Effect of Maternal Vitamin A Supplementation on Maternal Immune Response to Inactivated Influenza Vaccination, and on Passive Protection of Infants

Influenza morbidity affects the entire population and has an enormous impact upon the economic burden and the health care system, particularly causing serious illness among young infants 0-6 months of age. Recent studies show high rates of influenza illness and hospitalization among infants at this age group in industrialized countries (Chiu et al., 2002; Poehling et al., 2006) and influenza related childhood mortality is highest in young infants before 6 months of age (Bhat et al., 2005). Unfortunately, inactivated influenza vaccine is not recommended for this age group, but pregnant women can be vaccinated during 2nd - 3rd trimester. Thus the strategy of passive immunization (from mother) of infants is the effective way to combat this infection among young infants. This approach adopted in US since 1997 and recommended by WHO since 2005.

Upper respiratory tract is the portal of virus entry and primary site of replication (Gluck et al., 1994; Muszkat et al., 2000). Thus the importance of the presence of effective mucosal antibodies at the entry site of virus is essential to neutralize the virus and prevent infection (Meitin et al., 1994). Secretory IgA (sIgA) is the primary mucosal antibody, accounting for ~70% of the body's total antibody production (Brandtzaeg, 1994). sIgA has been shown to mediate nasal anti-influenza mucosal immunity (Renegar & Small, 1991) and therefore indicates the importance of vaccination strategies that trigger specific antibody production at mucosal surfaces as well as the importance of dietary nutrients to trigger the release of mucosal neuropeptides necessary for maintenance of the mucosal immune system (Renegar et al., 2001). A number of clinical trials examined the effect of vitamin A supplementation in humans on indicators of mucosal immunity. Supplementation to human immunodeficiency virus infected pregnant women is associated with improved gut permeability in their infants at 14 weeks as measured by lactulose/mannitol (L/M) urinary excretion test (Filteau et al., 1999). While vitamin A supplementation during pregnancy (Semba et al., 1999) or the early postpartum period (Filteau et al., 2001) show no effect on total sIgA in breast milk, rather vitamin A in milk has been shown to inhibit the growth of both enveloped and non-enveloped viruses (Clarke & May, 2000). However, total sIgA level of vitamin A-sufficient children has been detected significantly higher than that of vitamin A-deficient children (Lin et al., 2007). In animal model, vitamin A supplementation increases both total and antigen specific sIgA-containing cells in the mucosa, which in turn improves the survival rate (Nikawa et al., 2001) During early infancy breast milk is the predominant source of vitamin A and to date no study investigates the effect of prenatal vitamin A supplementation and vaccination on the vaccine specific mucosal sIgA responses in offspring. Although maternal IgA is not transplacentally transferred to the infants, but increased vitamin A and vaccine specific sIgA in breast milk as a result of maternal vitamin A supplementation may enhance infant's nasal sIgA responses that in turn may provide improved passive protection among young infants.

In our recent study (Mother'SGift Project, funded by Thrasher Research Fund), we have detected that maternal influenza vaccination can reduce influenza illness substantially in young infants up to 6 months of age in Bangladesh (Zaman et al., 2008). On the other hand the prevalence of vitamin A deficiency among pregnant women in Bangladesh as well as in other developing countries is very high. More than half of the pregnant women in Bangladesh consume less vitamin A than the recommended dietary allowance and have low vitamin A status (serum retinol <1•05 μmol/L) with approximately one-fifth of them classified as deficient (serum retinol <0•70 μmol/L) (Ahmed et al., 2003; Lee et al., 2008). Nonetheless, there is conclusive scientific evidence suggesting several aspects of both innate and adaptive immunity are compromised by clinical and subclinical vitamin A deficiency (Stephensen, 2001). In another study, we observed a significant positive association between primary yellow fever viral vaccine specific lymphocyte blastogenesis / antibody responses and body vitamin A store (Ahmad et al., 2008). Thus in view of the potential immune regulatory roles of vitamin A, it is of interest to investigate whether maternal vitamin A supplementation along with influenza vaccination could be used as public health intervention strategy to combat both influenza infection and vitamin A deficiency simultaneously among mothers and young infants in developing countries.

Research Design and Methods:

Study Site: This study will be carried out at ICDDR,B; Dhaka, Bangladesh. Three urban maternity clinics located at Mirpur area of Dhaka city will be selected for approaching mothers who visit the clinic in the first trimester and who are the residence of the nearby community.