scholarly journals Non-replicating adenovirus based Mayaro virus vaccine elicits protective immune responses and cross protects against other alphaviruses

2021 ◽  
Vol 15 (4) ◽  
pp. e0009308
Author(s):  
John M. Powers ◽  
Nicole N. Haese ◽  
Michael Denton ◽  
Takeshi Ando ◽  
Craig Kreklywich ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Human Adenovirus ◽  
Viral Disease ◽  
Cross Reactivity ◽  
Immune Serum ◽  
Viral Dissemination ◽  
Lethal Infection ◽  
Mayaro Virus

Mayaro virus (MAYV) is an alphavirus endemic to South and Central America associated with sporadic outbreaks in humans. MAYV infection causes severe joint and muscle pain that can persist for weeks to months. Currently, there are no approved vaccines or therapeutics to prevent MAYV infection or treat the debilitating musculoskeletal inflammatory disease. In the current study, a prophylactic MAYV vaccine expressing the complete viral structural polyprotein was developed based on a non-replicating human adenovirus V (AdV) platform. Vaccination with AdV-MAYV elicited potent neutralizing antibodies that protected WT mice against MAYV challenge by preventing viremia, reducing viral dissemination to tissues and mitigating viral disease. The vaccine also prevented viral-mediated demise in IFN⍺R1-/- mice. Passive transfer of immune serum from vaccinated animals similarly prevented infection and disease in WT mice as well as virus-induced demise of IFN⍺R1-/- mice, indicating that antiviral antibodies are protective. Immunization with AdV-MAYV also generated cross-neutralizing antibodies against two related arthritogenic alphaviruses–chikungunya and Una viruses. These cross-neutralizing antibodies were protective against lethal infection in IFN⍺R1-/- mice following challenge with these heterotypic alphaviruses. These results indicate AdV-MAYV elicits protective immune responses with substantial cross-reactivity and protective efficacy against other arthritogenic alphaviruses. Our findings also highlight the potential for development of a multi-virus targeting vaccine against alphaviruses with endemic and epidemic potential in the Americas.

Tandem antioxidant enzymes confer synergistic protective responses in experimental filariasis

2013 ◽  
Vol 88 (4) ◽  
pp. 402-410 ◽  
Author(s):  
P.R. Prince ◽  
J. Madhumathi ◽  
G. Anugraha ◽  
P.J. Jeyaprita ◽  
M.V.R. Reddy ◽  
...  
Keyword(s):  
Immune Responses ◽  
Redox Regulation ◽  
Protective Efficacy ◽  
Wuchereria Bancrofti ◽  
Parasite Clearance ◽  
Cross Reactivity ◽  
Host Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Helminth Parasites ◽  
Cellular Immune

AbstractHelminth parasites use antioxidant defence strategies for survival during oxidative stress due to free radicals in the host. Accordingly, tissue-dwelling filarial parasites counteract host responses by releasing a number of antioxidants. Targeting these redox regulation proteins together, would facilitate effective parasite clearance. Here, we report the combined effect of protective immune responses trigged by recombinant Wuchereria bancrofti thioredoxin (WbTRX) and thioredoxin peroxidase (WbTPX) in an experimental filarial model. The expression of WbTRX and WbTPX in different stages of the parasite and their cross-reactivity were analysed by enzyme-linked immunosorbent assay (ELISA). The immunogenicity of recombinant proteins and their protective efficacy were studied in animal models when immunized in single or cocktail mode. The antigens showed cross-reactive epitopes and induced high humoral and cellular immune responses in mice. Further, parasite challenge against Brugia malayi L3 larvae in Mastomyscoucha conferred significant protection of 57% and 62% against WbTRX and WbTPX respectively. The efficacy of L3 clearance was significantly higher (71%) (P <  0.001) when the antigens were immunized together, showing a synergistic effect in multiple-mode vaccination. Hence, the study suggests WbTRX and WbTPX to be attractive vaccine candidates when immunized together and provides a tandem block for parasite elimination in the control of lymphatic filariasis.

scholarly journals Transcutaneous Immunization with a Vibrio cholerae O1 Ogawa Synthetic Hexasaccharide Conjugate following Oral Whole-Cell Cholera Vaccination Boosts Vibriocidal Responses and Induces Protective Immunity in Mice

2012 ◽  
Vol 19 (4) ◽  
pp. 594-602 ◽  
Author(s):  
A. A. Tarique ◽  
A. Kalsy ◽  
M. Arifuzzaman ◽  
S. M. Rollins ◽  
R. C. Charles ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vibrio Cholerae ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Immune Serum ◽  
Whole Cell ◽  
Content Type ◽  
Specific Polysaccharide ◽  
Subcutaneous Immunization ◽  
Cholera Vaccination

ABSTRACTA shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide ofVibrio choleraeO1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) orEscherichia coliheat-labile toxin (LT) following oral priming with attenuatedV. choleraeO1 vaccine strain O395-NT resulted in significant increases in serum anti-V. choleraeLPS IgG, IgM, and IgA (P< 0.01) responses as well as in anti-Ogawa (P< 0.01) and anti-Inaba (P< 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P< 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses againstV. cholerae.

