The Journal of Infectious Diseases

MAJOR ARTICLE

Immunogenicity and Safety of a Sabin Strain–Based

Inactivated Polio Vaccine: A Phase 3 Clinical Trial
Yuemei Hu,1,a Jianfeng Wang,3,a Gang Zeng,4,a Kai Chu,1 Deyu Jiang,5 Fengdong Zhu,7 Zhifang Ying,3 Lei Chen,8 Changgui Li,3,b Fengcai Zhu,2,b and
Weidong Yin6,b
1
Department of Vaccine Evaluation and 2Office of the Deputy Director, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, 3Division of Respiratory Virus Vaccines, National
Institute for Food and Drug Control, and 4Department of Clinical Research, 5Center of Research and Development, and 6Office of the General Manager, Sinovac Biotech, Beijing, 7Guanyun County
Center for Disease Control and Prevention, Guanyun, and 8Pizhou County Center for Disease Control and Prevention, Pizhou, China

(See the Editorial commentary by Sutter and Cochi, on pages 1545–6.)

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Background. The Sabin strain–based inactivated polio vaccine (sIPV) plays a vital role in eradicating poliomyelitis in devel-
oping countries.
Methods. The study was designed as a randomized, controlled, double-blinded, noninferiority trial. A total of 1200 healthy
infants aged 60–90 days were enrolled and randomly assigned to receive 3 doses of either sIPV (the experimental arm) or IPV (the
control arm) at days 0, 30, and 60. Immunogenicity and safety outcomes were assessed using the per-protocol and safety populations,
respectively.
Results. A total of 553 and 562 participants in the sIPV and IPV groups, respectively, were included in the per-protocol popula-
tion. Seroconversion rates in the sIPV and IPV groups were 98.0% and 94.1%, respectively, for type 1 poliovirus (P < .01); 94.8% and
84.0%, respectively, for type 2 (P < .01); and 98.9% and 97.7%, respectively, for type 3 (P = .11). A total of 599 and 600 participants in
the sIPV and IPV groups, respectively, were included in the safety population. Fever was the most common adverse event, occurring
in 61.6% and 49.8% of participants in the experimental and control arms, respectively (P < .01).
Conclusions. The sIPV demonstrated an immunogenicity profile noninferior to that of the conventional IPV and had a good
safety profile.
Clinical Trials Registration. NCT03526978.
Keywords. Poliovirus; inactivated vaccine; Sabin strain; phase 3 trial.

Poliomyelitis (polio) is a highly infectious disease caused by po- Polio vaccine, given multiple times, can protect a child for
liovirus and mainly affects children <5 years old [1]. The virus life [3]. There are 2 types of vaccines developed to stop polio
can invade the nervous system of young children and lead to irre- transmission: oral polio vaccine (OPV) and inactivated polio
versible paralysis in 1 of every 200 infections [2]. Currently, polio vaccine (IPV) [3, 9]. OPV and IPV have distinct advantages
has no cure but can be effectively prevented by vaccines [3]. Since and are both necessary to eliminate polio. On the one hand,
1988, when the Global Polio Eradication Initiative was launched, OPV is extremely effective in protecting both the individual
the number of polio cases worldwide has decreased by >99%, and the community from infecting wild polioviruses (WPVs);
from an estimated 350 000 cases in 1988 to 22 reported cases in however, because OPV is composed of a live attenuated vac-
2017 [2, 4]. However, as long as a single child remains infected, cine virus, it may result in vaccine-derived poliovirus (VDPV)
all children in the world are at risk of contracting poliovirus [5]. emergence or vaccine-associated paralytic polio (VAPP) on rare
China, the largest developing country in the world, was declared occasions [10–13]. On the other hand, IPV carries no risk of
as polio free in 2000 [6]. But the country is still highly vulnerable VDPV emergence or VAPP because it contains no live virus,
to the disease because two of its neighboring countries, Pakistan but IPV cannot stop the spread of poliovirus in a community,
and Afghanistan, remain polio endemic [5, 7, 8]. because when a person immunized with IPV is infected with
WPV, the virus may still replicate in the gut and could spread
to infect others [14–16]. Based on these features, the World
Received 18 October 2018; editorial decision 3 December 2018; accepted 29 March 2019;
published online April 8, 2019. Health Organization (WHO) has suggested that OPV must be
a
Y. H., J. W., and G. Z. contributed equally to this report. withdrawn soon after the end of WPV transmission, to prevent
b
C. L., F. Z., and W. Y. contributed equally to this report.
Correspondence: C. Li, Division of Respiratory Virus Vaccines, National Institute for Food and
VAPP emergence and VDPV, and that, during the interim, IPV
Drug Control, No. 2 Tiantan Xili, Beijing, China, 100050 (changguili@aliyun.com). should be used to maintain population immunity levels, to sus-
The Journal of Infectious Diseases®  2019;220:1551–7 tain a polio-free world [16, 17].
© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society
of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Compared with OPV, the manufacture of conventional
DOI: 10.1093/infdis/jiy736 IPV requires a much higher standard for biosafety and other

