Given that PRV is an oral vaccine, these results likely reflect that, in developing countries, oral vaccines have a history of being less immunogenic than in the developed world. These differences of oral vaccines have been
postulated due to differences in the level of transplacentally acquired maternal antibody, immune and non-immune components of breast milk, the amount of gastric acid in the digestive tract, micronutrient malnutrition, interfering gut flora, and diarrheal and immune system disease , ,  and . In the case of Bangladesh versus Vietnam, the reasons for the decreased RAD001 clinical trial immunogenicity of PRV in Bangladeshi infants may be due to a combination of the differences in host populations and their associated health conditions, which include malnutrition Metabolism inhibitor and concomitant infections of the gut with several enteropathogens. In addition, the PD3 anti-rotavirus IgA GMT levels were also reduced in Asian subjects when compared to those of subjects in developed world
countries , , , , ,  and . The GMT (69.3 dilution units/mL) of the serum anti-rotavirus IgA at PD3 of Asian subjects was approximately 2-fold lower than those measured 14 or 42 days after Dose 3 in subjects in developed countries. However, once again, the pattern was not the same when the two countries were evaluated separately. The GMT level of the serum anti-rotavirus
IgA at PD3 of Bangladeshi subjects was 29.1 dilution units/mL, approximately 5- to 10-fold lower than those measured 14 or 42 days after Dose 3 in subjects in developed countries, while the PD3 GMT level of the serum IgA in Vietnamese subjects (158.5 dilution units/mL) was approximately the same as those measured 14 or 42 days after Dose 3 in subjects in the EU and Latin America  and . The clinical significance of these observations is not understood because an immune correlate of TCL protection has not been established. SNA responses to each of the five human serotypes, G1, G2, G3, G4, and P1A, contained in PRV were also evaluated at pD1 and PD3 in Asian subjects. The results showed a ≥3-fold rise in SNA responses to rotavirus serotypes G1, G2, G3, G4 and P1A in varying percentages in the Asian subjects. A consistent and similar pattern was observed when the data from Bangladesh and Vietnam were compared to those of the African subjects  and . For serotypes G1, G2, G3, G4, and P1A, the ≥3-fold SNA response rates in Bangladeshi subjects were approximately 50, 30, 10, 35, and 40 percentage points, respectively, lower than those exhibited by subjects in the US, EU, Taiwan, Korea, and Latin America , , , , ,  and .