Inactivated hepatitis A vaccine: a safety and immunogenicity study in health professionals Morton Davidson, Saul Krugman§ and Laurie A. Sandman The safety and immunogenicity o f an inactivated hepatitis A vaccine ( H M 1 7 5 strain) were evaluated in 150 seronegative health professionals. The age range was 2 1 4 5 years and the mean age was 30 years. The vaccine was administered at a dose o f 720 E L I S A units ( E U ) to 73 vaccinees at O, 1 and 6 months, and to 77 vaccinees at O, 1 and 12 months. The seroconversion rates were 88 and 9 0 % in the two groups, respectively, one month after the first inoculation and 99 and 100% one month after the second inoculation. The geometric mean antibody titres were similar in both groups, exceeding 3000 m l U / m l one month after the third inoculation. The vaccine was well tolerated. The most frequent side effect was transient soreness at the site of the inoculation. No serious adverse reactions were observed. The study demonstrated that the H M 1 7 5 inactivated hepatitis A vaccine was safe and highly immunogenic. Keywords: Hepatitis A; HM175 strain; health professionals
INTRODUCTION The successful cultivation of hepatitis A virus (HAV) in cell culture by Provost and Hilleman in 1979 provided the technology needed for the development of inactivated as well as live attenuated HAV vaccines ~. By the late 1980s, the propagation of large quantities of HAV in the human diploid cell line, MRC-5, was followed by the development of various candidate inactivated vaccines z3. Preliminary studies with the vaccine prepared by SmithKline Beecham Biologicals using the HMI75 HAV strain revealed that it was safe and immunogenic 2. The objective of the present study was to evaluate the safety and immunogenicity of the vaccine using two schedules in 150 seronegative health professionals. The protocol was approved by the New York University Medical Center Institutional Review Board, all participants were informed of the nature of the study and their written consent was obtained. MATERIALS AND METHODS The volunteers included in the study were assigned randomly to two groups. Group A consisted of 77 adults whose mean age was 30 years (range 21-65 years). They were vaccinated at 0, 1 and 6 months and blood samples were obtained at 0, 1, 2, 6, 7 and 13 months. Group B consisted of 73 adults whose mean age was 29 years New York University Medical Center, 550 First Avenue, New York, NY 10016, USA. §To whom correspondence should be addressed 0264-410X/92/100S119-02 © 1992Butterworth-HeinemannLtd
(range 22-63 years). They were vaccinated at 0, 1, and 12 months and blood samples were obtained at 0, 1, 2, 7, 12 and 13 months. All vaccinees received the HM 175 inactivated HAV. The antigen content of the 1 ml dose was 720 ELISA Units (EU). They were asked to record on a diary card any adverse reaction occuring within 3 days postvaccination. The serum specimens were titrated for hepatitis A antibody (anti-HAV) using an ELISA inhibition assay and titres were expressed as mIU/ml. Seroconversion rates ( > 20 mIU/ml) and geometric mean antibody titres in seroconvertors were determined. RESULTS
Safety The most common side effect was transient pain and tenderness at the site of inoculation. It was reported in 27% of vaccinees after the first inoculation, in 18% after the second and in 14% after the third. No serious systemic reactions were reported. In general, the vaccine was well tolerated and the vaccinees continued their routine activities without interruption.
