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Antibody Response to Inactivated Influenza Vaccines of Various Antigenic Concentrations Kevin M. Sullivan,* Arnold S. Monto, and David A. Foster
From the Department of Epidemiology, University of Michigan, Ann Arbor
R>Ur inactivated influenza vaccines (containing the recommended antigens for the 1985-1986 influenza season) of various antigenic concentration levels were randomly administered to 140 study participants. The effect of the increasing antigen concentration resulted in significantly higher influenza hemagglutination inhibition (HI) antibody levels 3 weeks after vaccination for the A/HINI antigen but not for the A/H3N2 or B antigens. Also, at 3 weeks after vaccination, there were significantly lower antibody titer levels associated with increasing age for the AIHINI and B antigens (adjusting for the prevaccination antibody titer and antigen content).
Materials and Methods Study design, subjects, and collection of symptominformation af ter vaccination. Students at the University of Michigan and associated personnel ~18 years old were eligible to participate in this trial. A total of 140 individuals were randomly assigned to one of four vaccine groups (35/group). Each group received a vaccine produced by the same manufacturer (Evans Biologicals, UK) but of different antigen content. A fifth vaccine produced by another manufacturer (ParkeDavis, Morris Plains, NJ) was randomly assigned to 55 individuals
Received 6 February 1989; revised 25 August 1989. Informed consent was obtained from participants, and guidelines for human experimentation established by the School of Public Health, University of Michigan, were followed. Grant support: Evans Biologicals, Ltd. Reprints and correspondence: Mr. Kevin M. Sullivan, Centers for Disease Control, 1600 Clifton Road, N.E., MS A08, Atlanta, GA 30333. * Present address: Centers for Disease Control, Atlanta, GA. The Journal of Infectious Diseases 1990;161:333-335 © 1990 by The University of Chicago. All rights reserved. 0022-1899/90/6102-0028$01.00
but is not the subject of this report since it was comparable to the Evans vaccine of the same antigenic content. Exclusions for eligibility were history of allergy to eggs, past or current neurologic conditions, and respiratory illness or fever at the time of vaccination. Serum samples were collected by venipuncture before vaccination, and follow-upblood specimens were collected at 3 weeks and 6 months after vaccination. Symptoms were self-reported on preprinted forms for the evening of vaccination and the first and second days thereafter. Symptom information was collected on malaise, myalgia, headache, nausea, vomiting, diarrhea, dizziness, chills, cough, sore throat, and pain or tenderness at the site of vaccination. Temperatures were recorded before and 6, 12, 24, and 48 h after vaccination. Three weeks after vaccination a follow-up questionnaire, similar to that used in previous influenza vaccine trials [2], was given to study participants to collect information about respiratory and neurologic symptoms that may have occurred after the last collection of symptom data. Vaccines. Vaccines (Evans Biologicals) contained the following antigens: A/Philippines/2/82 (H3N2), A/Chile/lI83 (H1N1),and B/ USSR/100/83, the antigens recommended by the Advisory Committee on Immunization Practices for use in the 1985-1986 influenza season [3]. Vaccine A contained 7.5 Itg of each antigen; vaccine B, 15 Itg; vaccine C, 30 Itg; and vaccine D, 45 Itg of the influenza B antigen and 15 Itg of each of the influenza A antigens. The vaccines were prepared by disruption of the virus by triton in a sucrose gradient [4]. This method of disrupting influenza virus and purifying the antigens for vaccines has been licensed and used in the UK for many years. Vaccinesproduced by this method have been shown to be antigenic and essentially free of core protein [5, 6]. Serologictesting. Serum hemagglutination-inhibition (HI) tests were performed using standard techniques described elsewhere [7]. The initial serum dilution used was 1:8 and twofold serial dilutions were carried out to 1:256. The following antigens prepared at the Centers for Disease Control (Atlanta) were used: A/Philippines/2/82 (H3N2), A/Chile/lI83 (H1N1), and B/USSR/l00/83 ether-split virus. Pre- and 3-week postvaccination serum samples were tested in parallel, as were the 3-week and 6-month postvaccination sera. Analyses. The X2 test and analysis of variance (ANOVA) were used. Titers of
Antibody Response to Inactivated Influenza Vaccines of Various Antigenic Concentrations Kevin M. Sullivan,* Arnold S. Monto, and David A. Foster
From the Department of Epidemiology, University of Michigan, Ann Arbor
R>Ur inactivated influenza vaccines (containing the recommended antigens for the 1985-1986 influenza season) of various antigenic concentration levels were randomly administered to 140 study participants. The effect of the increasing antigen concentration resulted in significantly higher influenza hemagglutination inhibition (HI) antibody levels 3 weeks after vaccination for the A/HINI antigen but not for the A/H3N2 or B antigens. Also, at 3 weeks after vaccination, there were significantly lower antibody titer levels associated with increasing age for the AIHINI and B antigens (adjusting for the prevaccination antibody titer and antigen content).
