A graded-dose study of inactivated, surface antigen influenza B vaccine in volunteers: reactogenicity, antibody response and protection to challenge virus infection

Abstract

SUMMARYOne hundred and nineteen volunteers were divided into five groups, and each volunteer inoculated subcutaneously with an aqueous subunit B/Hong Kong/73 vaccine containing 40, 20, 10, or 5 ,ug of HA or saline alone in a 0-5 ml volume. The incidence of reactions was recorded 24 h after inoculation. One month following immunization the serum HI antibody to B/Hong Kong/73 virus was measured; each volunteer was inoculated intranasally with live, attenuated influenza B (RB77) virus; and the incidence of infection by the challenge virus was determined by HI antibody response.The results showed that the incidence of reactions to all doses of vaccine were relatively low, the severity mild, and the duration short. However, the incidence of reactions was highest for those given 40 jug HA and least for those given 5 4g HA. The serum HI antibody responses to vaccine showed a dose-response relationship. For volunteers given 40 jug HA, 22 (96 %) showed a fourfold rise in antibody titre and all volunteers had antibody titres of > 40 following immunization: for volunteers given 5 ,ug HA the g.m.t. increased from 16-6 to 86-1; and for those given 10 and 20,sg HA the response was intermediate. Following challenge, the lowest incidence ofinfection was seen in volunteers given the highest dose of vaccine. However, all doses of vaccine induced some protection against challenge virus infection, and the incidence of infection was directly related to the serum antibody titre at the time of challenge. The 50 % protection titre of serum HI antibody was estimated as 15 to 20.

Protection Against Influenza After Annually Repeated Vaccination

“…7 Challenge studies in healthy children and young adults have es- tablished that a high serum antibody level can prevent infection. [12][13][14] It has, therefore, been widely accepted as a surrogate marker for protection against influenza and vaccine efficacy in serologic studies.…”

Live, attenuated influenza virus (LAIV) vehicles are strong inducers of immunity toward influenza B virus

“…Historical analysis of influenza B virus vaccines in IIV form delivered either alone [16;64] or as part of a trivalent preparation [3;6;30;65;66] have demonstrated reduced immunity compared to similar formulations of influenza A virus components. Furthermore, Ohmit et al [32] recently demonstrated reduced efficacy and effectiveness toward the B virus component of a trivalent vaccine delivered in LAIV form.…”

“…Thus, it is difficult from the results reported thus far from these studies to decide how much of the perceived poor efficacy of vaccines for B vs. A is related to strain mis-match and how much is due to decreased immunogenicity. An added confounder is that protection against influenza B virus can be achieved with less than the 1:32 HI titer currently used to correlate with effective protection against influenza A viruses of the H1N1 and H3N2 subtypes [64;66,6870]. These factors and our data suggest that, contrary to current practice, utilizing analogous production techniques and correlates of immunity for both influenza A and B virus vaccines, as well as incorporating only a single strain each year, yields less than optimal immunity.…”

Isolation and studies of myxovirus glycoproteins

“…One line of evidence shows that isolated glycoproteins are unable to induce the formation of high antibody titres as determined in HI-test and neuraminidase reaction (10, 16) and in addition it was reported that subunit vaccines are unable to induce cell-mediated immunity (1t). Another line of evidence, however, shows that isolated glycoproteins induce both humoral and cell-mediated immunity and protection against the infection (7). A number of authors emphasize the critical importance of the presentation of the glycoproteins used, and associate a poor immune response with inadequate antigen presentation.…”