Immunogenicity and Safety of a Sabin IPV • jid 2019:220 (15 November) • 1551
containment requirements, mainly because IPV uses virulent random numbers generated by SAS 9.4 software (SAS Institute,
poliovirus strains as raw material [15]. These strict requirements Cary, NC), based on a preset block size, by independent bio-
substantially limit the number of manufacturers producing IPV, statisticians. When recruited into the study, every participant
especially in middle- and low-income countries [10, 15]. To end was assigned a unique random number identical to that labeling
vaccine-associated and vaccine-derived polio in resource-limited the vaccine to which they were assigned to receive. The study
areas, the WHO encourages the development new IPVs that use designers, data analysts, data managers, and safety assessors
less virulent strains, such as the Sabin strain–based inactivated were all blinded until the completion of the primary vaccina-
polio vaccine (sIPV), which carries a lower biosafety risk and tion course, the end of the 90-day safety observation period,
demonstrates a long-term affordability and accessibility [18]. The and measurement of neutralizing antibody levels.
aim of this study was to report immunogenicity and safety find-
ings from a phase 3 clinical trial of a new sIPV developed in China. Procedures
All participants were scheduled to receive 3 doses of either sIPV
METHODS or IPV as primary vaccine 0, 30, and 60 days after enrollment.
A booster dose would be provided to each participant at age
Vaccines

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18 months.
The studied sIPV, developed by Sinovac Biotech, is a liquid tri-
After each injection, the safety of the vaccine was assessed
valent vaccine (0.5 mL/dose) for intramuscular injection. It was
for 30 days. First, immediate complaints occurring ≤30 min-
generated from Sabin poliovirus type 1, 2, and 3 strains grown
utes after injection were recorded by physicians. Second, solic-
on Vero cells. Based on results of the phase 1 and 2 clinical tri-
ited and unsolicited adverse events occurring ≤7 days after
als of the sIPV, the antigen contents were determined to be 15,
injection were recorded by safety assessors via face-to-face or
45, and 45 D antigen units for type 1, 2, and 3 Sabin poliovi-
telephone-based interviews of guardians. Third, guardians
ruses, respectively [19]. The vaccines were prepared in a good
self-reported adverse events occurring 8–30 after injection.
manufacturing practice–accredited facility and were approved
Finally, safety assessors performed a follow-up interview of
by the National Institute for Food and Drug Control (NIFDC)
guardians on day 30 to review the safety record for each partic-
of China. The control IPV (0.5 mL/dose) was produced by
ipant. Solicited local adverse reactions included pain, redness,
Sanofi Pasteur. Type 1 (Mahoney strain), 2 (MEF-1 strain), and
swelling, nodules, and rash at the injection site. Solicited sys-
3 (Saukett strain) polioviruses grown on Vero cells were used to
temic adverse events were irritability, drowsiness, nausea, vom-
generate the control vaccine, with antigen contents of 40, 8, and
iting, diarrhea, and fever. Data on serious adverse events (SAEs)
32 D antigen units, respectively.
were collected throughout the trial.
A blood sample (volume, 3.0 mL) was collected from each
Study Design and Participants
participant on days 0 and 90 after the first injection of primary
The study was designed as a randomized controlled, dou-
vaccine. To assess the immunogenicity of the vaccines, the titers
ble-blinded, noninferiority trial and conducted in Pizhou City
of poliovirus 1–, 2–, and 3–specific neutralizing antibodies were
and Guanyun County in Jiangsu Province, China, from August
measured via the microneutralization assay. Seroconversion
2017 to January 2018. ​ It was implemented by the Jiangsu
was defined as a positive status (ie, a titer of 1:8 or higher) in
Provincial Center for Disease Control and Prevention (CDC)
seronegative subjects (whose baseline titer was below 1:8) or as
and by the local CDCs in Pizhou and Guanyun County. Sinovac
a 4-fold increase in titer in seropositive subjects (whose baseline
Biotech was responsible for monitoring the trial. Eligible study
titer was 1:8 or higher) after the primary vaccination.
participants were healthy infants aged 60–90 days who were legal
residents of the study sites at the time of the study. Those who Outcomes
(1) received polio vaccine previously, (2) had an axillary tem- The primary outcome of the study was the seroconversion rate
perature >37°C before vaccination, (3) had a history of allergy, of neutralizing antibodies against poliovirus 1, 2, and 3 on day
(4) had acute disease ≤7 days before enrollment, and/or (5) had 30 after completing the primary vaccination series. The sec-
any known immunodeficiency were excluded from the study. ondary outcome was the geometric mean titer (GMT) of neu-
Written informed consent was obtained from the legal guard- tralizing antibodies against poliovirus 1, 2, and 3 30 days after
ians of each infant before data collection and vaccination. The completing the primary vaccination series. Additionally, solic-
trial was registered at ClinicalTrials.gov (NCT03526978) and ited local and systemic adverse events, as well as SAEs, were also
approved by the Institutional Review Board of the Jiangsu CDC. assessed and compared between the 2 groups.