Immunogenicity The percentage antibody response and geometric mean antibody titres of 77 vaccinees in group A are summarized in Table 1 and Figure 1. The data for the 73 vaccinees in group B are shown in Table 2 and Figure 2. The seroconversion rates of the combined groups were as follows: 89% (134/150) one month after the first dose;
Vaccine, Vol. 10, Suppl. 1, 1992
$119
I n a c t i v a t e d hepatitis A vaccine in health professionals." M. D a v i d s o n et al. Table 1 Seroconversion rates ( > 20 mlU/ml) and geometric mean antibody titres (GMT) following three doses of hepatitis A vaccine (720 El.U) at 0, 1 and 6 months
No. of responders/total (%) GMT (mlU/ml)
Day 0
Month 1
Month 2
Month 6
Month 7
Month 13
0/77 (-) -
68/77 (88) 303
74/75 (99) 603
67/71 (94) 315
72/72 (100) 3000
40/40 (100) 1406
Age of vaccinees: range 21-65 years, mean 30 years
Table 2 Seroconversion rates ( > 20 mlU/ml) and geometric mean antibody titres (GMT) following three doses of hepatitis A vaccine (720 El.U) at 0, 1 and 12 months
No. of responders/total (%) GMT (mlU/ml)
Day 0
Month 1
Month 2
Month 7
Month 12
Month 13
0/73 (-) -
66/73 (90) 273
71/71 (100) 536
67/68 (99) 285
43/45 (96) 228
38/38 (100) 3790
Age o1 vaccinees: range 22-63 years, mean 29 years
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INTRODUCTION The successful cultivation of hepatitis A virus (HAV) in cell culture by Provost and Hilleman in 1979 provided the technology needed for the development of inactivated as well as live attenuated HAV vaccines ~. By the late 1980s, the propagation of large quantities of HAV in the human diploid cell line, MRC-5, was followed by the development of various candidate inactivated vaccines z3. Preliminary studies with the vaccine prepared by SmithKline Beecham Biologicals using the HMI75 HAV strain revealed that it was safe and immunogenic 2. The objective of the present study was to evaluate the safety and immunogenicity of the vaccine using two schedules in 150 seronegative health professionals. The protocol was approved by the New York University Medical Center Institutional Review Board, all participants were informed of the nature of the study and their written consent was obtained. MATERIALS AND METHODS The volunteers included in the study were assigned randomly to two groups. Group A consisted of 77 adults whose mean age was 30 years (range 21-65 years). They were vaccinated at 0, 1 and 6 months and blood samples were obtained at 0, 1, 2, 6, 7 and 13 months. Group B consisted of 73 adults whose mean age was 29 years New York University Medical Center, 550 First Avenue, New York, NY 10016, USA. §To whom correspondence should be addressed 0264-410X/92/100S119-02 © 1992Butterworth-HeinemannLtd
(range 22-63 years). They were vaccinated at 0, 1, and 12 months and blood samples were obtained at 0, 1, 2, 7, 12 and 13 months. All vaccinees received the HM 175 inactivated HAV. The antigen content of the 1 ml dose was 720 ELISA Units (EU). They were asked to record on a diary card any adverse reaction occuring within 3 days postvaccination. The serum specimens were titrated for hepatitis A antibody (anti-HAV) using an ELISA inhibition assay and titres were expressed as mIU/ml. Seroconversion rates ( > 20 mIU/ml) and geometric mean antibody titres in seroconvertors were determined. RESULTS
Safety The most common side effect was transient pain and tenderness at the site of inoculation. It was reported in 27% of vaccinees after the first inoculation, in 18% after the second and in 14% after the third. No serious systemic reactions were reported. In general, the vaccine was well tolerated and the vaccinees continued their routine activities without interruption.
Immunogenicity The percentage antibody response and geometric mean antibody titres of 77 vaccinees in group A are summarized in Table 1 and Figure 1. The data for the 73 vaccinees in group B are shown in Table 2 and Figure 2. The seroconversion rates of the combined groups were as follows: 89% (134/150) one month after the first dose;
Vaccine, Vol. 10, Suppl. 1, 1992
$119
I n a c t i v a t e d hepatitis A vaccine in health professionals." M. D a v i d s o n et al. Table 1 Seroconversion rates ( > 20 mlU/ml) and geometric mean antibody titres (GMT) following three doses of hepatitis A vaccine (720 El.U) at 0, 1 and 6 months
No. of responders/total (%) GMT (mlU/ml)
Day 0
Month 1
Month 2
Month 6
Month 7
Month 13
0/77 (-) -
68/77 (88) 303
74/75 (99) 603
67/71 (94) 315
72/72 (100) 3000
40/40 (100) 1406
Age of vaccinees: range 21-65 years, mean 30 years
Table 2 Seroconversion rates ( > 20 mlU/ml) and geometric mean antibody titres (GMT) following three doses of hepatitis A vaccine (720 El.U) at 0, 1 and 12 months
No. of responders/total (%) GMT (mlU/ml)
Day 0
Month 1
Month 2
Month 7
Month 12
Month 13
0/73 (-) -
66/73 (90) 273
71/71 (100) 536
67/68 (99) 285
43/45 (96) 228
38/38 (100) 3790
Age o1 vaccinees: range 22-63 years, mean 29 years
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