Materials and Methods Study design, subjects, and collection of symptominformation af ter vaccination. Students at the University of Michigan and associated personnel ~18 years old were eligible to participate in this trial. A total of 140 individuals were randomly assigned to one of four vaccine groups (35/group). Each group received a vaccine produced by the same manufacturer (Evans Biologicals, UK) but of different antigen content. A fifth vaccine produced by another manufacturer (ParkeDavis, Morris Plains, NJ) was randomly assigned to 55 individuals
Received 6 February 1989; revised 25 August 1989. Informed consent was obtained from participants, and guidelines for human experimentation established by the School of Public Health, University of Michigan, were followed. Grant support: Evans Biologicals, Ltd. Reprints and correspondence: Mr. Kevin M. Sullivan, Centers for Disease Control, 1600 Clifton Road, N.E., MS A08, Atlanta, GA 30333. * Present address: Centers for Disease Control, Atlanta, GA. The Journal of Infectious Diseases 1990;161:333-335 © 1990 by The University of Chicago. All rights reserved. 0022-1899/90/6102-0028$01.00
but is not the subject of this report since it was comparable to the Evans vaccine of the same antigenic content. Exclusions for eligibility were history of allergy to eggs, past or current neurologic conditions, and respiratory illness or fever at the time of vaccination. Serum samples were collected by venipuncture before vaccination, and follow-upblood specimens were collected at 3 weeks and 6 months after vaccination. Symptoms were self-reported on preprinted forms for the evening of vaccination and the first and second days thereafter. Symptom information was collected on malaise, myalgia, headache, nausea, vomiting, diarrhea, dizziness, chills, cough, sore throat, and pain or tenderness at the site of vaccination. Temperatures were recorded before and 6, 12, 24, and 48 h after vaccination. Three weeks after vaccination a follow-up questionnaire, similar to that used in previous influenza vaccine trials [2], was given to study participants to collect information about respiratory and neurologic symptoms that may have occurred after the last collection of symptom data. Vaccines. Vaccines (Evans Biologicals) contained the following antigens: A/Philippines/2/82 (H3N2), A/Chile/lI83 (H1N1),and B/ USSR/100/83, the antigens recommended by the Advisory Committee on Immunization Practices for use in the 1985-1986 influenza season [3]. Vaccine A contained 7.5 Itg of each antigen; vaccine B, 15 Itg; vaccine C, 30 Itg; and vaccine D, 45 Itg of the influenza B antigen and 15 Itg of each of the influenza A antigens. The vaccines were prepared by disruption of the virus by triton in a sucrose gradient [4]. This method of disrupting influenza virus and purifying the antigens for vaccines has been licensed and used in the UK for many years. Vaccinesproduced by this method have been shown to be antigenic and essentially free of core protein [5, 6]. Serologictesting. Serum hemagglutination-inhibition (HI) tests were performed using standard techniques described elsewhere [7]. The initial serum dilution used was 1:8 and twofold serial dilutions were carried out to 1:256. The following antigens prepared at the Centers for Disease Control (Atlanta) were used: A/Philippines/2/82 (H3N2), A/Chile/lI83 (H1N1), and B/USSR/l00/83 ether-split virus. Pre- and 3-week postvaccination serum samples were tested in parallel, as were the 3-week and 6-month postvaccination sera. Analyses. The X2 test and analysis of variance (ANOVA) were used. Titers of