Randomization and Masking Laboratory Testing

After enrollment, each participant was randomly assigned A WHO-recommended microneutralization assay, using Sabin
to the sIPV arm or the IPV arm at a ratio of 1:1. The experi- strains to measure the titer of anti–poliovirus neutralizing anti-
mental and control vaccines were first masked and labeled with bodies, was performed by the NIFDC [20]. Before shipment

1552 • jid 2019:220 (15 November) • Hu et al

to the NIFDC, serum specimens were separated, frozen, and and 600 in the IPV group received at least 1 dose of primary
stored at the study site at −20°C, after coagulation. vaccine and were included in the safety population. There were
599, 585, and 578 participants in the sIPV group and 600, 592,
Statistical Analyses and 589 participants in the IPV group who received 1, 2, and
The sample size of the study was calculated by NCSS-PASS 3 doses of primary vaccine, respectively. The withdrawal rates
Software (NCSS, Kaysville, UT). We assumed that (1) the sero- were not significantly different between the 2 arms (P = .10).
conversion rate among recipients of the control vaccine was Meanwhile, 553 and 562 participants were included in the
90%, (2) the noninferiority margin was 9%, (3) the 1-tailed α per-protocol population after excluding those satisfying at least
level was 0.025, (4) the β level was 0.2 with a statistical power of 1 of the following criteria: (1) inability or refusal to have a blood
93.3% (ie, 1 − [β/3]) for each poliovirus type, (5) the withdrawal specimen collected after primary vaccination, (2) no vaccina-
rate of participants was no more than 20%, and (6) the number tion or blood specimen collected within the required time, and
of participants in each arm was equal. In addition, the guide- (3) receipt of protocol-prohibited vaccines (Figure 1). No sig-
lines for a phase 3 clinical trial issued by the China Food and nificant differences in age, sex, height, or weight were observed
Drug Administration was considered, which resulted in a total between the 2 groups in both the safety and per-protocol pop-

