scholarly journals Overexpression of Interleukin-33 in Recombinant Rabies Virus Enhances Innate and Humoral Immune Responses through Activation of Dendritic Cell-Germinal Center Reactions

Vaccines ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 34
Author(s):  
Zhizhong Mi ◽  
Ling Zhao ◽  
Ming Sun ◽  
Ting Gao ◽  
Yong Wang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Rabies Virus ◽  
Germinal Center ◽  
Neutralizing Antibodies ◽  
Effective Vaccine ◽  
Interleukin 33 ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Long Acting ◽  
High Level

Rabies is a zoonotic infectious disease caused by rabies virus (RABV), and its mortality rate is as high as 100%. Globally, an average of 60,000 people die from rabies each year. The most effective method to prevent and limit rabies is vaccination, but it is currently expensive and inefficient, consisting of a 3-dose series of injections and requiring to be immunized annually. Therefore, it is urgent to develop a single dose of long-acting rabies vaccine. In this study, recombinant rabies virus (rRABV) overexpressing interleukin-33 (IL-33) was constructed and designated as rLBNSE-IL33, and its effect was evaluated in a mouse model. The results showed that rLBNSE-IL33 could enhance the quick production of RABV-induced immune antibodies as early as three days post immunization (dpi) through the activation of dendritic cells (DCs), a component of the innate immune system. Furthermore, rLBNSE-IL33 induced high-level virus-neutralizing antibodies (VNA) production that persisted for 8 weeks by regulating the T cell-dependent germinal center (GC) reaction, thus resulting in better protection against rabies. Our data suggest the IL-33 is a novel adjuvant that could be used to enhance innate and humoral immune responses by activating the DC-GC reaction, and thus, rLBNSE-IL33 could be developed as a safe and effective vaccine for animals.

scholarly journals Recombinant Rabies Virus Overexpressing OX40-Ligand Enhances Humoral Immune Responses by Increasing T Follicular Helper Cells and Germinal Center B Cells

Vaccines ◽  
2020 ◽  
Vol 8 (1) ◽  
pp. 144 ◽  
Author(s):  
Yingying Li ◽  
Ling Zhao ◽  
Baokui Sui ◽  
Zhaochen Luo ◽  
Yachun Zhang ◽  
...  
Keyword(s):  
T Cell ◽  
B Cells ◽  
Immune Responses ◽  
Rabies Virus ◽  
Germinal Center ◽  
Rabies Vaccine ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Follicular Helper ◽  
Ox40 Ligand

Rabies, caused by the rabies virus (RABV), remains a serious threat to public health in most countries. Development of a single-dose and efficacious rabies vaccine is the most important method to restrict rabies virus transmission. Costimulatory factor OX40-ligand (OX40L) plays a crucial role in the T cell-dependent humoral immune responses through T-B cell interaction. In this work, a recombinant RABV overexpressing mouse OX40L (LBNSE-OX40L) was constructed, and its effects on immunogenicity were evaluated in a mouse model. LBNSE-OX40L-immunized mice generated a larger number of T follicular helper (Tfh) cells, germinal center (GC) B cells, and plasma cells (PCs) than the parent virus LBNSE-immunized mice. Furthermore, LBNSE-OX40L induced significantly higher levels of virus-neutralizing antibodies (VNA) as early as seven days post immunization (dpi), which lasted for eight weeks, resulting in better protection for mice than LBNSE (a live-attenuated rabies vaccine strain). Taken together, our data in this study suggest that OX40L can be a novel and potential adjuvant to improve the induction of protective antibody responses post RABV immunization by triggering T cell-dependent humoral immune responses, and that LBNSE-OX40L can be developed as an efficacious and nonpathogenic vaccine for animals.

scholarly journals The vaccinia-based Sementis Copenhagen Vector COVID-19 vaccine induces broad and durable cellular and humoral immune responses

2021 ◽  
Author(s):  
Preethi Eldi ◽  
Tamara H Cooper ◽  
Natalie A Prow ◽  
Liang Liu ◽  
Gary K Heinemann ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
First Generation ◽  
Neutralizing Antibody ◽  
Immune Memory ◽  
Antibody Activity ◽  
Post Vaccination ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Heterologous Boost

The ongoing COVID-19 pandemic perpetuated by SARS-CoV-2 variants, has highlighted the continued need for broadly protective vaccines that elicit robust and durable protection. Here, the vaccinia virus-based, replication-defective Sementis Copenhagen Vector (SCV) was used to develop a first-generation COVID-19 vaccine encoding the spike glycoprotein (SCV-S). Vaccination of mice rapidly induced polyfunctional CD8 T cells with cytotoxic activity and robust Th1-biased, spike-specific neutralizing antibodies, which are significantly increased following a second vaccination, and contained neutralizing activity against the alpha and beta variants of concern. Longitudinal studies indicated neutralizing antibody activity was maintained up to 9 months post-vaccination in both young and aging mice, with durable immune memory evident even in the presence of pre-existing vector immunity. This immunogenicity profile suggests a potential to expand protection generated by current vaccines in a heterologous boost format, and presents a solid basis for second-generation SCV-based COVID-19 vaccine candidates incorporating additional SARS-CoV-2 immunogens.

