Immunization in India with trivalent and monovalent oral poliovirus vaccines of enhanced potency*

BRIEF COMMUNICATIONS Immunization in India with trivalent and monovalent oral poliovirus vaccines of enhanced potency * T. JACOB JOHN,1 L. V. DEVARAJAN,2 & A. BALASUBRAMANYAN 3 Abstract In an attempt to improve the serological response of infants in warm climates to oral poliovirus vaccine (OPV), the authors administered to 79 children be- tween 6 and 41 weeks ofage trivalent and monovalent OPV containing a virus dose 10 times as high as that found in the standard vaccine. The seroconversion rates following one dose of this trivalent OPV were 42 % to type 1 poliovirus, 85 % to type 2, and 31 % to type 3. These rates are only slightly better than those previously reported after one dose ofstandard trivalent OPV and much lower than those achieved after 3 doses. The seroconversion rates following one dose of the monovalent OPV of enhanced potency were 89%, 93 %, and 76%, respectively. These rates are comparable to those achieved after S doses of the standard trivalent OPV. Thus the refractoriness of host response was only partly overcome by enhancing the virus inoculum 10-fold. In an attempt to improve the rate of serocon- version of infants to oral polio vaccine (OPV) we increased the virus inoculum in the vaccine. Here we report the rates of response to both trivalent and monovalent OPV with a virus content 10 times higher than that contained in the standard trivalent OPV. Materials and methods The general setting of the study was similar to that described for an earlier investigation (4). Seventy- nine infants between 6 and 41 weeks of age and in an excellent state of nutrition were included in the study after permission had been obtained from their * From the Enterovirus Laboratory and Department of Child Health, Christian Medical College and Hospital, Vellore, India, and the Pasteur Institute, Coonoor, Tamil Nadu, India. 1 Professor of Microbiology and Chief, Enterovirus Laboratory. 2 Reader, Department of Child Health. Present address: New Maternity Hospital, Post Box No. 4080, Kuwait. 3 Director, Pasteur Institute, Coonoor. parents. A sample of blood from each infant was collected into a Dreyer's tube by heel puncture, as described earlier (4). Virus neutralizing antibody titres against poliovirus types 1, 2, and 3 were determined in these pre-vaccination sera in dilutions ranging from 1/ to 1/64 as described previously (4). Any serum showing no neutralizing activity against a virus type at a /8 dilution was considered antibody- negative to that type of poliovirus. At the second clinic visit, 4 weeks after the first, infants were assigned to different groups according to the results of antibody determinations, and were given OPV. Breast-feeding was withheld from the infants from 3 h before to 3 h after the adminis- tration of OPV. All vaccinations were performed from October to December 1973, inclusive. Four weeks after OPV administration, the infants were bled as described before and antibody titres were again determined. A portion ofa single standard serum containing antibodies to all serotypes of polio- virus was included in every test. Before a test was accepted as accurate, the antibody levels of these control serum specimens had to be no more than twice or no less than half the levels determined originally. The monovalent type 1, 2, and 3 oral poliovirus vaccines (Sabin's strains) were prepared at the Pasteur Institute, Coonoor, and transported frozen to the laboratory at Vellore. In the laboratory the vac- cine was thawed, divided into aliquots, and frozen again. Prior to the start of the study, sample aliquots were thawed and titrated to determine the virus content, in primary bonnet monkey kidney cell culture with 6 tubes for each decimal dilution, as described previously (4). The doses of vaccine viruses administered to the study population were: type 1, 107, TCID50; type 2, 106 TCID50; and type 3, 106.5 TCID50. Trivalent OPV was made up immediately before administration by mixing one dose of each of the 3 monovalent vaccines in a teaspoon. Monovalent OPV was given to 53 infants and trivalent OPV to 26 infants. 3494 - 115 - BULL. WORLD HEALTH ORGAN., Vol. 54, 1976 BRIEF COMMUNICATIONS Results Pre-vaccination antibody status. The 26 infants given trivalent OPV were seronegative to all types of poliovirus when they were included in the study. Among the 53 infants who received monovalent OPV, 48 were below 20 weeks of age. Of these, 8 were seronegative to the three types of poliovirus; 14 were seropositive to one type and 26 to two types. In general, their antibody levels were low-mostly in the range of 1/8-1/32; the levels had declined or disappeared in the post-vaccination sera except when type-specific antibody production was induced by monovalent OPV. For these reasons, pre- vaccination antibody was presumed to be of maternal origin. Five infants were over 20 weeks of age, includ- ing 3 over 32 weeks, and had higher levels of anti- body, which were unchanged or higher in the post-vaccination serum even though homologous vaccine was not given to them. Thus these five appeared to possess actively acquired antibody- three to type 2, one to type 3, and one to types 2 and 3. Antibody response to trivalent OPV. Of the 26 in- fants that received trivalent OPV, 23 (88.5%) sero- converted to one or more serotypes: 9 to one sero- type, 10 to 2 types, and 4 to 3 types of poliovirus. Type-specific seroconversions to type 1 were observed in 11 infants, to type 2 in 22 infants, and to type 3 in 8 infants. Three infants remained