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:Influenza immunization during pregnancy provides protection to the mother and the infant. Studies in adults and children with inactivated influenza vaccine (IIV) have identified changes in immune gene expression that correlated with antibody responses. We studied changes in transcriptional profiles induced by IIV in pregnant women and to identify correlates of antibody responses.
Project description:The gene expression in whole blood and simultaneous muscle biopsy (site of immunization and control contralateral non-injected leg) was measured in healthy adult male humans attending a research unit (CRC, University of Surrey, UK), who were randomized to receive a single immunization with an adjuvanted licensed vaccine or saline placebo control.
Project description:Aged patients suffer disproportionately increased morbidity and mortality associated with SARS-CoV-2 infection. Despite numerous clinically available vaccines and therapeutics, aged patients remain at increased risk for COVID-19 morbidity. Furthermore, the aged patient population has suboptimal responses to SARS-CoV-2 vaccine antigens. Here, we characterize vaccine-induced responses to SARS-CoV-2 synthetic DNA vaccine antigens in 18-month-old mice and interrogate protection. Aged mice have altered cellular responses, including decreased IFNγ secretion and increased TNFα secretion as compared to young mice. Aged mice had significantly decreased binding and neutralizing antibodies in their serum compared to their young counterparts. Co-immunization with the plasmid-encoded molecular adjuvant adenosine deaminase-1 (pADA) enhanced cellular responses and expanded the breadth of humoral responses in aged mice. pADA co-delivery also altered the gene expression profiles of lymph node lymphocytes in aged animals. Upon challenge pADA co-immunization modestly decreased age-associated morbidity and mortality in ACE2 transgenic and mouse-adapted SARS-CoV-2 challenge models. These data support the use of aged mice as a model for age-associated decreased vaccine immunogenicity and infection-mediated morbidity and mortality in the context of SARS-CoV-2 and provide further support of the use of adenosine deaminase as a molecular adjuvant.
Project description:Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide and causes respiratory disease, abortion, and in some cases, neurological disease. EHV-1 strain KyA is attenuated in the mouse and equine, whereas wild-type strain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb at 4 to 6 days post-infection. Our previous results showed that EHV-1 KyA immunization protected CBA mice from pathogenic RacL11 challenge at 2 and 4 weeks post-immunization, and that the infection with the attenuated KyA elicits protective humoral and cell-mediated immune responses. To investigate the protective mechanisms of EHV-1 KyA by innate immune responses, CBA mice immunized with live KyA were challenged with RacL11 at various times post-vaccination. KyA immunization effectively protected CBA mice from RacL11 challenge at 1 to 7 days post-immunization. Immunized mice lost less than 10% of their preinfection body weight and rapidly regained body weight. Lung virus titers in EHV-1 KyA-immunized CBA mice were 1,000-fold lower at 2 days post-RacL11 challenge than lungs of non-immunized mice, which was indicative of accelerated virus clearance. Affymetrix microarray analysis revealed that IFN-γ and 16 antiviral interferon-stimulated genes (ISGs) were upregulated 3.1- to 48.2-fold at 8 h post-challenge in the lungs of RacL11-challenged mice that had been immunized with KyA. Murine IFN-γinhibited EHV-1 infection of murine alveolar macrophage MH-S cells and effectively protected mice against lethal EHV-1 challenge, suggesting that IFN-γ expression may be important in mediating protection elicited by KyA immunization. These results suggest that EHV-1 KyA can be used as a live attenuated EHV-1 vaccine as well as a prophylactic agent in horses.
Project description:Intranasal (IN) immunization induces different genotype expression in CD8 memory T cells compared to the CD8 memory T cells induced by intramuscular (IM) immunization. We used microarrays to detail the global program of gene expression underlying the differential induction after IN or IM immunization.
Project description:Topical (epicutaneous, e.c.) application of the adjuvant CpG ODN during immunization leads to a robust immune response compared to when subcutaneous (s.c.) administration. Dendritic cells are hematopoietically derived cells that are important in cross-presenting to and activating CD8 T cells. Dermal dendritic cells are one of the two major dendritic cell subsets found in the skin which mobilize from the skin to draining lymph nodes to present to T cells upon activation. Dermal dendritic cells are found in skin draining lymph nodes around 24 hours post immunization. To determine how the immune system respond differently between e.c. versus s.c. administration of CpG ODN, we evaluated changes in the skin draining lymph node environment upon the two routes of adjuvant application. Expression chemokines and chemokine receptors were assessed with real-time qPCR. To determine the changes in the skin draining lymph node environment (cytokine and cytokine receptor levels) upon immunization via real time RT-PCR.
Project description:Ad26.COV2.S is a single-shot vaccine with clinical efficacy against symptomatic COVID-19. In this study, we report the correlates of durability of humoral and cellular immune responses in 20 rhesus macaques immunized with single-shot Ad26.COV2.S and the immunogenicity of a booster shot at 8-10 months following the initial immunization. Innate immune responses, memory B cell responses, and bone marrow plasma cell responses correlated with durable antibody responses following initial vaccination. Following Ad26.COV2.S boost immunization, binding and neutralizing antibody responses increased 31-69 fold and 23-43 fold, respectively, compared with pre-boost levels against multiple SARS-CoV-2 variants, including the delta variant. Antigen-specific B cell and T cell responses also increased. Humoral and cellular immune responses were largely comparable for ancestral, alpha, beta, gamma, delta, and kappa SARS-CoV-2 variants following the boost immunization. Boosting with a modified Ad26.COV2.S.351 vaccine expressing the SARS-CoV-2 beta Spike led to largely comparable responses. These data demonstrate that a late boost with Ad26.COV2.S in rhesus macaques resulted in a dramatic increase in humoral and cellular immune responses that were highly cross-reactive across multiple SARS-CoV-2 variants.