Ballas has consulting arrangements with Novartis DSMB (National Institute of Allergy and Infectious Diseases) and has received research support from Talecris Biotherapeutics, VA Merit Review, and the National Institutes of Health. of a 4-fold or greater antibody response. == Results == Per serotype, 10% to 40% of Mouse monoclonal antibody to eEF2. This gene encodes a member of the GTP-binding translation elongation factor family. Thisprotein is an essential factor for protein synthesis. It promotes the GTP-dependent translocationof the nascent protein chain from the A-site to the P-site of the ribosome. This protein iscompletely inactivated by EF-2 kinase phosporylation subjects with a high preimmunization titer attained at least a 4-fold response to vaccination. However, the odds of a 4-fold or greater response were found to decrease as a function of the absolute preimmunization titer value with an absolute value for each serotype beyond which the odds ratio approached zero. == Conclusion == High pneumococcal preimmunization titers do not necessarily preclude a 4-fold or greater response to vaccination. However, there appear to be serotype-specific preimmunization titer values, ranging from 4.4 to 10.3 g/mL, above which a 4-fold or greater response would not be expected. This response does not seem to be significantly affected by age, sex, IgG level, or IgG subclass value. Keywords:Pneumococcal vaccine, antibody, high preimmunization titer, fold response, age, sex, IgG, IgG subclass Specific antibody deficiency is defined as an abnormal antibody response to polysaccharide antigens in the context of normal serum immunoglobulin concentrations.1,2A vaccine containing polysaccharide antigens is administered, most commonly the un-conjugated 23-valent pneumococcal vaccine, to evaluate a patient suspected of having this immunodeficiency. Paired blood samples (before and after immunization) at least 4 weeks apart are drawn for evaluation of the IgG antibody response to each serotype. Depending on the laboratory used, various numbers of pneumococcal serotypes are evaluated. Although no definitive data are available, the recommendation of NNC 55-0396 an expert panel is that an adequate response to 50% or 70% of serotypes tested is a normal response for children or adults, respectively.1,3 On an individual serotype basis, an adequate response is defined as a 4-fold or greater increase over baseline NNC 55-0396 (ratio of postimmunization titer to preimmunization titer) or a postimmunization titer value of 1 1.3 g/mL or greater.1The 4-fold or greater increase as a requirement for an adequate response is based on the recommendation of the expert panel referenced above.1This recommendation was recently validated in a population of HIV-infected children.3The requirement that the postimmunization titer be 1.3 g/mL or greater is based on the fact that this level is thought to be protective against infection withStreptococcus pneumoniae.1,4,5 Interpretation of the antibody response to the 23-valent pneumococcal vaccine is straightforward if the preimmunization titer for a given serotype is less than 1.3 g/mL and the postimmunization titer is 1.3 g/mL or greater. Interpretation of the antibody response when the preimmunization titer for a given serotype is already 1.3 g/mL or greater is more controversial. One could argue that because the preimmunization titer is protective, the response to vaccination for that serotype is irrelevant. However, this ignores the purpose of vaccination in this case, which is to determine whether the immunologic machinery necessary for the response to polysaccharide antigens NNC 55-0396 is currently intact. The issue is not whether the titer is protective but whether one can use the data to evaluate the current ability to mount an antibody response. This is seen in adult patients with HIV who have protective titers but whose ability to respond to new antigens decreases as their CD4 T-cell counts decrease.6-8The debate then focuses on whether, for serotypes with preimmunization titers of 1 1.3 g/mL or greater, one should expect a 4-fold or greater response to vaccination. In this retrospective analysis we examined the antibody response to the unconjugated 23-valent pneumococcal vaccine in our patient population. For preimmunization titers NNC 55-0396 of 1 1.3 g/mL or greater, we looked at whether there is a relationship between absolute preimmunization titer value and the likelihood of a 4-fold or greater response. Our hypothesis was that a high preimmunization titer (1.3 g/mL) for a given serotype need not preclude a 4-fold or greater response to vaccination. We also examined whether the likelihood (odds) of obtaining a 4-fold response for preimmunization titers of 1 1.3 g/mL or greater was affected by factors such as age, sex, IgG level, or IgG subclass value. This study was focused on assessing the antibody response to the 23-valent pneumococcal vaccine as a function of preimmunization titer value; it was not intended to answer.
Ballas has consulting arrangements with Novartis DSMB (National Institute of Allergy and Infectious Diseases) and has received research support from Talecris Biotherapeutics, VA Merit Review, and the National Institutes of Health
