Immunogenicity of bivalent types 1 and 3 oral poliovirus vaccine: a randomised, double-blind, controlled trial.
BACKGROUND
Poliovirus types 1 and 3 co-circulate in poliomyelitis-endemic countries. We aimed to assess the immunogenicity of a novel bivalent types 1 and 3 oral poliovirus vaccine (bOPV).


METHODS
We did a randomised, double-blind, controlled trial to assess the superiority of monovalent type 2 OPV (mOPV2), mOPV3, or bOPV over trivalent OPV (tOPV), and the non-inferiority of bivalent vaccine compared with mOPV1 and mOPV3. The study was done at three centres in India between Aug 6, 2008, and Dec 26, 2008. Random allocation was done by permuted blocks of ten. The primary outcome was seroconversion after one monovalent or bivalent vaccine dose compared with a dose of trivalent vaccine at birth. The secondary endpoints were seroconversion after two vaccine doses compared with after two trivalent vaccine doses and cumulative two-dose seroconversion. Parents or guardians and study investigators were masked to treatment allocation. Because of multiple comparisons, we defined p≤0·01 as statistically significant. This trial is registered with Current Controlled Trials, ISRCTN 64725429.


RESULTS
900 newborn babies were randomly assigned to one of five vaccine groups (about 180 patients per group); of these 70 (8%) discontinued, leaving 830 (92%) for analysis. After the first dose, seroconversion to poliovirus type 1 was 20% for both mOPV1 (33 of 168) and bOPV (32 of 159) compared with 15% for tOPV (25 of 168; p>0·01), to poliovirus type 2 was 21% (35 of 170) for mOPV2 compared with 25% (42 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 12% (20 of 165) for mOPV3 and 7% (11 of 159) for bOPV compared with 4% (7 of 168) for tOPV (mOPV3 vs tOPV p=0·01; bOPV vs tOPV; p>0·01). Cumulative two-dose seroconversion to poliovirus type 1 was 90% (151 of 168) for mOPV1 and 86% (136 of 159) for bOPV compared with 63% (106 of 168) for tOPV (p<0·0001), to poliovirus type 2 was 90% (153 of 170) for mOPV2 compared with 91% (153 of 168) for tOPV (p>0·01), and to poliovirus type 3 was 84% (138 of 165) for mOPV3 and 74% (117 of 159) for bOPV compared with 52% (87 of 168) for tOPV (p<0·0001). The vaccines were well tolerated. 19 serious adverse events occurred, including one death; however, these events were not attributed to the trial interventions.


CONCLUSIONS
The findings show the superiority of bOPV compared with tOPV, and the non-inferiority of bOPV compared with mOPV1 and mOPV3.


BACKGROUND
GAVI Alliance, World Health Organization, and Panacea Biotec.
Sutter
Roland W
RW
World Health Organization, Geneva, Switzerland. sutterr@who.int
John
T Jacob
TJ
Jain
Hemant
H
Agarkhedkar
Sharad
S
Ramanan
Padmasani Venkat
PV
Verma
Harish
H
Deshpande
Jagadish
J
Singh
Ajit Pal
AP
Sreevatsava
Meghana
M
Malankar
Pradeep
P
Burton
Anthony
A
Chatterjee
Arani
A
Jafari
Hamid
H
Aylward
R Bruce
RB
D000914:Antibodies, Viral / Q000097:blood; D004311:Double-Blind Method; D005243:Feces / Q000821:virology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011051:Poliomyelitis / Q000517:prevention & control; D017955:Poliovirus / Q000276:immunology* / Q000302:isolation & purification; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects / Q000276:immunology*; D014611:Vaccination
D000914:Antibodies, Viral; D011055:Poliovirus Vaccine, Oral