Impact of Helminth Infections during Pregnancy on Vaccine Immunogenicity in Gabonese Infants

Abstract

Helminth infections are common in sub-Saharan Africa. Besides direct clinical effects, a bias towards a T helper type 2 (Th2) cell immune response is observed. The consequences of parasite infection during pregnancy for the mother and particularly for the fetus and the newborn can be severe and may include impaired immune response during acute infection and vaccination. Here, we present data of immune responses to vaccines given within the expanded program on immunization (EPI) of infants born to helminth infected or non-infected mothers. The study was conducted in Lambaréné and surroundings, Gabon. Maternal helminth infection was diagnosed microscopically using the Kato-Katz method for soil-transmitted helminths (STH), urine filtration for Schistosoma haematobium infections and the saponin-based method for filarial infections. Plasma antibody levels to different vaccine antigens were measured in mothers and their offspring by enzyme-linked immunosorbent assay (ELISA) at different timepoints. We found 42.3% of the mothers to be infected with at least one helminth species. Significantly lower anti-tetanus toxoid immunoglobulin (Ig) G was detected in the cord blood of infants born to helminth infected mothers. Following vaccination, immune responses of the infants to EPI vaccines were similar between the two groups at nine and 12 months. Even though infection with helminths is still common in pregnant women in Gabon, in our setting, there was no evidence seen for a substantial effect on infants’ immune responses to vaccines given as part of the EPI.

Vaccine-Induced Cellular Immunity against Bordetella pertussis: Harnessing Lessons from Animal and Human Studies to Improve Design and Testing of Novel Pertussis Vaccines

“…‘In-utero priming’ was first proposed in neonates born to infected mothers, who are exposed to pathogens but uninfected themselves [ 246 , 248 ]. For example, infants of helminth-infected mothers are exposed to parasite-derived products that seem to cross the placenta and potentially prime or tolerate the fetal immune response to parasite-specific as well as unrelated antigens [ 249 , 250 ]. This early exposure may have long-term effects on the child’s immune system, including their CMI to pertussis childhood vaccines [ 249 ].…”

“…For example, infants of helminth-infected mothers are exposed to parasite-derived products that seem to cross the placenta and potentially prime or tolerate the fetal immune response to parasite-specific as well as unrelated antigens [ 249 , 250 ]. This early exposure may have long-term effects on the child’s immune system, including their CMI to pertussis childhood vaccines [ 249 ]. To date, however, there has been no robust, consistent evidence that vaccine-induced (including pertussis) immune responses of infants are strongly suppressed or affected by the helminth infection status of the mother [ 249 , 251 , 252 , 253 ].…”

“…This early exposure may have long-term effects on the child’s immune system, including their CMI to pertussis childhood vaccines [ 249 ]. To date, however, there has been no robust, consistent evidence that vaccine-induced (including pertussis) immune responses of infants are strongly suppressed or affected by the helminth infection status of the mother [ 249 , 251 , 252 , 253 ]. In fact, strongyloidiasis was associated with enhanced responses to PT [ 251 ].…”

“…Similarly, empiric treatment of mothers with antihelminths (e.g. albendazole or praziquantel) during pregnancy does not influence infant responses to pertussis or other EPI vaccines [ 249 , 251 , 252 , 253 ]. Other maternal infections, such as malaria or HIV, may also play a key role in eliciting immune dysfunction in young infants, particularly in LMICs [ 254 ].…”

Exploratory analysis of the effect of helminth infection on the immunogenicity and efficacy of the asexual blood-stage malaria vaccine candidate GMZ2

“…A recent study carried out on school-age children in rural area of Gabon showed an increased risk of P. falciparum infection due to STH in schistosomiasis-positive children [11]. Many studies have also been conducted to assess the effect of helminth infection on several commonly used vaccines [12][13][14][15][16][17][18], but little is known about their interaction with malaria vaccine candidates [19][20][21][22]. GMZ2, a malaria vaccine candidate, is a recombinant fusion protein with fragments of P. falciparum GLURP and MSP3 [23] that showed good immunogenicity when formulated with aluminum hydroxide (alum) [24][25][26] or Cationic Adjuvant Formulation 01 (CAF01) adjuvant [27].…”