Measurement of Typhi Vi antibodies can be used to assess adaptive immunity in patients with immunodeficiency

Abstract

SummaryVaccine‐specific antibody responses are essential in the diagnosis of antibody deficiencies. Responses to Pneumovax II are used to assess the response to polysaccharide antigens, but interpretation may be complicated. Typhim Vi®, a polysaccharide vaccine for Salmonella typhoid fever, may be an additional option for assessing humoral responses in patients suspected of having an immunodeficiency. Here we report a UK multi‐centre study describing the analytical and clinical performance of a Typhi Vi immunoglobulin (Ig)G enzyme‐linked immunosorbent assay (ELISA) calibrated to an affinity‐purified Typhi Vi IgG preparation. Intra‐ and interassay imprecision was low and the assay was linear, between 7·4 and 574 U/ml (slope = 0·99–1·00; R 2 > 0·99); 71% of blood donors had undetectable Typhi Vi IgG antibody concentrations. Of those with antibody concentrations > 7·4 U/ml, the concentration range was 7·7–167 U/ml. In antibody‐deficient patients receiving antibody replacement therapy the median Typhi Vi IgG antibody concentrations were < 25 U/ml. In vaccinated normal healthy volunteers, the median concentration post‐vaccination was 107 U/ml (range 31–542 U/ml). Eight of eight patients (100%) had post‐vaccination concentration increases of at least threefold and six of eight (75%) of at least 10‐fold. In an antibody‐deficient population (n = 23), only 30% had post‐vaccination concentration increases of at least threefold and 10% of at least 10‐fold. The antibody responses to Pneumovax II and Typhim Vi® correlated. We conclude that IgG responses to Typhim Vi® vaccination can be measured using the VaccZyme Salmonella typhi Vi IgG ELISA, and that measurement of these antibodies maybe a useful additional test to accompany Pneumovax II responses for the assessment of antibody deficiencies.

The Expanding Field of Secondary Antibody Deficiency: Causes, Diagnosis, and Management

“…However, even in these newer, updated guidelines, there remains a paucity of recommendations related to the diagnosis and screening for secondary antibody deficiency or those addressing the treatment of secondary antibody deficiency specifically. As discussed above, vaccine-specific antibody response is a key tool in the diagnosis of secondary antibody deficiency that will benefit from new assays to assess responses to polysaccharide vaccination, such as Typhim Vi (typhoid polysaccharide vaccine, Sanofi Pasteur, UK), which are being increasingly introduced (240, 241). It will also be important to harness pharmacogenetics in patient selection and risk stratification.…”

From infections to autoimmunity: Diagnostic challenges in common variable immunodeficiency

“…The vaccination response in adults is satisfactory if at least 70% of the measured serotype-specific antibody titers are above 1.3 μg/mL or a four-fold increase of the pre-vaccination titers for more than 17 of 23 serotypes is observed at week 4 after immunization[ 59 ]. An alternative to PPV is the measurement of response after immunization against Salmonella typhi[ 60 , 61 ]. Isohemagglutinins are naturally occurring antibodies of IgM and IgG isotypes to polysaccharide blood group antigens.…”

Antibody deficiency testing for primary immunodeficiency

“…Therefore, patients receiving IVIG can receive vaccination and titers can be measured before and after to evaluate response, which has been studied by multiple groups and found to be reliable. [41][42][43] In 1 laboratory, less than a 2-fold increase between prevaccination and postvaccination titers had good diagnostic accuracy to identify patients with known humoral deficiencies. 42 Other vaccines can be used to assess neoantigen responses in vaccine-naïve patients.…”