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sample size of 1200 infants, with 600 in each arm. ulations (Table 1).
The per-protocol population, including participants complet-
ing the study without major protocol deviation, was used for Immunogenicity
the immunogenicity analysis [20]. First, the seroconversion rate At the time of enrollment, the proportions of seropositive par-
was calculated, and its 95% confidence interval (CI) was gener- ticipants were statistically similar between the sIPV and IPV
ated using the Clopper-Pearson method. The Pearson χ2 test or arms (Table 1). For the per-protocol population, all partici-
the Fisher exact test was adopted to compare the difference in pants in the sIPV group (n = 553) and the IPV group (n = 562)
the seroconversion rates between the 2 study groups. Second, the developed neutralizing antibodies against poliovirus types 1, 2,
GMTs and fold increases after the primary vaccination were cal- and 3. The seroconversion rates in the sIPV and IPV groups
culated, and the Student t test was used to explore the difference were 98.0% and 94.1%, respectively, against type 1 poliovirus
between the 2 study groups after a log transformation of GMTs. (P < .01); 94.8% and 84.0%, respectively, against type 2 (P < .01);
In addition, to evaluate the effect of maternal antibodies on the and 98.9% and 97.7%, respectively, against type 3 (P = .11).
immunogenicity of the vaccines, an adjustment of the baseline Therefore, noninferiority of the immunogenicity of sIPV versus
GMTs for seropositive subjects was performed by diving the base- that of the IPV for all 3 poliovirus serotypes was established.
line GMTs by 2n, where n represented the number of days between Moreover, seroconversion rates against types 1 and 2 were sig-
collection of the 2 blood specimens 0 and 90 days after the first nificantly higher in the sIPV arm than in the IPV arm. Among
injection of primary vaccine. Seroconversion rates and increases the participants who were seronegative before vaccination, the
in GMTs were recalculated using the adjusted baseline GMTs. seroconversion rates against the 3 types of polioviruses in the
The safety population, including participants who received 2 groups were all 100%. In addition, after adjustment for the
at least 1 dose of primary vaccine and had corresponding safety influence of maternal antibodies on the immunogenicity of the
records, was used for the safety analysis [21]. The safety profiles vaccines, the seroconversion rates in the sIPV and IPV groups
were first coded and categorized using the MedDRA Software were 99.5% and 99.3%, respectively, against type 1 poliovirus
(MedDRA MSSO, McLean, VA). The number of episodes, fre- (P = .72); 98.6% and 97.0%, respectively, against type 2 (P = .08);
quencies, and proportions were calculated to describe the char- and 99.6% and 99.6%, respectively, against type 3 (P = .99). All
acteristics of the adverse events of interest. The difference in the adjusted seroconversion rates were higher than unadjusted
frequency of each adverse event between the 2 groups was eval- seroconversion rates (Table 2).
uated via the Fisher exact test. Before the initial injection, the GMTs of antibodies against
Demographic characteristics at baseline, such as sex, age, poliovirus types 1, 2, and 3 were distributed equally between
height, and weight, were described by frequencies and propor- the 2 study groups (Table 1). After the primary vaccination, the
tions or means and standard deviations. The Pearson χ2 test GMTs of antibodies in the sIPV and IPV groups were 4149.7
or Student t test was used to examine differences between the and 493.5, respectively, against type 1 poliovirus (P < .01); 392.4
2 arms. All statistical analyses were performed using SAS 9.4 and 158.8, respectively, against type 2 (P < .01); and 1372.3 and
Software (SAS Institute, Cary, NC). 550.8, respectively, against type 3 (P < .01). Furthermore, in the
per-protocol population, the increases in GMTs of antibodies
RESULTS
against all 3 serotypes before and after the primary vaccination
Study Participants were significantly greater in the sIPV group as compared to
A total of 1249 infants were screened, and 1200 were recruited the IPV group (P < .01) overall and among seronegative sub-
into the study. Among all participants, 599 in the sIPV group jects. Additionally, after adjustment for the effect of maternal

Immunogenicity and Safety of a Sabin IPV • jid 2019:220 (15 November) • 1553
 Participants screened
n = 1249

49 were excluded:
• 6 had no informed consent
• 1 withdrew from the study
• 42 were not eligible

Participants enrolled and randomized

n = 1200

sIPV group IPV group

n = 600 n = 600

• 1 self-withdrew

Received the first dose Received the first dose

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n = 599 (safety set) n = 600 (safety set)
• 9 were out of town • 5 were out of town
• 4 self-withdrew • 2 self-withdrew
• 1 withdrew due to AE • 1 withdrew due to AE

Received the second dose Received the second dose

n = 585 n = 592
• 3 were out of town
• 3 self-withdrew • 3 were out of town
• 1 withdrew due to AE

Received the third dose Received the third dose

n = 578 n = 589

• 11 used protocol-
• 12 were unable/refused to prohibited vaccine
have blood specimen collected • 9 were unable/refused to have
• 9 were not vaccinated within blood specimen
required time collected after vaccination
• 4 used protocol- • 5 were not vaccinated within
prohibited vaccine required time
• 2 did not have blood specimen
collected within required time

Per-protocol set Per-protocol set

n = 553 n = 562

Figure 1. Participant flow through the study. AE, adverse event; IPV, control polio vaccine; sIPV, Sabin strain–based inactivated polio vaccine.

