No abstract

Placental malaria (PM) can lead to poor neonatal outcomes, including low birthweight due to fetal growth restriction (FGR), especially when associated with local inflammation (intervillositis or IV). The pathogenesis of PM-associated FGR is largely unknown, but in idiopathic FGR, impaired transplacental amino acid transport, especially through the system A group of amino acid transporters, has been implicated. We hypothesized that PM-associated FGR could result from impairment of transplacental amino acid transport triggered by IV. In a cohort of Malawian women and their infants, the expression and activity of system A (measured by Na+-dependent 14C-MeAIB uptake) were reduced in PM, especially when associated with IV, compared to uninfected placentas. In an in vitro model of PM with IV, placental cells exposed to monocyte/infected erythrocytes conditioned medium showed decreased system A activity. Amino acid concentrations analyzed by reversed phase ultra performance liquid chromatography in paired maternal and cord plasmas revealed specific alterations of amino acid transport by PM, especially with IV. Overall, our data suggest that the fetoplacental unit responds to PM by altering its placental amino acid transport to maintain adequate fetal growth. However, IV more profoundly compromises placental amino acid transport function, leading to FGR. Our study offers the first pathogenetic explanation for FGR in PM.

The threat of novel influenza infections has sparked research efforts to develop subunit vaccines that can induce a more broadly protective immunity by targeting selected regions of the virus. In general, subunit vaccines are safer but may be less immunogenic than whole cell inactivated or live attenuated vaccines. Hence, novel adjuvants that boost immunogenicity are increasingly needed as we move toward the era of modern vaccines. In addition, targeting, delivery, and display of the selected antigens on the surface of professional antigen‐presenting cells are also important in vaccine design and development. The use of nanosized particles can be one of the strategies to enhance immunogenicity as they can be efficiently recognized by antigen‐presenting cells. They can act as both immunopotentiators and delivery system for the selected antigens. This review will discuss on the applications, advantages, limitations, and types of nanoparticles (NPs) used in the preparation of influenza subunit vaccine candidates to enhance humoral and cellular immune responses.

Placental malaria, especially when complicated with intervillositis, can cause fetal growth restriction. Transplacental glucose transport by glucose transporter isoform 1 (GLUT-1) on the syncytiotrophoblast microvillous and basal plasma membranes regulates fetal growth. We found that GLUT-1 expression in the microvillous plasma membrane of Plasmodium falciparum-negative placenta biopsy specimens was comparable to that in P. falciparum-positive placenta biopsy specimens with or without intervillositis, whereas GLUT-1 expression in the basal plasma membrane was lowest in P. falciparum-positive placenta biopsy specimens with intervillositis, compared with the other 2 specimen types (P ≤ .0016). GLUT-1 expression in the basal plasma membrane also correlated negatively with monocyte infiltrate density (r = -0.43; P = .003) and positively with birth weight (r = 0.28; P = .06). These findings suggest that intervillositis, more than placental malaria per se, might cause fetal growth restriction, through impaired transplacental glucose transport.