Project description:Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. We extracted RNA from blood samples before, and 6 weeks after, vaccination to analyse the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analysed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. We found very few transcripts to alter systematically. Those that did mainly belonged to the interferon (IFN) signalling pathway. We scrutinized this pathway as well as the interleukin pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. In conclusion, the transcriptome changes following DTP booster vaccination were subtle, but it is possible to identify sub groups that deviate from each other, mainly in the IFN response. Microarrays (Human Exon 1.0 ST Arrays (Affymetrix )) were used to compare the gene expression alteration following DTP-vaccination in 18-19 months old West African girls. The gene expression analysis was based on RNA from venous blood. The blood was drawn immediately before DTP-vaccination (baseline sample) and 6 weeks after (42 -50 days, post-vaccination sample) in a total of eight girls
Project description:Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. To investigate possible changes in gene expression after DTP vaccination, we identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. We extracted RNA from blood samples before, and 6 weeks after, vaccination to analyse the coding transcriptome in leukocytes using expression microarrays, and ended up with information from eight girls. The data was further analysed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. We found very few transcripts to alter systematically. Those that did mainly belonged to the interferon (IFN) signalling pathway. We scrutinized this pathway as well as the interleukin pathways. Two out of eight showed a down-regulated IFN pathway and two showed an up-regulated IFN pathway. The two with down-regulated IFN pathway had also down-regulated IL-6 pathway. In the study of networks, two of the girls stood out as not having the inflammatory response as top altered network. In conclusion, the transcriptome changes following DTP booster vaccination were subtle, but it is possible to identify sub groups that deviate from each other, mainly in the IFN response.
Project description:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, pertussis antibody levels decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which may be associated with humoral responses, we analyzed changes in gene expression.
Project description:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, both pertussis antibody levels and clinical protection decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which can be associated with humoral responses, we analyzed changes in gene expression.
Project description:Control of pertussis depends on primary vaccination of infants in combination with booster vaccination of children, adults, and recently also pregnant women. Tetanus-diptheria-acellular pertussis (Tdap) booster vaccines are frequently given in many countries and can be formulated with inactivated poliovirus (Tdap-IPV). Although Tdap-IPV provides clinical protection, both pertussis antibody levels and clinical protection decay shortly after vaccination. This highlights the need for a better understanding of the mechanisms of immunogenicity of aP-containing combination vaccines, which may explain the longevity of the antibody response to vaccination. In order to identify immune signatures that are induced by Tdap-IPV vaccination and which can be associated with humoral responses, we analyzed changes in gene expression.
Project description:Diphtheria, tetanus, and pertussis (DTP) are infectious diseases caused by toxin-producing bacteria that can be fatal, especially in children. Despite the availability of combined DTP vaccines for more than 60 years, a comprehensive understanding of how human antibodies respond to DTP vaccination, which helps further improve the vaccine remains elusive. Here, we aimed to characterize toxin-specific antibody repertoires following DTP vaccination. To this end, CD19+CD27+ antigen-experienced B cells obtained from four healthy donors 7-days post vaccination were sorted for toxin-binding and non-toxin-binding B cells, using each of the DTP recombinant toxins (DT, TT, and PT) as fluorescent bait. 10X single-cell immune profiling was then performed, followed by in silico antibody sequence clustering.
Project description:Vaccination in pregnancy is an effective tool to protect both the mother and infant. Vaccines against tetanus, pertussis and influenza are recommended for use in pregnancy and new vaccines with specific indications for pregnancy are in the clinical trials pipeline. However our understanding of the immune response to vaccination in pregnancy is incomplete. We compared the effect of pregnancy on early (24 hours) transcriptional responses to vaccination. Pregnant mice and women were immunised with Boostrix-IPV, a vaccine containing pertussis antigens.
Project description:Vaccination in pregnancy is an effective tool to protect both the mother and infant. Vaccines against tetanus, pertussis and influenza are recommended for use in pregnancy and new vaccines with specific indications for pregnancy are in the clinical trials pipeline. However our understanding of the immune response to vaccination in pregnancy is incomplete. We compared the effect of pregnancy on early (24 hours) transcriptional responses to vaccination. Pregnant mice and women were immunised with Boostrix-IPV, a vaccine containing pertussis antigens.
Project description:Background: Drugs given to treat cancer (chemotherapy) can weaken the human immune system. But it can also become weaker because of aging. Interleukin (IL)-7, a molecule produced naturally in the body, can help improve the function of the immune system. Researchers want to study the effects of IL-7 on immune system function in two different groups of older people. One group will be people who have received vaccines before IL-7. The other group will be people who have received Vaccines after IL-7.
Objectives: To evaluate the effect of IL-7 on the immune system responses to vaccines in older people following chemotherapy.
Eligibility: People at least 60 years of age who have recently finished chemotherapy for breast, colon, or bladder cancer.
Design:
* People in the study will be screened with a physical examination, medical history, and blood tests. Other screening tests, such as tumor imaging, may also need to be performed.
* Everyone will receive a series of five different vaccines commonly used to prevent diseases. We will compare the responses of people in Sequence 1 who will receive vaccines before IL-7 with the responses of people in Sequence 2 who received the same vaccines after IL-7.
* The vaccines will be given randomly in two Arms at different times.
* Arm 1: diphtheria and tetanus, polio, pneumonia (with two booster shots), hepatitis B (with two booster shots), and hepatitis A (with one booster shot),
* Arm 2: hepatitis A (with one booster shot), hepatitis B (with two booster shots), pneumococcal (with two booster shots), diphtheria and tetanus, polio, pneumonia (with two booster shots)
* There are 5 vaccines to be given to each subject, following one of two randomly assigned sequences of vaccine administration (Sequence 1 or Sequence 2).
* The first vaccine arm contains the two diphtheria protein containing vaccines tetanus and diphtheria (Td) and pneumococcal conjugate 13 (PCV13) and polio. The second vaccine arm contains the Hepatitis A and Hepatitis B vaccines. Subjects will either get tetanus, diphtheria, polio, and pneumonia vaccines before IL-7 therapy (Sequence 1) or hepatitis A and hepatitis B vaccines before IL-7 therapy (Sequence 2). The response to vaccines will be evaluated 4 weeks after vaccination. This will be followed by IL-7 therapy, then administration of the other group of vaccines. Therefore, subjects on both arms will receive the same set of vaccines, just at different times with respect to IL-7 therapy.
Project description:Short Description: This study contains 7 RRBS samples, including 3 ex vivo CD4+ Trm (2 x spleen and 1 x bone marrow) and 4 blood tetanus (TT) and measles (Me) antigen-reactive memory CD4+ cells before and one day post DTaP (diphtheria-tetanus-pertussis) and MMR (measles-mumps-rubella) vaccination, respectively (1 x tetanus D0, 1 x tetanus D1, 1 x measles D0, 1 x measles D1).
Technology: Illumina HiSeq 2500
Filetype: fastq format