antibodies, the fold increase in GMTs of antibodies against the experiencing grade 3 solicited adverse events (P < .01). Redness
3 serotypes in both groups were all higher than the unadjusted was the most common local symptom, with reports by 4.7% of
fold increases (Table 2). guardians (28) in the sIPV arm and 2.8% (17) in the IPV arm
(P = .10). The most common systemic adverse event was fever,
Safety with reports in 61.6% of participants (369) in the sIPV arm and
During the primary vaccination series, the total number of par- 49.83% (299) in the IPV arm (P < .01; Table 3).
ticipants developing adverse events associated with vaccination Throughout the trial, 44 episodes of SAEs were reported
was 738 (61.6%), with 398 (66.4%) in the sIPV group and 340 for 27 participants (2.5%), of whom 14 (2.3%) were in the
(56.7%) in the IPV group (P < 0.01). Most adverse events were sIPV group and 13 (2.2%) were in the IPV group (P = .85).
solicited, with only 1.3% of guardians (8) in the sIPV group and The most common SAE was infectious pneumonia (in 16 par-
1.0% (6) in the IPV group reporting unsolicited adverse events ticipants [1.3%]), followed by upper respiratory tract infec-
(P = .60). Meanwhile, most solicited adverse events were classi- tion (in 4 [0.3%]) and lower respiratory tract infection (in 4
fied as minor (ie, severity grade 1 and 2), with only 0.5% of par- [0.3%]). No SAEs were associated with polio vaccines in the
ticipants (3) in the sIPV group and 1.5% (9) in the IPV group study.

1554 • jid 2019:220 (15 November) • Hu et al

Table 1. Baseline Characteristics of Study Participants Who Received Sabin Strain–Based Inactivated Polio Vaccine (sIPV) or Control IPV

Characteristics sIPV Group Control Group P

Safety population
Participants, no. 599 600
Male sex, no. (%) 343 (57.3) 319 (53.2) .15
Age, mo, mean ± SD 2.4 ± 0.3 2.4 ± 0.3 .63
Height, cm, mean ± SD 60.0 ± 2.6 60.1 ± 2.5 .86
Weight, kg, mean ± SD 6.3 ± 0.9 6.2 ± 0.8 .37
Per-protocol population
Participants, no. 553 562
Male sex, no. (%) 320 (57.9) 296 (52.7) .08
Age, mo, mean ± SD 2.4 ± 0.3 2.4 ± 0.3 .70
Height, cm, mean ± SD 60.0 ± 2.6 60.1 ± 2.5 .83
Weight, kg, mean ± SD 6.3 ± 0.9 6.2 ± 0.8 .24
Poliovirus type 1

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Seropositive, no. (%) 347 (62.8) 367 (65.3) .37
GMT (95% CI) 13.5 (12.2–14.9) 14.3 (12.9–15.8) .42
Poliovirus type 2
Seropositive, no. (%) 279 (50.5) 288 (51.3) .79
GMT (95% CI) 9.2 (8.5–10.0) 9.8 (8.9–10.7) .34
Poliovirus type 3
Seropositive, no. (%) 133 (24.1) 138 (24.6) .84
GMT (95% CI) 5.9 (5.5–6.4) 6.1 (5.6–6.5) .68

Abbreviations: CI, confidence interval; GMT, geometric mean titer.

DISCUSSION as effective as IPV in preventing poliovirus infection in infants

The study found that the immune responses against the 3 types aged 60–90 days, can be a reliable alternative to conventional
of poliovirus in the studied sIPV were not inferior to those IPV, and can be a good supplement to OPV in potentially pre-
achieved with the control IPV. It implies that the studied sIPV is venting or minimizing VDPV emergence and VAPP [11, 18, 22].

