primary immunoglobulin generated after immunization, quickly followed by the IgG isotype. To demonstrate the immunogenicity of a vaccine, serum antivaccine (or antigenic marker) IgG antibodies are measured. For example, in studies of immunization with pandemic swine influenza A virus (H1N1) vaccines, detection of antibodies demonstrating inhibition of hemagglutination at a serum titer of 1:40 or greater provides evidence of seroprotection to the individual (Liang et al., 2010). These antibodies reduce infection by blocking the interaction between the influenza virus antigen, hemagglutinin, and cell surface receptors that it will use to enter the cell (Reddy et al., 2011). For the group of subjects studied, after a single immunization of 7.5 μg of a nonadjuvant split-virion formulation of the H1N1 vaccine in children ages 3 to <12 years, the increase in the hemagglutination titer over the baseline titer by 3 weeks postimmunization was robust (from a baseline mean titer of 6 to a postimmunization titer of 178) (Liang et al., 2010). When the titers are presented as geometric means to account for the distribution of responses, the baseline geometric mean titer was 5.3 and the postimmunization geometric mean titer was 178, a 32-fold response achieved by 3 weeks postimmunization. In adolescents (individuals ages 12 to <18 years), the geometric mean titers increased even more over the first 3 weeks postimmunization, from a baseline of 7 to 578, an 82-fold change (Liang et al., 2010).

The response to vaccination can be blunted in individuals who lack critical components of the immune system. For example, the responses to influenza immunization can be nonexistent or poor in patients who have received rituximab, which is an antibody to CD20, a membrane surface marker on B cells, present from early to full maturation of B cells and plasma cells, which secrete immunoglobulins (Bedognetti et al., 2011). Rituximab is useful therapeutically for the treatment of multiple conditions, including forms of lymphoma and collagen vascular diseases. However, the number of B (CD19+) cells can be reduced for 6 months or longer after discontinuation of rituximab in patients who are in remission from lymphoma. Treatment with rituximab was found to greatly reduce the number of memory B cells characterized as CD27+ and was associated with a poor or absent response to influenza immunization (Bedognetti et al., 2011). Although the patients had detectable CD4+ and CD8+ lymphocytes, they did not have CD19+ B cells and did have reduced numbers of CD27+ memory B cells, a condition which was associated with failure to mount a protective response after immunization (Bedognetti et al., 2011).

Another factor used to determine where a vaccine appears in the immunization schedule is vulnerability to the vaccine-preventable disease by age. This determination requires some knowledge of the pattern of disease in the community, which may differ by region of the world. As the immunity afforded by maternal antibodies at birth wanes, infants become



The National Academies | 500 Fifth St. N.W. | Washington, D.C. 20001
Copyright © National Academy of Sciences. All rights reserved.
Terms of Use and Privacy Statement