A single dose SARS-CoV-2 simulating particle vaccine induces potent neutralizing activities

ABSTRACTCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for which a vaccine is urgently needed to control its spreading. To facilitate the representation of a native-like immunogen without being infectious, here, we reported a SARS-CoV-2 vaccine candidate (designated ShaCoVacc) by incorporating spike-encoding mRNA inside and decorating spike protein on the surface of the virus simulating particles (VSPs) derived from lentiviral particles. We characterized the mRNA copy number, glycosylation status, transduction efficiency, and innate immune property of the new vaccine platform. Importantly, we showed the ShaCoVacc induced strong spike-specific humoral immune responses and potent neutralizing activities by a single injection. Additionally, we disclosed the epitopes of spike-specific antibodies using peptide microarray and revealed epitopes susceptible to specific neutralizing antibodies. These results support further development of ShaCoVacc as a candidate vaccine for COVID-19 and VSP may serve as a new vaccine platform for emerging infectious diseases.

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mRNA vaccination in people over 80 years of age induces strong humoral immune responses against SARS-CoV-2 with cross neutralization of P.1 Brazilian variant

eLife ◽

10.7554/elife.69375 ◽

2021 ◽

Vol 10 ◽

Author(s):

Helen Parry ◽

Gokhan Tut ◽

Rachel Bruton ◽

Sian Faustini ◽

Christine Stephens ◽

...

Keyword(s):

Immune Responses ◽

Cellular Response ◽

Humoral Response ◽

Antibody Responses ◽

Vaccine Platform ◽

Humoral Immune ◽

Vaccine Responses ◽

Cellular Immune Responses ◽

Humoral Immune Responses ◽

Cellular Immune

Age is the major risk factor for mortality after SARS-CoV-2 infection and older people have received priority consideration for COVID-19 vaccination. However, vaccine responses are often suboptimal in this age group and few people over the age of 80 years were included in vaccine registration trials. We determined the serological and cellular response to spike protein in 100 people aged 80–96 years at 2 weeks after the second vaccination with the Pfizer BNT162b2 mRNA vaccine. Antibody responses were seen in every donor with high titers in 98%. Spike-specific cellular immune responses were detectable in only 63% and correlated with humoral response. Previous SARS-CoV-2 infection substantially increased antibody responses after one vaccine and antibody and cellular responses remained 28-fold and 3-fold higher, respectively, after dual vaccination. Post-vaccine sera mediated strong neutralization of live Victoria infection and although neutralization titers were reduced 14-fold against the P.1 variant first discovered in Brazil they remained largely effective. These data demonstrate that the mRNA vaccine platform delivers strong humoral immunity in people up to 96 years of age and retains broad efficacy against the P.1 variant of concern.

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

10.1101/2021.09.06.459206 ◽

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.

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Mathematical modeling and analysis of innate and humoral immune responses to dengue infections

International Journal of Biomathematics ◽

10.1142/s1793524519500773 ◽

2019 ◽

Vol 12 (07) ◽

pp. 1950077 ◽

Cited By ~ 3

Author(s):

Sulanie Perera ◽

S. S. N. Perera

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Steady State ◽

Immune Responses ◽

Dengue Virus ◽

Innate Immune ◽

Virus Dynamics ◽

Quasi Steady State ◽

Humoral Immune ◽

Humoral Immune Responses

Dengue is an acute arthropode-borne virus, belonging to the family Flaviviridae. Currently, there are no vaccines or treatments available against dengue. Thus it is important to understand the dynamics of dengue in order to control the infection. In this paper, we study the long-term dynamics of the model that is presented in [S. D. Perera and S. S. N. Perera, Simulation model for dynamics of dengue with innate and humoral immune responses, Comput. Math. Methods Med. 2018 (2018) 8798057, 18 pp. https://doi.org/10.1155/2018/8798057 ] which describes the interaction of virus with infected and uninfected cells in the presence of innate and humoral immune responses. It was found the model has three equilibria, namely: infection free equilibrium, no immune equilibrium and endemic equilibrium, then analyzed its stability analytically. The analytical findings of each model have been exemplified by numerical simulations. Given the fact that intensity of dengue virus replication at early times of infection could determine clinical outcomes, it is important to understand the impact of innate immunity, which is believed to be the first line of defense against an invading pathogen. For this we carry out a simulation case study to investigate the importance of innate immune response on dengue virus dynamics. A comparison was done assuming that innate immunity was active; innate immunity was in quasi-steady state and innate immunity was inactive during the virus replication process. By a further analysis of the qualitative behavior of the quasi-steady state, it was observed that innate immune response plays a pivotal role in dengue virus dynamics. It can change the dynamical behavior of the system and is essential for the virus clearance.

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Humoral immune responses against the malaria vaccine candidate antigen Plasmodium vivax AMA-1 and IL-4 gene polymorphisms in individuals living in an endemic area of the Brazilian Amazon

Cytokine ◽

10.1016/j.cyto.2015.03.020 ◽

2015 ◽

Vol 74 (2) ◽

pp. 273-278 ◽

Cited By ~ 7

Author(s):

Franciele Maira Moreira Batista Tomaz ◽

Adriana Antônia da Cruz Furini ◽

Marcela Petrolini Capobianco ◽

Marinete Marins Póvoa ◽

Pamella Cristina Alves Trindade ◽

...

Keyword(s):

Immune Responses ◽

Endemic Area ◽

Malaria Vaccine ◽

Vaccine Candidate ◽

Brazilian Amazon ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Vaccine Candidate Antigen ◽

Malaria Vaccine Candidate ◽

Candidate Antigen

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

Molecular Biomedicine ◽

10.1186/s43556-021-00054-z ◽

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.

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

10.1101/2021.08.31.458247 ◽

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.

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

Vaccines ◽

10.3390/vaccines10010034 ◽

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.

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Development of a Multi-Antigenic SARS-CoV-2 Vaccine Using a Synthetic Poxvirus Platform

10.21203/rs.3.rs-40198/v1 ◽

2020 ◽

Author(s):

Flavia Chiuppesi ◽

Marcela d’Alincourt Salazar ◽

Heidi Contreras ◽

Vu Nguyen ◽

Joy Martinez ◽

...

Keyword(s):

Immune Responses ◽

Neutralizing Antibodies ◽

Protective Immunity ◽

Vaccine Candidate ◽

Vaccine Platform ◽

Synthetic Dna ◽

Cellular Immune Responses ◽

Global Pandemic ◽

Immunodominant Antigens ◽

Cellular Immune

Abstract Modified Vaccinia Ankara (MVA) is a highly attenuated poxvirus vector that is widely used to develop vaccines for infectious diseases and cancer. We developed a novel vaccine platform based on a unique three-plasmid system to efficiently generate recombinant MVA vectors from chemically synthesized DNA. In response to the ongoing global pandemic caused by SARS coronavirus-2 (SARS-CoV-2), we used this novel vaccine platform to rapidly produce fully synthetic MVA (sMVA) vectors co-expressing SARS-CoV-2 spike and nucleocapsid antigens, two immunodominant antigens implicated in protective immunity. Mice immunized with these sMVA vectors developed robust SARS-CoV-2 antigen-specific humoral and cellular immune responses, including potent neutralizing antibodies. These results demonstrate the potential of a novel vaccine platform based on synthetic DNA to efficiently generate recombinant MVA vectors and to rapidly develop a multi-antigenic poxvirus-based SARS-CoV-2 vaccine candidate.

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

Journal of Virology ◽

10.1128/jvi.02324-16 ◽

2017 ◽

Vol 91 (7) ◽

Cited By ~ 11

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.

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