scholarly journals EFFECT OF BACILLUS OF CALMETTE-GUÉRIN, AVRIDINE AND Propionibacterium acnes AS IMMUNOMODULATORS ON RABIES IN MICE

1999 ◽  
Vol 41 (2) ◽  
pp. 107-114 ◽  
Author(s):  
J. MEGID ◽  
M.T.S. PERAÇOLI ◽  
P.R. CURI ◽  
C.R. ZANETTI ◽  
W.H. CABRERA ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Rabies Virus ◽  
Cellular Immune Response ◽  
Propionibacterium Acnes ◽  
Inoculation Test ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Cellular Immune

The cellular and humoral immune responses of mice inoculated with rabies virus and treated with the Bacillus of Calmette-Guérin, Avridine and Propionibacterium acnes were evaluated in this paper. There was a higher percentage of surviving mice in groups submitted to P. acnes treatment. Lower levels of interferon-<FONT FACE="Symbol">g</font> (IFN-<FONT FACE="Symbol">g</font>) were found in infected mice. The intra-pad inoculation test (IPI) was not effective to detect cellular immune response, contrary to the results found in MIF reaction. The survival of mice did not present correlation with the levels of antirabies serum neutralizing (SN) antibodies titers, IFN-<FONT FACE="Symbol">g</font> concentration and MIF response.

scholarly journals Fast and long-lasting immune response to S-trimer COVID-19 vaccine adjuvanted by PIKA

2021 ◽  
Vol 2 (1) ◽  
Author(s):  
Yuan Liu ◽  
Lianpan Dai ◽  
Xiaoli Feng ◽  
Ran Gao ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Neutralizing Antibody ◽  
Protein Vaccine ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
The Face ◽  
Potential Vaccine ◽  
High Level

AbstractIn the face of the emerging variants of SARS-CoV-2, there is an urgent need to develop a vaccine that can induce fast, effective, long-lasting and broad protective immunity against SARS-CoV-2. Here, we developed a trimeric SARS-CoV-2 S protein vaccine candidate adjuvanted by PIKA, which can induce robust cellular and humoral immune responses. The results showed a high level of neutralizing antibodies induced by the vaccine was maintained for at least 400 days. In the study of non-human primates, PIKA adjuvanted S-trimer induced high SARS-CoV-2 neutralization titers and protected from virus replication in the lung following SARS-CoV-2 challenge. In addition, the long-term neutralizing antibody response induced by S-trimer vaccine adjuvanted by PIKA could neutralize multiple SARS-CoV-2 variants and there is no obvious different among the SARS- CoV-2 variants of interest or concern, including B.1.351, B.1.1.7, P.1, B.1.617.1 and B.1.617.2 variants. These data support the utility of S-trimer protein adjuvanted by PIKA as a potential vaccine candidate against SARS-CoV-2 infection.

scholarly journals Subtle immunological differences in mRNA-1273 and BNT162b2 COVID-19 vaccine induced Fc-functional profiles

2021 ◽  
Author(s):  
Paulina Kaplonek ◽  
Deniz Cizmeci ◽  
Stephanie Fischinger ◽  
Ai-ris Collier ◽  
Todd Suscovich ◽  
...  
Keyword(s):  
Immune Responses ◽  
Specific Antibody ◽  
Neutralizing Antibodies ◽  
Humoral Response ◽  
Hospital Staff ◽  
Differential Protection ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Functional Antibodies ◽  
Functional Profiles

The successful development of several COVID-19 vaccines has substantially reduced morbidity and mortality in regions of the world where the vaccines have been deployed. However, in the wake of the emergence of viral variants, able to evade vaccine induced neutralizing antibodies, real world vaccine efficacy has begun to show differences across the mRNA platforms, suggesting that subtle variation in immune responses induced by the BNT162b2 and mRNA1273 vaccines may provide differential protection. Given our emerging appreciation for the importance of additional antibody functions, beyond neutralization, here we profiled the post-boost binding and functional capacity of the humoral response induced by the BNT162b2 and mRNA-1273 in a cohort of hospital staff. Both vaccines induced robust humoral immune responses to WT SARS-CoV-2 and VOCs. However, differences emerged across epitope-specific responses, with higher RBD- and NTD- specific IgA, as well as functional antibodies (ADNP and ADNK) in mRNA-1273 vaccine recipients. Additionally, RBD-specific antibody depletion highlighted the different roles of non-RBD-specific antibody effector function induced across the mRNA vaccines, providing novel insights into potential differences in protective immunity generated across these vaccines in the setting of newly emerging VOCs.

scholarly journals Overexpression of Interleukin-7 Extends the Humoral Immune Response Induced by Rabies Vaccination