Table 2. Unadjusted and Maternal Antibody (Ab)–Adjusted Immunogenicity Profile, by Poliovirus Type, Among Study Participants After Primary Receipt of
Sabin Strain–Based Inactivated Polio Vaccine (sIPV) or Control IPV

Unadjusted Finding Maternal Ab–Adjusted Findinga

sIPV Group Control Group sIPV Group Control Group

Variable (n = 553) (n = 562) P (n = 553) (n = 562) P

Poliovirus type 1
Seropositive, no. (%) 553 (100.0) 562 (100.0) 1.00 553 (100.0) 562 (100.0) 1.00
Seroconversion, no. 542 529 550 558
Seroconversion rate, % (95% CI) 98.0 (96.5, 99.0) 94.1 (91.9, 95.9) <.01 99.5 (98.4, 99.9) 99.3 (98.2, 99.8) .72
GMT (95% CI) 4149.7 (3828.3, 4498.1) 493.5 (459.5, 530.0) <.01 4149.7 (3828.3, 4498.1) 493.5 (459.5, 530.0) <.01
Fold increase in GMT (95% CI) 307.9 (264.4, 358.5) 34.5 (30.6, 38.9) <.01 1302.5 (1158.0, 1465.0) 154.9 (140.0, 171.3) <.01
Poliovirus type 2
Seropositive, no. (%) 553 (100.0) 562 (100.0) 1.00 553 (100.0) 562 (100.0) 1.00
Seroconversion, no. 524 472 545 545
Seroconversion rate, % (95% CI) 94.8 (92.6, 96.5) 84.0 (80.7, 86.9) <.01 98.6 (97.2, 99.4) 97.0 (95.2, 98.2) .08
GMT (95% CI) 392.4 (362.5, 424.8) 158.8 (146.9, 171.5) <.01 392.4 (362.5, 424.8) 158.8 (146.9, 171.5) <.01
Fold increase in GMT (95% CI) 42.7 (37.5, 48.5) 16.2 (14.2, 18.5) <.01 136.0 (123.3, 150.0) 52.6 (47.2, 58.6) <.01
Poliovirus type 3
Seropositive, no. (%) 553 (100.0) 562 (100.0) 1.00 553 (100.0) 562 (100.0) 1.00
Seroconversion, no. 547 549 551 560
Seroconversion rate, % (95% CI) 98.9 (97.7, 99.6) 97.7 (96.1, 98.8) .11 99.6 (98.7, 100.0) 99.6 (98.7, 100.0) .99
GMT (95% CI) 1372.3 (1281.4, 1469.7) 550.8 (509.3, 595.7) <.01 1372.3 (1281.4, 1469.7) 550.8 (509.3, 595.7) <.01
Fold increase in GMT (95% CI) 231.5 (208.1, 257.6) 90.9 (81.4, 101.6) <.01 402.5 (369.4, 438.6) 159.7 (145.7, 175.1) <.01

Abbreviations: CI, confidence interval; GMT, geometric mean titer.

a
Analyses were performed using the adjusted baseline GMTs of seropositive subjects, calculated as the baseline GMT divided by 2n, where n is the number of days between collection of
the 2 blood specimens.

Immunogenicity and Safety of a Sabin IPV • jid 2019:220 (15 November) • 1555
Table 3. Solicited Adverse Events Caused by Primary Receipt of Sabin Strain–Based Inactivated Polio Vaccine (sIPV) or Control IPV, Overall and by
Severity Grade

Overall, No. (%) Grade 1 and 2, No. (%) Grade 3, No. (%)

sIPV Group IPV Group sIPV Group IPV Group sIPV Group IPV Group
Eventa (n = 599) (n = 600) Pb (n = 599) (n = 600) (n = 599) (n = 600) Pb

Local 33 (5.5) 23 (3.8) .17 33 (5.5) 21 (3.5) 0 (0.0) 2 (0.3) .17

Redness 28 (4.7) 17 (2.8) .10 28 (4.7) 16 (2.7) 0 (0.0) 1 (0.2) .09
Induration 8 (1.3) 9 (1.5) 1.00 8 (1.3) 8 (1.3) 0 (0.0) 1 (0.2) .81
Rash 2 (0.3) 4 (0.7) .69 2 (0.3) 3 (0.5) 0 (0.0) 1 (0.2) .41
Swelling 8 (1.3) 4 (0.7) .26 8 (1.3) 4 (0.7) … … .24
Systemic 389 (64.9) 334 (55.7) <.01 386 (64.4) 327 (54.5) 3 (0.5) 7 (1.2) <.01
Irritability 4 (0.7) 1 (0.2) .22 4 (0.7) 0 (0.0) 0 (0.0) 1 (0.2) .18
Vomiting 18 (3.0) 33 (5.5) .04 18 (3.0) 32 (5.3) 0 (0.0) 1 (0.2) .03
Fever 369 (61.6) 299 (49.8) <.01 369 (61.6) 298 (49.7) 0 (0.0) 1 (0.2) <.01

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Diarrhea 57 (9.5) 58 (9.7) 1.00 54 (9.0) 53 (8.8) 3 (0.5) 5 (0.8) .95
Drowsiness 14 (2.3) 14 (2.3) 1.00 14 (2.3) 14 (2.3) … … 1.00
Nausea 22 (3.7) 15 (2.5) .24 22 (3.7) 15 (2.5) … … .24
a
Participants could have multiple events.
b
By the Fisher exact test.

