Dataset Information

Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response.

ABSTRACT: Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection.

SUBMITTER: Rinchai D

PROVIDER: S-EPMC5580375 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:One of the most common rabbits coccidia species, Eimeria magna is mainly parasitic in the ileal and jejunal epithelial cells. E. magna infection can affect the growth performance of rabbits or cause other secondary diseases. Traditional methods of anticoccidial treatment typically result in drug resistance and drug residue. Therefore, vaccination is a promising alternative. Gametocyte antigen 56 (GAM56) and rhoptry kinase family proteins (ROPs) are involved in oocyst wall formation and parasite invasion, respectively. A virulence factor, ROP17 contains a serine/threonine kinase catalytic domain. In this study, recombinant E. magna GAM56 (rEmGAM56) and ROP17 (rEmROP17) proteins were obtained from a prokaryotic expression system and their reactogenicity was investigated with immunoblotting. To assess the potential of rEmGAM56 and rEmROP17 as coccidiosis vaccines, New Zealand White rabbits were subcutaneously immunized with 100 μg rEmGAM56 (rGC group) or rEmROP17 (rRC group) twice at 2-week intervals followed by homologous oocyst challenge. The rabbit serum was collected weekly to detect the specific antibody levels. The cytokine levels of pre-challenge serum were measured by enzyme-linked immunosorbent assay and the rabbits were observed and recorded post-challenge for the onset of clinical symptoms. The weight gain, oocyst output, and feed conversion ratio were calculated at the end of the experiment. The results showed that both rEmGAM56 and rEmROP17 had good reactogenicity. The rEmGAM56- or rEmROP17-immunized rabbits had milder clinical symptoms and feed conversion ratios of 3.27:1 and 3.37:1, respectively. The rEmGAM56-immunized rabbits had 81.35% body weight gain and 63.85% oocyst output reduction; the rEmROP17-immunized rabbits had 79.03% body weight gain and 80.10% oocyst output reduction. The ACI of rGC and rRC groups were 162.35 and 171.03, respectively. The specific antibody levels increased rapidly after immunization. Significantly increased interleukin (IL)-2, interferon (IFN)-γ, and IL-17 levels were evident in the rGC and rRC groups (p < 0.05). The rEmGAM56 and rEmROP17 elicited humoral and cellular responses, which protected against E. magna infection in rabbits. Thus, rEmGAM56 and rEmROP17 are potential vaccine candidates against E. magna, and rEmROP17 performed better than rEmGAM56.

Project description:Avian infectious bronchitis virus (IBV) is the causative agent of infectious bronchitis, which results in considerable economic losses. It is imperative to develop safe and efficient candidate vaccines to control IBV infection. In the current study, recombinant baculoviruses co-expressing the S1 and N proteins and mono-expressing S1 or N proteins of the GX-YL5 strain of IBV were constructed and prepared into subunit vaccines rHBM-S1-N, rHBM-S1 and rHBM-N. The levels of immune protection of these subunit vaccines were evaluated by inoculating specific pathogen-free (SPF) chickens at 14 days of age, giving them a booster with the same dose 14 days later and challenging them with a virulent GX-YL5 strain of IBV 14 days post-booster (dpb). The commercial vaccine strain H120 was used as a control. The IBV-specific antibody levels, as well as the percentages of CD4+ and CD8+ T lymphocytes, were detected within 28 days post-vaccination (dpv). The morbidity, mortality and re-isolation of the virus from the tracheas and kidneys of challenged birds were evaluated at five days post-challenge (dpc). The results showed that the IBV-specific antibody levels and the percentages of CD4+ and CD8+ T lymphocytes were higher in the rHBM-S1-N vaccinated birds compared to birds vaccinated with the rHBM-S1 and rHBM-N vaccines. At 5 dpc, the mortality, morbidity and virus re-isolation rate of the birds vaccinated with the rHBM-S1-N vaccine were slightly higher than those vaccinated with the H120 control vaccine but were lower than those vaccinated with the rHBM-S1 and rHBM-N vaccines. The present study demonstrated that the protection of the recombinant baculovirus co-expressing S1 and N proteins was better than that of recombinant baculoviruses mono-expressing the S1 or N protein. Thus, the recombinant baculovirus co-expressing S1 and N proteins could serve as a potential IBV vaccine and this demonstrates that the bivalent subunit vaccine including the S1 and N proteins might be a strategy for the development of an IBV subunit vaccine.

Project description:Obesity is a risk factor for developing severe influenza virus infection, making vaccination of utmost importance for this high-risk population. However, vaccinated obese animals and adults have decreased neutralizing antibody responses. In these studies, we tested the hypothesis that the addition of either alum or a squalene-based adjuvant (AS03) to an influenza vaccine would improve neutralizing antibody responses and protect obese mice from challenge. Our studies demonstrate that adjuvanted vaccine does increase both neutralizing and nonneutralizing antibody levels compared to vaccine alone. Although obese mice mount significantly decreased virus-specific antibody responses, both the breadth and the magnitude of the responses against hemagglutinin (HA) and neuraminidase (NA) are decreased compared to the responses in lean mice. Importantly, even with a greater than fourfold increase in neutralizing antibody levels, obese mice are not protected against influenza virus challenge and viral loads remain elevated in the respiratory tract. Increasing the antigen dose affords no added protection, and a decreasing viral dose did not fully mitigate the increased mortality seen in obese mice. Overall, these studies highlight that, while the use of an adjuvant does improve seroconversion, vaccination does not fully protect obese mice from influenza virus challenge, possibly due to the increased sensitivity of obese animals to infection. Given the continued increase in the global obesity epidemic, our findings have important implications for public health. Vaccination is the most effective strategy for preventing influenza virus infection and is a key component for pandemic preparedness. However, vaccines may fail to provide optimal protection in high-risk groups, including overweight and obese individuals. Given the worldwide obesity epidemic, it is imperative that we understand and improve vaccine efficacy. No work to date has investigated whether adjuvants increase the protective capacity of influenza vaccines in the obese host. In these studies, we show that adjuvants increased the neutralizing and nonneutralizing antibody responses during vaccination of lean and obese mice to levels considered "protective," and yet, obese mice still succumbed to infection. This vulnerability is likely due to a combination of factors, including the increased susceptibility of obese animals to develop severe and even lethal disease when infected with very low viral titers. Our studies highlight the critical public health need to translate these findings and better understand vaccination in this increasing population.

Dataset Information

Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets