Immunogenicity, safety, and immune persistence of a novel inactivated human enterovirus 71 vaccine: a phase II, Randomized, double-blind, placebo-controlled Trial.
BACKGROUND
Vaccination is considered a top priority for the control of human enterovirus 71 (EV71) infection outbreaks.


METHODS
On the basis of phase I trial results, we conducted a double-blind, randomized, controlled trial to evaluate the optimal dose, immunogenicity, safety and immune persistence of the vaccine. A total of 480 healthy infants were randomly assigned to receive 2 injections of 100 U of vaccine, 200 U of vaccine, 400 U of vaccine, or placebo. Solicited adverse events (AEs) within 7 days and unsolicited AEs within 28 days after each vaccination were collected for safety evaluation. Blood samples were collected for neutralizing antibody assay.


RESULTS
EV71 vaccine was well tolerated, and no dose-related safety concerns were observed. Two doses of the vaccine yielded seropositivity frequencies of 92.3%, 95.9%, and 99.0% (with titers ≥1:8) in the 100 U, 200 U, and 400 U groups, respectively. Geometric mean titers measured by neutralizing antibody assay increased to 60.2 (95% confidence interval [CI], 41.9-86.4), 72.8 (95% CI, 50.8-104.3), and 252.1 (95% CI, 180.8-351.6) for the 100 U, 200 U, and 400 U groups, respectively. The dose-response relationship, with the 400 U dose showing higher immunogenicity than the 100 U and 200 U doses, remained until 13 months after the second vaccination, despite waning antibody levels.


CONCLUSIONS
The 400 U dose was recommended as the optimal dose for the phase III trial because of its good safety profile and higher immunogenicity.
Center for Disease Control and Prevention of the Guangxi Zhuang Autonomous Region, Nanning.
Yan-Ping
YP
Li
Zheng-Lun
ZL
Liang
Jie-Lai
JL
Xia
Jun-Yu
JY
Wu
Ling
L
Wang
Li-Fei
LF
Song
Qun-Ying
QY
Mao
Shu-Qun
SQ
Wen
Ren-Guo
RG
Huang
Yuan-Sheng
YS
Hu
Xin
X
Yao
Xu
X
Miao
Xing
X
Wu
Rong-Cheng
RC
Li
Jun-Zhi
JZ
Wang
Wei-Dong
WD
Yin
D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D002675:Child, Preschool; D004311:Double-Blind Method; D029821:Enterovirus A, Human / Q000276:immunology*; D005260:Female; D006801:Humans; D007156:Immunologic Memory / Q000276:immunology; D007223:Infant; D008297:Male; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D015164:Vaccines, Inactivated; D014765:Viral Vaccines
EV71 vaccine; immune persistence; immunogenicity; safety