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Transcriptomic analysis whole blood single innate immune cells for analysis of of Tdap-IPV immune responses

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE195626 | GEO | 2024/01/22

REPOSITORIES: GEO

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Project description:The COVID-19 pandemic has prompted vaccine development efforts on an unprecedented scale. Vaccines based on mRNA technology have emerged as particularly attractive due to their high efficacy and short development timelines. However, relatively little is known about the factors contributing to the development of protective immunity by this new class of vaccines. We employed a high-temporal-resolution transcriptome profiling approach to investigate responses to COVID-19 mRNA vaccination. A cohort of 23 subjects was recruited and changes in blood transcript abundance were measured daily for 9 days post-priming and post-booster vaccination via RNA sequencing. Antibody responses were measured on days 7 and 14 post-vaccination using a custom multiplex assay. Marked differences were observed between responses to the priming and booster doses, with the latter inducing widespread changes in blood transcript abundance consistent with those found in patients with acute viral respiratory infections. The delineation of interferon responses at a high-temporal frequency also suggested that the priming and booster doses elicited distinct types of responses that peaked on day 2 post-priming dose and day 1 post-booster dose. The booster dose also induced inflammation on day 1 and erythroid cell signatures as well as an atypical plasmablast signature on day 4. Notably, this plasmablast signature, together with the post-booster interferon response signature, correlated with the antibody response levels induced on day 14 after the booster dose. Taken together, this work provides a detailed map of the antibody and transcriptional responses to the first and second doses of a new class of vaccine and yields important insights into the mechanisms underlying their immunogenicity. Furthermore, our results suggest that implementing high-temporal-frequency immune profiling protocols may provide an opportunity to better resolve the immune responses elicited by the growing number of available COVID-19 vaccines.

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.

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Transcriptomic analysis whole blood single innate immune cells for analysis of of Tdap-IPV immune responses

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