Immunogenicity of Tetravalent Rhesus Rotavirus Vaccine Administered With Buffer and Oral Polio Vaccine Donna J.
Ing, MPH; Roger I. Glass, MD; Patricia A. Woods; Murri Simonetti; Mark A. Pallansch, PhD; Wallace D. Wilcox, MD; Bruce L. Davidson, MD; Alan J. Sievert, MD
\s=b\ Between
January and November 1989, we studied 174 infants aged 6 to 16 weeks in a randomized clinical trial to (1) determine the immunogenicity of a single dose of tetravalent rhesus rotavirus vaccine (RRV-TV) when administered with three different buffer regimens: no antacid buffer and small-volume (2.5-mL) and large-volume (30-mL) antacid buffer; and (2) examine the potential interference of RRV-TV on the immune response to oral polio vaccine. Immunogenicity of RRV-TV, measured as a fourfold rise in antibody titers to rotavirus, was similar in the groups receiving small- and large-dose buffer (45% and 49%, respectively) and significantly less in the group that received RRV-TV alone (23%). Administration of RRV-TV with oral polio vaccine did not significantly interfere with the neutralization response of oral polio vaccine poliovirus serotypes 1, 2, or 3, and overall, 29%, 87%, and 24% of the infants had a fourfold rise in titer to each serotype, respectively. (AJDC. 1991;145:892-897)
of the (RV) impor¬ Worldwide,infantsofand children.1,2 dehydrating diarrhea and researchers rotavirus
tant
causes
is
one
most
severe
vomiting in Many have emphasized the need for a vaccine that can be in¬ corporated into routine childhood immunization pro¬ grams .2'3 Several vaccines have been developed and tested that have shown promising results in small field trials.4"7 One, the oral tetravalent rhesus rotavirus vaccine (RRVTV), has advanced to a large-scale trial at 22 centers in the
United States involving nearly 1000 infants who are re¬ ceiving three oral doses. If this trial demonstrates signif-
Accepted
publication January 3, 1991. Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga (Ms Ing, Drs Glass and Wilcox, and Ms Simonetti); Viral Gastroenteritis Unit, Respiratory and Enteric Virus for
From the
Branch, Division of Viral and Rickettsial Diseases, Center for Infectious Diseases, Centers for Disease Control, US Department of Health and Human Services, Public Health Service, Atlanta (Drs Glass and Pallansch and Ms Woods); Wyeth-Ayerst Research, Clinical Research and Development, Philadelphia, Pa (Dr Davidson); and Division of Physical Health, DeKalb County Board of Health, Decatur, Ga (Dr Sievert). Use of trade names is for identification only and does not constitute endorsement by the Public Health Service or the US Department of Health and Human Services. Reprint requests to Division of Viral and Rickettsial Diseases, Centers for Disease Control, 1600 Clifton Rd, Atlanta, GA 30333 (Dr Glass).
efficacy, this vaccine might be considered for incor¬ poration into routine childhood immunization programs icant
in the United States. In vaccine studies conducted to date, RV vaccines have been administered with large volumes of buffer and sep¬ arated by periods of 2 weeks from oral poliovirus vaccine
(OPV) immunization. Each of these conditions would
make the incorporation of RV vaccine into the routine schedule of childhood immunizations logistically difficult: administration separate from that of the OPV would re¬ quire extra visits, and the large-dose buffer is more difficult to administer than the vaccine itself. In previous studies, buffer was shown to be important to ensure a good immunogenic response, but the dose of buffer has never been titered against the immunogenicity of the RRV-TV vaccine to determine if a smaller dose would have a com¬ parable effect.8 Furthermore, since rotavirus vaccine should optimally be administered before 2 to 3 months of age, it could ideally be given together with OPV if there were no interference in the immunogenicity of either vac¬ cine. This issue has been addressed in previous studies9"12 but has not been adequately resolved. This study was conducted (1) to determine the immu¬ nogenicity of RRV-TV vaccine when administered with one of three different buffer regimens (large-volume [30-mL], small-volume [2.5-mL], and no buffer) and (2) to examine the interference of RRV-TV in the immune re¬ sponse to OPV.
SUBJECTS AND METHODS
Subjects
The study was conducted at five well-baby and immunization clinics of the DeKalb County Board of Health, Decatur, Ga, during the period between January and November 1989. Healthy infants 6 to 16 weeks of age who came to the clinic for their first well-baby visit and immunization (diphtheria-pertussis-tetanus and OPV) were recruited into the study. A pediatrician or study nurse re¬ viewed each infant's medical history and examined the child. In¬ fants were excluded if they (1) had had diarrhea, vomiting, or fever within the past week, (2) had been exposed to chickenpox within the past 3 weeks, (3) had had any serious illness since birth, (4) lived in a home with no telephone, or (5) had anyone in the household who was pregnant or immunocompromised. The study was ex¬ plained to parents, and written informed consent was obtained. The study was approved by the Human Investigations Committee of Emory University, School of Medicine, Atlanta, Ga, by the Human
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Pennsylvania User on 06/14/2015
Table 1.—Characteristics of Participants in Four Study Groups* No.