scholarly journals Induction of Immune Responses in Mice and Monkeys to Ebola Virus after Immunization with Liposome-Encapsulated Irradiated Ebola Virus: Protection in Mice Requires CD4+ T Cells

2002 ◽  
Vol 76 (18) ◽  
pp. 9176-9185 ◽  
Author(s):  
Mangala Rao ◽  
Mike Bray ◽  
Carl R. Alving ◽  
Peter Jahrling ◽  
Gary R. Matyas
Keyword(s):  
T Lymphocytes ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Ebola Virus ◽  
Protective Efficacy ◽  
Hemorrhagic Fever ◽  
Surface Glycoprotein ◽  
Antibody Treatment ◽  
Amino Terminal ◽  
Monoclonal Antibody Treatment

ABSTRACT Ebola Zaire virus (EBO-Z) causes severe hemorrhagic fever in humans, with a high mortality rate. It is thought that a vaccine against EBO-Z may have to induce both humoral and cell-mediated immune responses to successfully confer protection. Because it is known that liposome-encapsulated antigens induce both antibody and cellular responses, we evaluated the protective efficacy of liposome-encapsulated irradiated EBO-Z [L(EV)], which contains all of the native EBO-Z proteins. In a series of experiments, mice immunized intravenously with L(EV) were completely protected (94/94 mice) against illness and death when they were challenged with a uniformly lethal mouse-adapted variant of EBO-Z. In contrast, only 55% of mice immunized intravenously with nonencapsulated irradiated virus (EV) survived challenge, and all became ill. Treatment with anti-CD4 antibodies before or during immunization with L(EV) eliminated protection, while treatment with anti-CD8 antibodies had no effect, thus indicating a requirement for CD4+ T lymphocytes for successful immunization. On the other hand, treatment with either anti-CD4 or anti-CD8 antibodies after immunization did not abolish the protection. After immunization with L(EV), antigen-specific gamma interferon (IFNγ)-secreting CD4+ T lymphocytes were induced as analyzed by enzyme-linked immunospot assay. Anti-CD4 monoclonal antibody treatment abolished IFNγ production (80 to 90% inhibition compared to that for untreated mice). Mice immunized with L(EV), but not EV, developed cytotoxic T lymphocytes specific to two peptides (amino acids [aa] 161 to 169 and aa 231 to 239) present in the amino-terminal end of the EBO-Z surface glycoprotein. Because of the highly successful results in the mouse model, L(EV) was also tested in three cynomolgus monkeys. Although immunization of the monkeys with L(EV)-induced virus-neutralizing antibodies against EBO-Z caused a slight delay in the onset of illness, it did not prevent death.

scholarly journals Immunogenicity and Protective Efficacy of DNA Vaccines Expressing Rhesus Cytomegalovirus Glycoprotein B, Phosphoprotein 65-2, and Viral Interleukin-10 in Rhesus Macaques

2006 ◽  
Vol 81 (3) ◽  
pp. 1095-1109 ◽  
Author(s):  
Yujuan Yue ◽  
Amitinder Kaur ◽  
Meghan K. Eberhardt ◽  
Nadine Kassis ◽  
Shan Shan Zhou ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Dna Vaccines ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Interleukin 10 ◽  
Antibody Responses ◽  
Glycoprotein B ◽  
Viral Loads ◽  
Rhesus Cytomegalovirus

ABSTRACT Rhesus cytomegalovirus (RhCMV) infection of macaques exhibits strong similarities to human CMV (HCMV) persistence and pathogenesis. The immunogenicity of DNA vaccines encoding three RhCMV proteins (a truncated version of glycoprotein B lacking the transmembrane region and endodomain [gBΔTM], phosphoprotein 65-2 [pp65-2], and viral interleukin-10 [vIL-10]) was evaluated in rhesus macaques. Two groups of monkeys (four per group) were genetically immunized four times with a mixture of either pp65-2 and gBΔTM or pp65-2, vIL-10, and gBΔTM. The vaccinees developed anti-gB and anti-pp65-2 antibodies in addition to pp65-2 cellular responses after the second booster immunization, with rapid responses observed with subsequent DNA injections. Weak vIL-10 immune responses were detected in two of the four immunized animals. Neutralizing antibodies were detected in seven monkeys, although titers were weak compared to those observed in naturally infected animals. The immunized monkeys and naïve controls were challenged intravenously with 105 PFU of RhCMV. Anamnestic binding and neutralizing antibody responses were observed 1 week postchallenge in the vaccinees. DNA vaccination-induced immune responses significantly decreased peak viral loads in the immunized animals compared to those in the controls. No difference in peak viral loads was observed between the pp65-2/gBΔTM DNA- and pp65-2/vIL-10/gBΔTM-vaccinated groups. Antibody responses to nonvaccine antigens were lower postchallenge in both vaccine groups than in the controls, suggesting long-term control of RhCMV protein expression. These data demonstrated that DNA vaccines targeting the RhCMV homologues of HCMV gB and pp65 altered the course of acute and persistent RhCMV infection in a primate host.

