Subunit influenza vaccine candidate based on CD154 fused to HAH5 increases the antibody titers and cellular immune response in chickens

BCG is the only licensed vaccine against Mycobacterium tuberculosis (M.tb) infection. Due to its intramuscular administration route, BCG is unable to induce a local protective immune response in the respiratory system. Moreover, BCG has a diminished ability to induce long-lived memory T-cells which are indispensable for antituberculosis protection. Recently we described the protective efficacy of new mucosal TB vaccine candidate based on recombinant attenuated influenza vector (Flu/THSP) co-expressing TB10.4 and HspX proteins of M.tb within an NS1 influenza protein open reading frame. In the present work, the innate and adaptive immune response to immunization with the Flu/THSP and the immunological properties of vaccine candidate in the BCG-prime → Flu/THSP vector boost vaccination scheme are studied in mice. It was shown that the mucosal administration of Flu/THSP induces the incoming of interstitial macrophages in the lung tissue and stimulates the expression of co-stimulatory CD86 and CD83 molecules on antigen-presenting cells. The T-cellular immune response to Flu/THSP vector was mediated predominantly by the IFNγ-producing CD8+ lymphocytes. BCG-prime → Flu/THSP vector boost immunization scheme was shown to protect mice from severe lung injury caused by M.tb infection due to the enhanced T-cellular immune response, mediated by antigen-specific effector and central memory CD4+ and CD8+ T-lymphocytes.

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PBMC transcriptomic responses to primary and secondary vaccination differ due to divergent lean growth and antibody titers in a pig model

Physiological Genomics ◽

10.1152/physiolgenomics.00015.2015 ◽

2015 ◽

Vol 47 (10) ◽

pp. 470-478 ◽

Cited By ~ 3

Author(s):

Marcel Adler ◽

Eduard Murani ◽

Siriluck Ponsuksili ◽

Klaus Wimmers

Keyword(s):

Immune Response ◽

Cellular Immune Response ◽

High Performance ◽

Booster Vaccination ◽

Transcript Abundance ◽

Cell Receptor ◽

Growth Factor Signaling ◽

Lean Growth ◽

Antibody Titers ◽

Cellular Immune

The genetic relationship between immune responsiveness and performance is not well understood, but a major topic of the evolution of resource allocation and of relevance in human medicine and livestock breeding, for instance. This study aims to show differences of transcript abundance changes during the time intervals before and after two tetanus toxoid (TT) vaccinations in domestic pigs differing in lean growth (LG) and anti-TT-antibody titers (AB) parameters of performance and immunocompetence. During response to the first vaccination all animals had a general decrease in transcript abundances related to various functional pathways as measured by comparative Affymetrix microarray hybridization and Ingenuity Pathway analyses. Low-AB phenotypes had predominantly decreased immune response transcripts. Combined phenotypes high-AB/high-LG had decreased transcripts related to growth factor signaling pathways. However, during the interval after the booster vaccination, high-LG and high-AB animals responded exclusively with increased immune transcripts, such as B-cell receptor signaling and cellular immune response pathways. In addition, high-LG and low-AB animals had predominantly increased transcripts of several cellular immune response pathways. Conversely, low-LG and high-AB animals had few elevated immune transcripts and decreased transcripts related to only two nonimmune-specific pathways. In response to booster vaccination high-LG phenotypes revealed enriched transcripts related to several different immune response pathways, regardless of AB phenotype. Different from the expected impact of AB titers, divergent AB phenotypes did not reflect considerable differences between immune transcripts. However, highly significant differences observed among divergent LG phenotypes suggest the compatibility of high performance and high vaccine responses.

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Use of novel adjuvants and delivery systems to improve the humoral and cellular immune response to malaria vaccine candidate antigens

Vaccine ◽

10.1016/0264-410x(93)90239-t ◽

1993 ◽

Vol 11 (5) ◽

pp. 591-593 ◽

Cited By ~ 16

Author(s):

Daniel M. Gordon

Keyword(s):

Immune Response ◽

Cellular Immune Response ◽

Malaria Vaccine ◽

Vaccine Candidate ◽

Delivery Systems ◽

Malaria Vaccine Candidate ◽

Cellular Immune

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Induction of cellular immune response and anti-Salmonella enterica serovar typhi bactericidal antibodies in healthy volunteers by immunization with a vaccine candidate against typhoid fever

Immunology Letters ◽

10.1016/j.imlet.2004.01.010 ◽

2004 ◽

Vol 93 (2-3) ◽

pp. 115-122 ◽

Cited By ~ 33

Author(s):

Rosa Marı́a Salazar-González ◽

Carmen Maldonado-Bernal ◽

Nora Elena Ramı́rez-Cruz ◽

Nora Rios-Sarabia ◽

Jorge Beltrán-Nava ◽

...

