Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-γ (IFN-γ) producing spot-forming cells (SFC) to tetanus toxoid 2–3 months later. The frequency of IFN-γ producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-γ+/tumor necrosis factor-α (TNF-α)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later.

Dengue virus (DENV) infections range from asymptomatic or mild illness to a severe and potentially life threatening disease, dengue hemorrhagic fever (DHF). DHF occurs in primary DENV infections during early infancy. A prospective clinical study of DENV infections during infancy was conducted in San Pablo, Philippines. We found that infants who developed DHF with a primary DENV infection had higher WHO weight-for-age z scores before and at the time of infection compared to infants with primary DENV infections who did not develop DHF. In addition, TLR 7/8-stimulated tumor necrosis factor-α (TNF-α) production from myeloid-derived cells was higher among well-nourished infants. Leptin augmented TLR 7/8-mediated TNF-α production in monocytes and decreased intracellular cAMP levels. Circulating leptin levels were elevated during early infancy and correlated with WHO weight-for-age z scores. Our data support a plausible hypothesis as to why well-nourished infants are at risk for developing DHF with their first DENV infection.

Dengue is the most prevalent arthropod-borne viral illness in humans. A MHC class I polypeptide-related sequence B (MICB) single nucleotide polymorphism (SNP) was previously associated with symptomatic dengue compared to non-dengue causes of acute febrile illnesses in infants. We measured circulating levels of soluble (s)MICB in the sera of infants with symptomatic primary dengue virus infections. We found that serum levels of sMICB increased between pre-infection and acute illness among infants with symptomatic primary dengue virus infections. The likelihood of being hospitalized with an acute primary DENV infection during infancy also tended to be higher with increasing acute illness sMICB levels. The elevation of sMICB during acute primary DENV infections in infants likely represents an immune evasion strategy and contributes to the severity of the acute illness.

Dengue is the most prevalent arthropod-borne viral illness in humans. The current gold standard serologic test for dengue virus (DENV) infection is a neutralizing antibody assay. We examined a DENV recombinant (r)E protein domain III IgG ELISA among infants with primary DENV infections. Infants experience a primary DENV infection in the presence of maternally-derived anti-DENV IgG. The estimated DENV rE protein domain III IgG levels to the infecting serotype at the time of infant primary symptomatic DENV2 and DENV3 infections correlated with the 50% plaque reduction neutralization reciprocal antibody titers (PRNT50). Anti-DENVs 1–4 rE protein domain III IgG levels all correlated with each other, and the estimated rE protein domain III IgG level to the infecting serotype at the time of infection inversely correlated with dengue disease severity. The anti-DENV rE protein domain III IgG ELISA may be a useful and potentially high-throughput alternative to traditional DENV neutralizing antibody assays.

Human breast milk is known to contain immunoprotective, antimicrobial, and anti-inflammatory agents. In a prospective clinical study of dengue virus infections during infancy, we examined the correlation between breastfeeding and the development of febrile illnesses in an infant population. We found that breastfeeding status and the frequency of breastfeeding during early infancy was associated with a lower incidence of febrile illnesses.