2017 ◽  
Vol 91 (7) ◽  
Author(s):  
Yingying Li ◽  
Ming Zhou ◽  
Zhaochen Luo ◽  
Yachun Zhang ◽  
Min Cui ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Immunological Memory ◽  
Lethal Challenge ◽  
Humoral Immune ◽  
Tfh Cells ◽  
Humoral Immune Responses ◽  
Interleukin 7 ◽  
Rabies Vaccination

ABSTRACT Rabies continues to present a public health threat in most countries of the world. The most efficient way to prevent and control rabies is to implement vaccination programs for domestic animals. However, traditional inactivated vaccines used in animals are costly and have relatively low efficiency, which impedes their extensive use in developing countries. There is, therefore, an urgent need to develop single-dose and long-lasting rabies vaccines. However, little information is available regarding the mechanisms underlying immunological memory, which can broaden humoral responses following rabies vaccination. In this study, a recombinant rabies virus (RABV) that expressed murine interleukin-7 (IL-7), referred to here as rLBNSE-IL-7, was constructed, and its effectiveness was evaluated in a mouse model. rLBNSE-IL-7 induced higher rates of T follicular helper (Tfh) cells and germinal center (GC) B cells from draining lymph nodes (LNs) than the parent virus rLBNSE. Interestingly, rLBNSE-IL-7 improved the percentages of long-lived memory B cells (Bmem) in the draining LNs and plasma cells (PCs) in the bone marrow (BM) for up to 360 days postimmunization (dpi). As a result of the presence of the long-lived PCs, it also generated prolonged virus-neutralizing antibodies (VNAs), resulting in better protection against a lethal challenge than that seen with rLBNSE. Moreover, consistent with the increased numbers of Bmem and PCs after a boost with rLBNSE, rLBNSE-IL-7-immunized mice promptly produced a more potent secondary anti-RABV neutralizing antibody response than rLBNSE-immunized mice. Overall, our data suggest that overexpressing IL-7 improved the induction of long-lasting primary and secondary antibody responses post-RABV immunization. IMPORTANCE Extending humoral immune responses using adjuvants is an important method to develop long-lasting and efficient vaccines against rabies. However, little information is currently available regarding prolonged immunological memory post-RABV vaccination. In this study, a novel rabies vaccine that expressed murine IL-7 was developed. This vaccine enhanced the numbers of Tfh cells and the GC responses, resulting in upregulated quantities of Bmem and PCs. Moreover, we found that the long-lived PCs that were elicited by the IL-7-expressing recombinant virus (rLBNSE-IL-7) were able to sustain VNA levels much longer than those elicited by the parent rLBNSE virus. Upon reexposure to the pathogen, the longevous Bmem, which maintained higher numbers for up to 360 dpi with rLBNSE-IL-7 compared to rLBNSE, could differentiate into antibody-secreting cells, resulting in rapid and potent secondary production of VNAs. These results suggest that the expression of IL-7 is beneficial for induction of potent and long-lasting humoral immune responses.

scholarly journals Monophosphoryl-Lipid A (MPLA) is an Efficacious Adjuvant for Inactivated Rabies Vaccines

Viruses ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1118 ◽  
Author(s):  
Chen Chen ◽  
Chengguang Zhang ◽  
Ruiming Li ◽  
Zongmei Wang ◽  
Yueming Yuan ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Lipid A ◽  
Survival Ratio ◽  
Effective Measure ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Monophosphoryl Lipid A ◽  
Monophosphoryl Lipid

Rabies, as one of the most threatening zoonoses in the world, causes a fatal central nervous system (CNS) disease. So far, vaccination with rabies vaccines has been the most effective measure to prevent and control this disease. At present, inactivated rabies vaccines are widely used in humans and domestic animals. However, humoral immune responses induced by inactivated rabies vaccines are relatively low and multiple shots are required to achieve protective immunity. Supplementation with an adjuvant is a practical way to improve the immunogenicity of inactivated rabies vaccines. In this study, we found that monophosphoryl-lipid A (MPLA), a well-known TLR4 agonist, could significantly promote the maturation of bone marrow-derived dendritic cells (BMDC) through a TLR4-dependent pathway in vitro and the maturation of conventional DCs (cDCs) in vivo. We also found that MPLA, serving as an adjuvant for inactivated rabies vaccines, could significantly facilitate the generation of T follicular helper (Tfh) cells, germinal center (GC) B cells, and plasma cells (PCs), consequently enhancing the production of RABV-specific total-IgG, IgG2a, IgG2b, and the virus-neutralizing antibodies (VNAs). Furthermore, MPLA could increase the survival ratio of mice challenged with virulent RABV. In conclusion, our results demonstrate that MPLA serving as an adjuvant enhances the intensity of humoral immune responses by activating the cDC–Tfh–GC B axis. Our findings will contribute to the improvement of the efficiency of traditional rabies vaccines.

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