Keyword(s):

Immune Response ◽

Typhoid Fever ◽

Healthy Volunteers ◽

Cellular Immune Response ◽

Salmonella Enterica ◽

Vaccine Candidate ◽

Salmonella Enterica Serovar Typhi ◽

Cellular Immune

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Receptor-binding domain recombinant protein RBD219-N1C1 on alum-CpG induces broad protection against SARS-CoV-2 variants of concern

10.1101/2021.07.06.451353 ◽

2021 ◽

Author(s):

Jeroen Pollet ◽

Ulrich Strych ◽

Wen-Hsiang Chen ◽

Leroy Versteeg ◽

Brian Keegan ◽

...

Keyword(s):

Immune Response ◽

Neutralizing Antibodies ◽

Vaccine Candidate ◽

Neutralizing Antibody ◽

Vaccine Formulation ◽

Broadly Neutralizing Antibodies ◽

Phase 3 ◽

Advanced Phase ◽

Antibody Titers ◽

Cellular Immune

We conducted preclinical studies in mice using a yeast-produced SARS-CoV-2 RBD219-N1C1 subunit vaccine candidate formulated with aluminum hydroxide (alum) and CpG deoxynucleotides. This vaccine formulation is similar to one that entered advanced phase 3 clinical development in India. We compared the immune response of mice vaccinated with RBD219-N1C1/alum to mice vaccinated with RBD219-N1C1/alum+CpG. We also evaluated mice immunized with RBD219-N1C1/alum+CpG and boosted with RBD219-N1C1/alum. Mice were immunized twice intramuscularly at a 21-day interval. Compared to two doses of the RBD219-N1C1/alum formulation, the RBD219-N1C1/alum+CpG vaccine induced a stronger and more balanced Th1/Th2 cellular immune response, with high levels of neutralizing antibodies against the original Wuhan isolate of SARS-CoV-2 as well as the B.1.1.7 (Alpha), B.1.351 (Beta) and B.1.617.1 (Kappa) variants. Notably, the sera from mice that received two 7 μg doses of RBD219-N1C1/alum+CpG showed more than 18 times higher neutralizing antibody titers against B.1.351, than the WHO International Standard for anti-SARS-CoV-2 immunoglobulin NIBSC 20/136. Interestingly, a booster dose did not require the addition of CpG to induce this effect. The data reported here reinforces that the RBD219-N1C1/alum+CpG vaccine formulation is suitable for inducing broadly neutralizing antibodies against SARS-CoV-2 including three variants of concern, B.1.1.7 (Alpha), B.1.351 (Beta), and B.1.617.1 (Kappa).

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Predictors and Dynamics of the Humoral and Cellular Immune Response to SARS-CoV-2 mRNA Vaccines in Hemodialysis Patients: A Multicenter Observational Study

Journal of the American Society of Nephrology ◽

10.1681/asn.2021070908 ◽

2021 ◽

pp. ASN.2021070908

Author(s):

Jens Van Praet ◽

Marijke Reynders ◽

Dirk De Bacquer ◽

Liesbeth Viaene ◽

Melanie Schoutteten ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Healthy Volunteers ◽

Cellular Immune Response ◽

Hemodialysis Patients ◽

Serological Response ◽

Time Points ◽

Vaccine Type ◽

Antibody Titers ◽

Cellular Immune

Background Preliminary evidence suggests that hemodialysis patients have a blunted early serological response to SARS-CoV-2 vaccination. Optimizing vaccination strategy in this population requires a thorough understanding of predictors and dynamics of humoral and cellular immune responses to different SARS-CoV2 vaccines. Methods This prospective multicenter study of 543 hemodialysis patients and 75 healthy volunteers evaluated the immune responses at 4 or 5 weeks and 8 or 9 weeks after administration of the BNT162b2 or mRNA-1273 vaccine, respectively. We assessed anti-SARS-CoV-2 spike antibodies and T cell responses by IFN-γ of peripheral blood lymphocytes upon SARS-CoV-2 glycoprotein stimulation (QuantiFERON assay) and evaluated potential predictors of the responses. Results Compared with healthy volunteers, hemodialysis patients had an incomplete, delayed humoral immune response and a blunted cellular immune response. Geometric mean antibody titers at both time points were significantly greater in patients vaccinated with mRNA-1273 versus BNT162b2, and a larger proportion of them achieved the threshold of 4160 AU/ml, corresponding with high neutralizing antibody titers in vitro (53.6% versus 31.8% at 8 or 9 weeks, P<0.0001). Patients vaccinated with mRNA-1273 versus BNT162b2 exhibited significantly greater median QuantiFERON responses at both time points, and a larger proportion achieved the threshold of 0.15 IU/ml (64.4% versus 46.9% at 8 or 9 weeks, P<0.0001). Multivariate analysis identified COVID-19 experience, vaccine type, use of immunosuppressive drugs, serum albumin, lymphocyte count, hepatitis B vaccine nonresponder status, and dialysis vintage as independent predictors of the humoral and cellular responses. Conclusions The mRNA-1273 vaccine's greater immunogenicity may be related to its higher mRNA dose. This suggests that a high-dose vaccine might improve the impaired immune response to SARS-CoV-2 vaccination in hemodialysis patients.

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