Author
HUDA, NAZMUL - University Of California, Davis | |
AHMAD, SHAIKH - International Centre For Diarrhoeal Disease Research | |
ALAM, MOHAMAD - International Centre For Diarrhoeal Disease Research | |
KHANAM, AFSANA - International Centre For Diarrhoeal Disease Research | |
KALANETRA, KAREN - University Of California, Davis | |
TAFT, DIANA - University Of California, Davis | |
RAQIB, RUBHANA - International Centre For Diarrhoeal Disease Research | |
UNDERWOOD, MARK - University Of California, Davis | |
MILLS, DAVID - University Of California, Davis | |
Stephensen, Charles |
Submitted to: Pediatrics
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 1/23/2019 Publication Date: 1/23/2019 Citation: Huda, N., Ahmad, S.M., Alam, M.J., Khanam, A., Kalanetra, K.M., Taft, D.H., Raqib, R., Underwood, M.A., Mills, D.A., Stephensen, C.B. 2019. Bifidobacterium abundance in early infancy and vaccine response at 2 years of age. Pediatrics. 143(2):e20181489. Interpretive Summary: Vaccination of young infants is an important public health strategy to decrease the risk of illness and death from common childhood infections. However, the immune system of young infants is immature and response to immunization can be quite variable in early infancy. Breastfeeding in early infancy can influence development of the infant immune system by a variety of mechanisms, including promotion of intestinal colonization with health-promoting commensal bacteria, such as Bifidobacterium longum. High-level colonization with such bacteria in early infancy, when infants receive many vaccines (including polio and tetanus vaccines), may affect development of the immune system and thus enhance response to these vaccines. This paper reports on the results of a collaborative research project between ARS scientists and colleagues that evaluated the association of intestinal colonization with Bifidobacterium in early infancy (below four months of age) with the magnitude of the response measured between 2 and 3 y of age. The study involved 306 breastfed infants born in Dhaka, Bangladesh who received their full course of vaccinations between birth and 4 months of age. The vaccine responses were measured shortly after vaccination, and again between 2 and 3 y of age. Infants with higher levels of colonization with Bifidobacterium had higher antibody and T-cell responses to the tetanus, polio and other vaccines. These findings suggest that strategies to enhance infant colonization with Bifidobacterium in early infancy will enhance response to vaccines given during early infancy, and may thus also decrease the risk of morbidity and mortality that may result from sub-optimal response to vaccination. Technical Abstract: Background: Vaccination in early infancy protects against many childhood diseases but vaccine efficacy is variable due, in part, to immaturity of the infant immune system. Maturation of the immune system is promoted by commensal bacteria, including bifidobacteria, that colonize the gut in early infancy. We hypothesized that a high abundance of bifidobacteria in early infancy would be positively association with memory responses to vaccines of early infancy when measured later in life, at 2 y of age. Methods: This observational study included 291 healthy Bangladeshi infants who received BCG (Bacillus Calmette–Guérin), OPV (oral polio virus), TT (tetanus toxoid), and HBV (hepatitis B virus) vaccines between birth and 14 w of age (NCT01583972, NCT02027610). Bifidobacterium in stool was measured at 6, 11 and 15 w. Bifidobacterium species and subspecies were measured at 6 w. Vaccine-specific CD4 T-cell and antibody responses were measured at 6 w, 15 w and 2 y. Results: Mean Bifidobacterium abundance in early infancy was positively associated with the CD4 T-cell responses to BCG, TT and HBV at 15 w, with CD4 T-cell responses to BCG and TT at 2 y, and with plasma TT-specific IgG and stool polio-specific IgA at 2 y. Similar associations were seen for B. longum subsp. infantis measured at 6 wk of age. Conclusions: Higher Bifidobacterium abundance may enhance responses to vaccines administered during early infancy. |