We have previously shown that the generation of antibodies to a polysaccharide vaccine (Typhim Vi) is compromised in Pakistani adults born of a lower birth weight. To assess whether this represents a true B-cell-dependent deficit, we revaccinated subjects with a second dose of the same vaccine and with a polysaccharide-protein conjugate vaccine to a different polysaccharide antigen (conjugated Haemophilus influenzae type b (Hib) vaccine). Anti-Vi IgG levels remained positively correlated with birth weight (p=0.0284) but no associations were observed between anti-Hib IgG levels and size at birth. These findings indicate that small size at birth results in a poor antibody response to vaccination with a polysaccharide antigen vaccine in adulthood, even following a second dose of the vaccine. No such association was observed in response to a polysaccharide-protein conjugate vaccine indicating an early-life programming effect on the generation of antibodies during a B-cell-dependent immune response.