RRV-TV/OPV,
RRV-TV/OPV,
Small Buffer (N 44)
Large Buffer
(16) 26 (59) 11 (25)
15 (34) 16 (36)
10 (21) 25 (53)
13 (30)
(52) (48)
RRV-TV/OPV, No Buffer
Characteristic
Age, wk 7-8
9-10 >11
Sex M
(N = 44) 7
23
F
21
Race W
4
B
37
(9) (84) 3 (7)
Other Birth weight, g
Ing, MPH; Roger I. Glass, MD; Patricia A. Woods; Murri Simonetti; Mark A. Pallansch, PhD; Wallace D. Wilcox, MD; Bruce L. Davidson, MD; Alan J. Sievert, MD
\s=b\ Between
January and November 1989, we studied 174 infants aged 6 to 16 weeks in a randomized clinical trial to (1) determine the immunogenicity of a single dose of tetravalent rhesus rotavirus vaccine (RRV-TV) when administered with three different buffer regimens: no antacid buffer and small-volume (2.5-mL) and large-volume (30-mL) antacid buffer; and (2) examine the potential interference of RRV-TV on the immune response to oral polio vaccine. Immunogenicity of RRV-TV, measured as a fourfold rise in antibody titers to rotavirus, was similar in the groups receiving small- and large-dose buffer (45% and 49%, respectively) and significantly less in the group that received RRV-TV alone (23%). Administration of RRV-TV with oral polio vaccine did not significantly interfere with the neutralization response of oral polio vaccine poliovirus serotypes 1, 2, or 3, and overall, 29%, 87%, and 24% of the infants had a fourfold rise in titer to each serotype, respectively. (AJDC. 1991;145:892-897)
of the (RV) impor¬ Worldwide,infantsofand children.1,2 dehydrating diarrhea and researchers rotavirus
tant
causes
is
one
most
severe
vomiting in Many have emphasized the need for a vaccine that can be in¬ corporated into routine childhood immunization pro¬ grams .2'3 Several vaccines have been developed and tested that have shown promising results in small field trials.4"7 One, the oral tetravalent rhesus rotavirus vaccine (RRVTV), has advanced to a large-scale trial at 22 centers in the
United States involving nearly 1000 infants who are re¬ ceiving three oral doses. If this trial demonstrates signif-
Accepted
publication January 3, 1991. Department of Pediatrics, Emory University School of Medicine, Atlanta, Ga (Ms Ing, Drs Glass and Wilcox, and Ms Simonetti); Viral Gastroenteritis Unit, Respiratory and Enteric Virus for
From the
Branch, Division of Viral and Rickettsial Diseases, Center for Infectious Diseases, Centers for Disease Control, US Department of Health and Human Services, Public Health Service, Atlanta (Drs Glass and Pallansch and Ms Woods); Wyeth-Ayerst Research, Clinical Research and Development, Philadelphia, Pa (Dr Davidson); and Division of Physical Health, DeKalb County Board of Health, Decatur, Ga (Dr Sievert). Use of trade names is for identification only and does not constitute endorsement by the Public Health Service or the US Department of Health and Human Services. Reprint requests to Division of Viral and Rickettsial Diseases, Centers for Disease Control, 1600 Clifton Rd, Atlanta, GA 30333 (Dr Glass).
efficacy, this vaccine might be considered for incor¬ poration into routine childhood immunization programs icant
in the United States. In vaccine studies conducted to date, RV vaccines have been administered with large volumes of buffer and sep¬ arated by periods of 2 weeks from oral poliovirus vaccine
(OPV) immunization. Each of these conditions would
make the incorporation of RV vaccine into the routine schedule of childhood immunizations logistically difficult: administration separate from that of the OPV would re¬ quire extra visits, and the large-dose buffer is more difficult to administer than the vaccine itself. In previous studies, buffer was shown to be important to ensure a good immunogenic response, but the dose of buffer has never been titered against the immunogenicity of the RRV-TV vaccine to determine if a smaller dose would have a com¬ parable effect.8 Furthermore, since rotavirus vaccine should optimally be administered before 2 to 3 months of age, it could ideally be given together with OPV if there were no interference in the immunogenicity of either vac¬ cine. This issue has been addressed in previous studies9"12 but has not been adequately resolved. This study was conducted (1) to determine the immu¬ nogenicity of RRV-TV vaccine when administered with one of three different buffer regimens (large-volume [30-mL], small-volume [2.5-mL], and no buffer) and (2) to examine the interference of RRV-TV in the immune re¬ sponse to OPV.
SUBJECTS AND METHODS
Subjects
The study was conducted at five well-baby and immunization clinics of the DeKalb County Board of Health, Decatur, Ga, during the period between January and November 1989. Healthy infants 6 to 16 weeks of age who came to the clinic for their first well-baby visit and immunization (diphtheria-pertussis-tetanus and OPV) were recruited into the study. A pediatrician or study nurse re¬ viewed each infant's medical history and examined the child. In¬ fants were excluded if they (1) had had diarrhea, vomiting, or fever within the past week, (2) had been exposed to chickenpox within the past 3 weeks, (3) had had any serious illness since birth, (4) lived in a home with no telephone, or (5) had anyone in the household who was pregnant or immunocompromised. The study was ex¬ plained to parents, and written informed consent was obtained. The study was approved by the Human Investigations Committee of Emory University, School of Medicine, Atlanta, Ga, by the Human
Downloaded From: http://archpedi.jamanetwork.com/ by a University of Pennsylvania User on 06/14/2015
Table 1.—Characteristics of Participants in Four Study Groups* No.
RRV-TV/OPV,
RRV-TV/OPV,
Small Buffer (N 44)
Large Buffer
(16) 26 (59) 11 (25)
15 (34) 16 (36)
10 (21) 25 (53)
13 (30)
(52) (48)
RRV-TV/OPV, No Buffer
Characteristic
Age, wk 7-8
9-10 >11
Sex M
(N = 44) 7
23
F
21
Race W
4
B
37
(9) (84) 3 (7)
Other Birth weight, g
