Dataset Information

Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria.

ABSTRACT:

Background

In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive.

Methods

We enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania. We collected cord blood, measured antibodies to Plasmodium falciparum Schizont Egress Antigen-1 (PfSEA-1), and related these antibodies to the risk of severe malaria in the first year of life. In addition, we vaccinated female mice with PbSEA-1, mated them, and challenged their pups with P. berghei ANKA parasites to assess the impact of maternal PbSEA-1 vaccination on newborns' resistance to malaria.

Results

Children with high cord-blood anti-PfSEA-1 antibody levels had 51.4% fewer cases of SM compared to individuals with lower anti-PfSEA-1 levels over 12 months of follow-up (P = .03). In 3 trials, pups born to PbSEA-1-vaccinated dams had significantly lower parasitemia and longer survival following a P. berghei challenge compared to pups born to control dams.

Conclusions

We demonstrate that maternally-derived, cord-blood anti-PfSEA-1 antibodies predict decreased risk of SM in infants and vaccination of mice with PbSEA-1 prior to pregnancy protects their offspring from lethal P. berghei challenge. These results identify, for the first time, a parasite-specific target of maternal antibodies that protect infants from SM and suggest that vaccination of pregnant women with PfSEA-1 may afford a survival advantage to their offspring.

SUBMITTER: Kurtis JD

PROVIDER: S-EPMC6938209 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria.

Kurtis Jonathan D JD Raj Dipak K DK Michelow Ian C IC Park Sangshin S Nixon Christina E CE McDonald Emily A EA Nixon Christian P CP Pond-Tor Sunthorn S Jha Ambrish A Taliano Ross J RJ Kabyemela Edward R ER Friedman Jennifer F JF Duffy Patrick E PE Fried Michal M

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America 20190501 10

<h4>Background</h4>In holoendemic areas, children suffer the most from Plasmodium falciparum malaria, yet newborns and young infants express a relative resistance to both infection and severe malarial disease (SM). This relative resistance has been ascribed to maternally-derived anti-parasite immunoglobulin G; however, the targets of these protective antibodies remain elusive.<h4>Methods</h4>We enrolled 647 newborns at birth from a malaria-holoendemic region of Tanzania. We collected cord blood, ...[more]

PMID: 30165569

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Project description:Avian metapneumoviruses (aMPV) are a causative agent of turkey rhinotracheitis (TRT). Despite vaccination, cases of TRT outbreaks are frequently reported. Considering that there are aMPV-free areas, a part of turkey poults possess (MDA+) or do not possess (MDA-) maternally derived antibodies (MDA) in the first weeks of life, which is the time of TRT vaccination. Study was undertaken to establish the level of protection against homologue aMPV/A infection, in MDA+ and MDA- turkeys, vaccinated against TRT at the 0 or 14th d of life and infected 14 d later. With the use of ELISA test and qPCR techniques, we have established the level of immune system stimulation after the vaccination and how does it correlate with the level of protection against the aMPV infection. Vaccination of MDA+ turkeys (especially at 0 d of life) resulted in weaker IgA production in upper respiratory tract. In addition, we have demonstrated differences in both humoral and cell-mediated immunity stimulation after infection of vaccinated turkeys. Despite these differences, we have shown that all vaccinated birds were protected against the disease which was determined based on the clinical and histopathological scoring, as well as the level of aMPV/A replication and shedding. Nonvaccinated groups of turkeys displayed typical signs of TRT after infection which indicates that MDA alone are incapable of preventing the disease. Differences in TRT course were recorded between different age groups of nonvaccinated birds. Birds infected at the 28th d of life (especially MDA- birds) developed more severe signs, and the level of aMPV replication was higher than that in birds infected on the 14th d of life. Despite the minor role in alleviating TRT course, MDA seems not to interfere with the vaccination efficacy. It is hard to predict whether the observed immune system stimulation differences between MDA+ and MDA- birds after vaccination can influence the outcome of vaccination efficacy under the field conditions.

Project description:BackgroundStudies of the association between the level of anti-malarial antibody and protection from malaria infection can yield conflicting results if they fail to take into account differences in the malaria transmission rate. This can occur because high malaria exposure may drive high antibody responses, leading to an apparent positive association between immune response and infection rate. The neonatal period provides a unique window to study the protective effects of antibodies, because waning maternally-derived antibodies lead to different levels of protection with time.MethodsThis study uses data from two well-defined infant cohorts in Western Kenya with different burdens of malaria transmission. Survival models were used to assess how the magnitude of maternally derived malaria-specific IgG antibody (to 24 malaria antigens measured using Luminex beads) affected the time-to-first Plasmodium falciparum infection (detected by PCR). In addition, mathematical models were used to assess how the frequency of malaria infection varied between the cohorts with different exposure levels.ResultsDespite differences in underlying malaria incidence in the two regions, there was no difference in time-to-first malaria infection between the cohorts. However, there was a significant period of protection observed in children with high initial MSP1 (42 kDa fragment)-specific antibody levels, but this protection was not observed in children with low antibody levels. Children from the high transmission cohort had both longer initial periods of protection from malaria (attributable to higher initial antibody levels), but more rapid time-to-first-infection once malaria specific maternal antibodies declined below protective levels (attributable to higher exposure rates).ConclusionThis study demonstrates the complex interaction between passive (maternally-derived) immunity and the degree of malaria exposure in infants. Children from regions of high malaria transmission had higher levels of maternally-derived antibodies in early life, which led to a significant protection for several months. However, once this immunity waned, the underlying higher frequency of infection was revealed. A better understanding of the interaction between malaria exposure, immunity, and transmission risk will assist in identifying protective immune responses in P. falciparum infection.

Dataset Information

Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria.

Background

Methods

Results

Conclusions

Publications

Maternally-derived Antibodies to Schizont Egress Antigen-1 and Protection of Infants From Severe Malaria.

Similar Datasets

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