In China, the National Health Commission introduced a se- baseline, we found that the seroconversion rate against type 2
quential IPV/OPV vaccination schedule in the national vac- poliovirus in the IPV group was 100%.
cination program in May 2016, which has resulted in a huge There were some limitations in the study. First, the study only
demand for IPV [23]. Because the containment requirements used the Sabin strains from which the sIPV was generated to
and financial cost of sIPV are lower than those of conven- measure the neutralizing antibodies induced by the 2 vaccines;
tional IPV, sIPV is believed to be an affordable and practical the Salk strains generating the control IPV were not used in
IPV for use in developing countries, such as China [18, 22]. the assay. Therefore, the finding of a greater increase in GMTs
The study added scientific evidence of developing sIPV to induced by the sIPV than that induced by the IPV might be
eliminate both WPVs and VDPVs among young children in biased, as the antibody titer is associated with the virus strains
resource-limited areas. used in the microneutralization assay [26]. Nevertheless, pre-
In the study, no SAEs reported by the participants were asso- vious studies of other sIPV products, as well as unpublished
ciated with the studied sIPV. Most of the solicited local and sys- data of our studied sIPV, showed satisfactory cross-neutraliza-
temic adverse events caused by the sIPV were mild to moderate tion capacity across different WPV strains [22, 27]. Second, the
in severity. Fever was the most common adverse event resulting immunogenicity of the studied sIPV might be underestimated,
from sIPV, and the occurrence was more frequent in the sIPV because some participants might have received maternal anti-
group than in the IPV group. This finding is consistent with pre- bodies against polioviruses before the vaccination, owing to the
vious studies in China and may be explained by the fact that the universal use of OPV in China since 1970s, and we did not take
D antigen content in the studied sIPV is higher than that in the into account the decline in maternal antibodies over time [7].
control IPV [22, 24]. Because the current amount of D antigen The results of the immunogenicity analyses that adjusted for the
in the sIPV yielded a greater increase in antibody GMT than the effect of maternal antibodies provided evidence for this poten-
control IPV, the D antigen content in the sIPV can be moder- tial underestimation.
ately reduced, to control fever in future studies. This analysis revealed that the studied sIPV demonstrated an
Notably, in this study, the seroconversion rate against type immunogenicity profile noninferior to that of the conventional
2 poliovirus in the conventional IPV group (84%) was lower IPV, as well as a good safety profile. The launch of the studied
than that reported in several previous studies [19, 22, 24, 25]. sIPV may contribute to the polio eradication endgame in devel-
One possible reason for this unusually low seroconversion rate oping countries and the sustainment of a polio-free world.
is that the seropositivity rate (51.3%) and GMT (9.8) of antibod-
ies against type 2 poliovirus before vaccination was relatively Notes
higher in our study than in other studies, which might lead to Acknowledgments. We thank the staff of Guanyun Center
a lower proportion of seropositive subjects who could achieve for Disease Control and Prevention and the Pizhou Center for
a 4-fold increase in GMT (ie, seroconversion) after vaccina- Disease Control and Prevention for their fieldwork, including
tion. When only considering subjects who were seronegative at participant enrollment, vaccination, and safety assessment.

1556 • jid 2019:220 (15 November) • Hu et al

 Financial support. This work was supported by Sinovac 14. Patel M, Zipursky S, Orenstein W, Garon J, Zaffran M. Polio
Biotech. endgame: the global introduction of inactivated polio vac-
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rent employees of Sinovac Biotech. All other authors report no 15. Okayasu H, Sutter RW, Jafari HS, Takane M, Aylward RB.
potential conflicts of interest. Affordable inactivated poliovirus vaccine: strategies and
progress. J Infect Dis 2014; 210(Suppl 1):S459–64.
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