seronegative to all types. The type-specific seroconversion rates in these 26 infants are presented in Table 1. Antibody response to monovalent OPV. Among the 18 infants seronegative to type 1 who were given type 1 monovalent vaccine, 16 were antibody-positive 4 weeks later to type 1. No infant seroconverted to type 2 or 3. Thus the rate of seroconversion as a result ofone dose oftype 1 vaccine was 89% (Table 1). Table 1. Antibody response of infants to one dose of trivalent or of monovalent oral poliovirus vaccine of enhanced potency No. Type-specificVaccine No. sero- seroconversion rate (%) administered vaccinated converted Type 1 Type 2 Type 3 trivalent 26 23a (88.5%) 42 85 31 monovalent type 1 18 16 89 - - type 2 14 13 - 93 - type 3 21 16 - - 76 a Seroconverted to one or more types of poliovirus. Of the 14 infants seronegative to type 2 who were given type 2 monovalent vaccine, 13 (93 %) were found to have seroconverted (Table 1). Not one of these 14 infants seroconverted to type 1 or 3. Among the 21 infants seronegative to type 3 who were given type 3 vaccine, 16 (76%) became antibody- positive following immunization (Table 1). No infant in this group was found to have seroconverted to type 1 or 2. Discussion The standard trivalent OPV contains 106 TCID50 of type 1, 105 TCID50 of type 2, and 105'5 TCID50 of type 3 viruses per dose. We have earlier reported the type-specific seroconversion rates of infants given one dose of the standard OPV (4): 74% responded to one or more types of virus (29% to type 1, 67% to type 2, and 31% to type 3). In the present study, only 15% more infants responded to at least one serotype as a result of enhancing the potency of each component 10-fold. Type-specific seroconversion rates improved by only 13 % in the case of type 1, 18% for type 2, and not at all for type 3. Next we gave monovalent OPV of enhanced potency. The results were better than those obtained with the trivalent vaccine. The seroconversion rates were generally in the range of those obtained after 5 doses of the standard trivalent OPV; slightly higher for type 1 and slightly lower for types 2 and 3 (3). This phenomenon of better seroconversion rates with monovalent OPV than with trivalent OPV of equivalent dosage had been found in several studies (2, 6, 8). Owing to this drawback, a second dose was recommended; many investigators recom- mended an additional (third) dose to achieve sero- conversion rates approximating 100% (5, 6, 7). How- ever, in India, even with 5 doses of the standard trivalent OPV, we do not obtain close to 100% response to types 1 and 3 poliovirus. Three methods have been shown to improve sero- conversion rates of infants given OPV in tropical countries. The oral administration of horse serum prepared against human immunoglobulins, simul- taneously with monovalent type 1 vaccine, was shown to improve markedly the rate of sero- response (1). However, its effect on the response to types 2 and 3 vaccines and to trivalent vaccine has not been established. Moreover, the problems of availability and acceptance of horse serum are important factors in determining if it can be effec- tively applied in routine immunization practice. The present study shows that monovalent OPV 116 BRIEF COMMUNICATIONS 117 of enhanced potency may be used to elicit reason- ably satisfactory seroconversion rates. However, although there is no reason to suspect that a good vaccine containing a 10 times higher virus dose would be less safe than the standard vaccine, this has not yet been established. The increased cost of production and the inconvenience of handling three different vaccines make this a poor alternative. A single dose of the trivalent OPV of 10-fold enhanced potency did not prove to be a satisfactory immunogen; the seroconversion rates to types 1 and 3 were not satisfactory. Therefore multiple doses would seem to be necessary for satisfactory rates of response. It was shown earlier that 5 doses of the currently available trivalent OPV, given at intervals of 4 weeks or more, may achieve reasonably satis- factory seroconversion rates (3). For the present, this would seem to be a cheaper and more feasible method of immunizing infants in developing countries, espe- cially in the tropics, against poliomyelitis. AKNOWLEDGEMENNTS We thank Dr Malati Jadhav for permission to use the facilities of the Infant Immunization Clinic, Vellore, and P. Vijayarathnam, R. Elangovan, and L Suresh for tech- nical and administrative assistance. REFERENCES 1. DOMOK, I. ET AL. Factors affecting the efficacy of live poliovirus vaccine in warm climates. Bulletin of the World Health Organization, 51: 333-347 (1974). 2. GREAT BRITAIN, PUBLIC HEALTH LABORATORY SERVICE. Trial of living attenuated poliovirus vaccine. British medical journal, 2: 1037-1044 (1961). 3. JOHN, T. J. Antibody response of infants in the tropics to five doses of oral poliovaccine. British medical journal, 1: 811 (1976). 4. JOHN, T. J. ET AL. Effect of breast-feeding on sero- response of infants to oral poliovirus vaccination. Pediatrics, 57: 47-53 (1976). 5. PERKINS, F. T. ET AL. Response of three-month-old infants to 3 doses of trivalent oral poliomyelitis vac- cine. British medicaljournal, 1: 1573-1574 (1963). 6. SMORODINCEV, A. A. New data on live vaccines against poliomyelitis, mumps, and measles. Progress in medi- cal virology, 3: 245-310 (1961). 7. WINTER, P. A. ET AL. Serological results of polio- myelitis vaccine. South African medical journal, 37: 510-513 (1963). 8. ZA6EK, K. ET AL. Oral (Sabin) poliomyelitis vacci- nation. British medical journal, 1: 1091-1098 (1962).