, 95% CI 132·2-217·1), days 0 and 21 (282·7, 221·2-361·4), and days 0 and 28 (218·0, 181·8-261·3) schedules than the 8 µg day 0 schedule (14·7, 11·6-18·8; all p<0·001). INTERPRETATION: The inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 µg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 µg dose or 4 µg dose on days 0 and 14. FUNDING: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.

Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials.

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed. Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China. Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 µg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 µg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]). Design, Setting, and Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020. Main Outcomes and Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups. Conclusions and Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.