Influenza vaccination in kidney transplant recipients: cellular and humoral immune responses.

Influenza infection in renal transplant recipients may cause either morbidity and mortality or acute allograft rejection; thus, routine annual influenza vaccination should be considered. We have studied the humoral and cellular immune responses to influenza virus antigens before and after trivalent vaccine administration in 13 patients and 16 control subjects. The patients, nine of whom were either on alternate-day or low-dose daily steroid therapy, showed highly significant serum hemagglutination-inhibition antibody responses to each influenza virus strain, There was no significant change in mean lymphocyte stimulation index to any influenza virus strain after vaccination in either group. There was no correlation in the patient group between hemagglutination-inhibition antibody titer or response, or lymphocyte stimulation index or response, and the degree of allograft function or dose or duration of immunosuppressive therapy. The vigorous antibody response and the evidence of cellular immunity support the efficacy of influenza vaccination in these patients.

Ether-treated, subunit Hsw1N1 influenza vaccines: response of immunologically primed subjects to two antigenic variants.

Two bivalent, ether-treated, subunit influenza vaccines were compared in adults greater than or equal to 45 years old. Both vaccines contained 200 chick cell-agglutinating (CCA) units of A/Victoria/3/75 antigen/dose. The Hsw1N1 components, also at a level of 200 CCA units/dose and designated A/Shope and A/X-53, were antigenically representative of the A/swine/1976/31 and A/New Jersey/8/76 viruses, respectively. A/Shope virus possessed about 100 times more neuraminidase activity than A/X-53 virus. The two vaccine groups had equivalent geometric mean titers (GMTs) of antibody to A/NJ virus, with about 95% of each group having titers of greater than or equal to 1:40 after vaccination. Group GMTs of antibody to A/Vic virus were also equivalent. Failure of the A/X-53 vaccinees to respond according to the dogma of original antigenic sin and a highly significant between-group difference in response to A/PR/8/34 antigen are interpreted as due to a difference in vaccine neuraminidase levels. It is suggested that, although A/Shope was as serologically effective against A/NJ virus as A/X-53 in this age group, under similar conditions a recombinant with the A/NJ hemagglutinin and the stable A/swine neuraminidase antigens might be more effective against A/NJ than either of the present vaccines.

Reactions and serologic responses after administration of inactivated monovalent influenza A/swine virus vaccines. I. Immunization of children and adults with influenza A/Shope virus vaccines.

Reactivity and immunogenicity of three inactivated, zonally purified, monovalent influenza A/swine virus vaccines were studied in children and adults. Each dose of vaccine contained either 400 chick cell-agglutinating (CCA) units/0.5 ml or 200 CCA units/0.25 ml. The vaccines contained either whole virus or ether-extracted, subunit virus with or without 1.5 mg of A1PO4/0.5 ml. Children younger than 10 years of age received a half dose. Substantial system reactions, including temperature increases of 2.2 F-4.9 F, were observed in all children who received whole-virus vaccines. In contrast, ether-extracted, subunit vaccines (with or without A1PO4) were minimally pyrogenic in 185 subjects. Two doses of subunit vaccine in subjects younger than 25 years of age were immunologically equivalent to a single dose in older subjects. We concluded that two doses of ether-extracted, subunit virus vaccine with Hsw1N1 antigen, administered at least four weeks apart, are serologically effective for immunization of seronegative subjects of any age and that this dosage regimen should be used in young children in whom whole-virus vaccines are unacceptably reactive.

Reactions and serologic responses after administration of inactivated monovalent influenza A/swine virus vaccines. II. Immunization of children with influenza A/New Jersey/X-53 virus vaccines.

Reactivity and immunogenicity of two inactivated, zonally purified, ether-extracted, influenza A/New Jersey/X-53 subunit virus vaccines were studied in 103 children three to 18 years of age. Children aged nine years of younger received doses of 100 or 200 chick cell-agglutinating (CCA) units, and those older than nine years received doses of 200 or 400 CCA units. Vaccines were given intramuscularly. Two doses were given at intervals of four weeks. The vaccines were minimally pyrogenic, causing only two instances of temperatures of greater than 100.0 F. Other systemic reactions were observed infrequently. Tenderness at the site of injection occurred relatively frequently but was of no medical consequence. The geometric mean titers of homologous antibody, which ranged from 1:52 to 1:75 after administration of two doses, were statistically equivalent in all treatment groups. Titers of antibody of greater than or equal to 1:40 to the influenza A/New Jersey/8/76 virus strain were achieved by 88% of the vaccinees. We concluded that two doses of ether-extracted, subunit influenza A/New Jersey/X-53 virus vaccine were well tolerated and, when given at least four weeks apart, were serologically effective for immunization of children aged three to 18 years.

Relevance of the immunoprecipitation assay to human immunogenicity of influenza vaccines.

Influenza vaccines representing each of the four U.S. manufacturers' output for the 1975-76 respiratory season were characterized clinically and assayed by immunoprecipitation. All vaccines contained 350 CCA units/dose each of the A/Port Chalmers/1/73 (H3N2) and A/Scotland/840/74 (H3N2) viruses plus 550 CCA units/dose of B/HK/5/72 virus. Two of the vaccines were whole virus while the other two were subunit products; one made by extraction with ethyl ether, the second by detergent treatment. The vaccines were compared for serologic efficacy in children naturally primed to the (H3N2) family of viruses and by immunoprecipitation techniques against monospecific goat antiserum to the viral hemagglutinin prepared at the Bureau of Biologics of the U.S. Food & Drug Administration. The subunit vaccines had significantly greater specific activity (human immunogenicity/unit mass of type-specific precipitable antigen) than the whole virus products. It is concluded that clinical immunogenicity is as much a function of antigen form (subunit vs whole virus) as it is of mass and that setting a level for precipitable antigen content alone is an insufficient criterion for potency standardization. Since antigen form, as well as mass, must be considered, immunoprecipitation may be useful for standardization of human immunogenicity only if candidate lots are compared by this technique to an homologous, reference vaccine of identical manufacture and form which is tested for potency in humans.

Influenza immunization: clinical studies with ether-split subunit vaccines.

Clinical studies of ether-split influenza antigen vaccines have been in progress for almost a decade. One series of such studies, completed before the Hong Kong virus appeared, compared identically constituted conventional and antigen vaccines for serological effectiveness in 1700 vaccinees from the staff of a metropolitan hospital. A series of 6 annual trials included both "old" subjects (vaccinated the previous year) and "new" subjects (no vaccination the previous year). The serological response to the type A2 component of the antigen vaccines was 3-4 times better than that to intact virus in both the old and new populations. The response to either vaccine by new subjects significantly exceeded the response by the old subjects. The type B component of both vaccines induced an equivalent response in both populations. Monovalent Hong Kong vaccines, both conventional and antigen, given just prior to the Hong Kong epidemic induced an anamnestic response in a geriatric group. No influenza-like disease was seen in this high-risk group during the epidemic.