1BCD). while lower but comparable median IgA and neutralizing titers were detected in breast milk from Korean and Vietnamese women, and the lowest titers were seen in American women. Neutralizing activity was greatest against the 2 2 vaccine strains of human origin, RV1 and 116E. This neutralizing activity in one half of the breast milk specimens from Indian women could reduce the effective titer of RV1 by ~2 logs, of 116E by 1.5 logs, and RV5 G1 strain by ~1 log more than that of breast milk from American women. Interpretation The lower immunogenicity and efficacy of rotavirus vaccines in poor developing countries could be explained, in part, by higher IPI-145 (Duvelisib, INK1197) titers of IgA and neutralizing activity in breast milk consumed by their infants at the time of immunization that could effectively reduce the potency of PRDM1 the vaccine. Strategies to overcome this negative effect, such as delaying breast-feeding at the time of immunization, should be evaluated. = 0.005) and the maximum difference in median titer was about 4-fold. Open in a separate window FIGURE 1 Cumulative frequency profiles of rotavirus-specific antibodies in breast milk specimens from mothers in India, Vietnam, Korea and the United States. Milk specimens were tested for IgA (A) and neutralizing activity against vaccine strains Rotarix (B), RotaTeq G1 (C), and 116E (D) as described in the text. Nearly all Indian women had an IgA titier 16 versus all other women. The median IgA and neutralizing titers and the distribution of titers for breast milk from Indian women were higher than all others. The values of significance between Indian women and those from Korea, Vietnam, and the United States are indicated. NA indicates neutralizing antibody. We then measured neutralizing activity in breast milk against 3 rotavirus vaccine strains RV1, RV5 G1 and 116E (Figs. 1BCD). Against RV1 (Fig. 1B), breast milk titers from the Indian women were significantly greater than those of all other women; 50% had high levels (64) of neutralizing activity and 30% had a titer 128. By contrast, titers in Vietnamese and American mothers (median, 1:2) were significantly lower than the others, and titers of Korean women (median, 1:8) were intermediate. Breast milk of Indian women also had the highest neutralizing titers against RV5 G1 and 116E strains, followed by milk from Korean and Vietnamese women (Figs. 1C, D). Mothers in the United States had low or no neutralizing activity against RV5 G1 and 116E. Of note, the greatest difference in median neutralization IPI-145 (Duvelisib, INK1197) titer between Indian and American mothers occurred in the human vaccine strains RV1 (median difference 32-fold) and 116E (16-fold) versus the RV5 G1 strain (~8-fold). Finally, we selected breast milk specimens with low (8) and high (256 C2048) neutralizing titers from India and those with no (2) and high (8 C32) titers from the United States to determine how much these samples could reduce the titer of RV1 by using a plaque reduction assay (Fig. 2). Except for some nonspecific reduction observed at the 1:8 dilution, low titer milk specimens from both India and USA did not substantially reduce the titer of the vaccine virus (Figs. 2A, C). However, all but one specimen of high titer milk from India and the United States resulted in a reduction in the titer of RV1. Furthermore, the magnitude of IPI-145 (Duvelisib, INK1197) reduction was dependent upon the level of IPI-145 (Duvelisib, INK1197) neutralizing activity in the specimens (Figs. 2B, D). For example, at a 1:32 dilution, all 6 Indian specimens resulted in 70% reduction in titer, whereas only 2 of 5 specimens from.