Immunity to hepatitis B in South African students following childhood vaccination

Abstract

In this empirical research, I discuss the long-term humoral and cellular immune response to childhood hepatitis B virus (HBV) vaccination among South African medical students. Healthcare workers (HCWs) are considered at a high risk of HBV exposure and have a four times greater probability of contracting the virus than the general population, simply because HCWs are exposed to blood and body fluids as well as needle stick and sharps injuries. The study was conducted in Bloemfontein where samples were collected at three different timepoints from 122 Central University of Technology (CUT) Biomedical and University of the Free state (UFS) medical students. Participants were South African students born during and after 1995 who had not been vaccinated at any point against HBV after their childhood vaccination. It took approximately 7 months to observe the response to the complete booster vaccination schedule. The first samples were obtained from February to March 2018. The second samples were obtained a month after the initial sampling, and the third samples 7 months after the initial blood draw. Students were also immunized at the first and second time point, with the last vaccination administered a month before the last blood draw (6 months after the initial vaccination) to adhere to a standard 0-, 1- and 6-month vaccination schedule. Information collected at the first time point included date of birth, age, gender, race, vaccination and clinical history. However, if this information was not available, it did not exclude the participant from the study. The baseline sample draw and first dose of immunizations were done at both institutions. The samples were drawn before vaccination so that the baseline HBsAb titre results reflected those obtained from childhood vaccination. Two blood samples were drawn, one without an anticoagulant (clotted tube) for serological tests and one lithium-heparinized tube to perform the interferon-gamma (IFN-y) and interleukin-2 (IL2) release assays. The second samples were collected one month after baseline sampling. One tube without anticoagulant (clotted tube) was taken at this time point for serological testing. The second shot of HBV vaccine was administered at this time point. Clotted blood samples were obtained again at the 7-month collection. Samples were collected in the same manner as previous collections; however, no vaccination was done at the 7-month interval. Vaccination was done at 6 months after baseline vaccination (a month before the 7-month blood draw), as it is recommended that immunity following HBV vaccination is tested approximately one month following the third dose. Samples were analysed for hepatitis B surface antibody (HBsAb), hepatitis B core antibody (HBcAb), interleukin 2 (IL-2) and interferon gamma (IFN-y). HBsAb and HBcAb tests were conducted on the Liaison® XL Murex instrument. The IFN-y and IL-2 were manual ELISA tests which were read on the Biotek-ELx800. At baseline, 52% tested negative for HBsAb, while 43% tested positive and 5% were equivocal. Following a single booster dose of HBV vaccine, 92% of participants showed adequate HBsAb responses. At the end of vaccinations, all participants tested positive for HBsAb. IFN-y results grouped and associated with baseline HBsAb results showed to be statistically not significant, while at second sampling these proved to be statistically significant, with a p value of 0.03. For IL-2, the association with both baseline and second sampling HBsAb proved to be statistically significant with a p-value of 0.02 at baseline and <0.01 at second sampling. Only one participant in this study provided childhood immunization records. The remainder were unaware of their vaccination status and did not have access to their childhood immunization records. This indicates the need for exploring alternative methods of documenting immunization in order to improve record keeping and provide better continuity of care. This vaccination programme is expected to provide long-term protection against HBV infection. However, more than half of the participants (52%) tested negative for HBsAb at baseline. This is suggestive of waning humoral immunity. Possible factors that could induce waning are weight, age and the type of vaccination administered. At second sampling, 92% of the participants tested positive to HBsAb. This indicates a strong anamnestic response and this is an indication that most participants have likely been vaccinated previously during childhood and have developed long-term memory immune responses. At baseline, the association between IL-2 results and HBsAb gave a p-value of 0.02 indicative of a statistically significant association. The sensitivity and specificity of IL-2 results to predict HBsAb status was 93% and 26%, respectively. IL-2 seemed to be a more reliable assay as it produced much higher results at baseline and during second sampling. The participants who tested positive had the highest median of 92pg/mL. After booster vaccinations, the sensitivity and specificity were 85% and 71%, respectively, with a p- value of >0.01. Participants who tested positive also had the highest median of 65 pg/mL. When comparing the two ELISA tests, we can confirm based on the sensitivity, specificity and p-value that IL-2 is a much more reliable marker to use in order to evaluate cellular immunity that has been induced by vaccination. This can be seen prior to and after booster vaccination. However, we cannot conclude the above, because there a high number of participants were involved during IL-2 testing; therefore, giving a much more accurate platform to make a conclusion. Both the IFN-y and IL-2 assays are involved in the cellular immune response. However, in this study, they were used as proxies for existing immunological memory. The immune system of the participants has been exposed previously to HBV antigens and this can be seen by the cytokines response when stimulated by the presence of antigens, which can either be through HBV infection or vaccination. It is recommended that HB booster vaccination be included in policies as part of a routine programme for all individuals, more especially, individuals in healthcare settings and other high-risk areas because of the waning immunity in more than half of the participants. IL-2 assay has proven to be a more reliable assay due to its high sensitivity and specificity; therefore, it can be implemented as one of the routine checks to use in order to assess cellular immunity that is induced due to vaccination. Only one participant produced his/her vaccination records for the use of the study, while the rest of the participants did not have their records available. Therefore, it is recommended that in future, more digital records should be used that will be accessible at all healthcare settings.