scholarly journals Kinetics of Immune Responses to Influenza Virus-Like Particles and Dose-Dependence of Protection with a Single Vaccination

2009 ◽  
Vol 83 (9) ◽  
pp. 4489-4497 ◽  
Author(s):  
Fu Shi Quan ◽  
Dae-Goon Yoo ◽  
Jae-Min Song ◽  
John D. Clements ◽  
Richard W. Compans ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Time Course ◽  
Protective Efficacy ◽  
Dependent Manner ◽  
Lethal Challenge ◽  
Promising Alternative ◽  
Virus Like Particles ◽  
Kinetics Of

ABSTRACT The format of influenza virus-like particles (VLPs) as a nonreplicating particulate vaccine candidate is a promising alternative to conventional egg-based vaccines. In this study, we have investigated the detailed kinetics of immune responses and protective efficacy after a single intranasal immunization with different doses of VLPs alone or in the presence of an Escherichia coli mutant heat-labile enterotoxin [mLT(R192G)] or cholera toxin subunit B as adjuvants. Analysis of immune responses showed differential kinetics in a VLP antigen dose-dependent manner and dynamic changes in the ratios of antibody immunoglobulin G isotypes over the time course. Protection against lethal challenge was observed with a single immunization with influenza VLPs even without adjuvant. The addition of adjuvant showed significant antigen-sparing effects with improved protective efficacy. The protective immune responses, efficacies of protection, and antigen-sparing effects were significantly improved by a second immunization as determined by the levels of neutralizing antibodies, morbidity postchallenge, lung viral titers, and inflammatory cytokines. Our results are informative for a better understanding of the protective immunity induced by a single dose or two doses of influenza VLPs, which is dependent on antigen dosage and the presence of adjuvant, and will provide insights into designing effective vaccines based on VLPs.

scholarly journals Antibody Breadth and Protective Efficacy Are Increased by Vaccination with Computationally Optimized Hemagglutinin but Not with Polyvalent Hemagglutinin-Based H5N1 Virus-Like Particle Vaccines

2011 ◽  
Vol 19 (2) ◽  
pp. 128-139 ◽  
Author(s):  
Brendan M. Giles ◽  
Stephanie J. Bissel ◽  
Dilhari R. DeAlmeida ◽  
Clayton A. Wiley ◽  
Ted M. Ross
Keyword(s):  
Immune Responses ◽  
Antibody Response ◽  
Viral Replication ◽  
Protective Efficacy ◽  
Cellular Responses ◽  
Immune Serum ◽  
Influenza Viruses ◽  
H5n1 Influenza ◽  
Virus Like Particle ◽  
Virus Recovery

ABSTRACTOne of the challenges for developing an H5N1 influenza vaccine is the diversity of antigenically distinct isolates within this subtype. Previously, our group described a novel hemagglutinin (HA) derived from a methodology termed computationally optimized broadly reactive antigen (COBRA). This COBRA HA, when used as an immunogen, elicits a broad antibody response against H5N1 isolates from different clades. In this report, the immune responses elicited by the COBRA HA virus-like particle (VLP) vaccine were compared to responses elicited by a mixture of VLPs expressing representative HA molecules from clade 2.1, 2.2, and 2.3 primary H5N1 isolates (polyvalent). The COBRA HA VLP vaccine elicited higher-titer antibodies to a panel of H5N1 HA proteins than did the other VLPs. Both COBRA and polyvalent vaccines protected vaccinated mice and ferrets from experimental infection with highly lethal H5N1 influenza viruses, but COBRA-vaccinated animals had decreased viral replication, less inflammation in the lungs of mice, and reduced virus recovery in ferret nasal washes. Both vaccines had similar cellular responses postchallenge, indicating that higher-titer serum antibodies likely restrict the duration of viral replication. Furthermore, passively transferred immune serum from the COBRA HA VLP-vaccinated mice protected recipient animals more efficiently than immune serum from polyvalent-vaccinated mice. This is the first report comparing these two vaccine strategies. The single COBRA HA antigen elicited a broader antibody response and reduced morbidity and viral titers more effectively than a polyvalent mixture of primary H5N1 HA antigens.

Cross-reactivity reduced dengue virus 2 vaccine has no cross-protection against heterotypic dengue viruses

2020 ◽  
Vol 15 (2) ◽  
pp. 79-90
Author(s):  
Jedhan U Galula ◽  
Chung-Yu Yang ◽  
Brent S Davis ◽  
Gwong-Jen J Chang ◽  
Day-Yu Chao
Keyword(s):  
Survival Rate ◽  
Dengue Virus ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Protective Efficacy ◽  
Cross Reactivity ◽  
Lethal Challenge ◽  
Denv Serotypes ◽  
Female Mice ◽  
Virus Like Particle

Aim: This study assessed how prime-boost strategies influence the immunogenicity of a cross-reactivity reduced dengue virus 2 vaccine (DENV-2 RD). Materials & methods: Mice were immunized with DENV-2 RD vaccines in a heterologous DNA and virus-like particle (VLP) prime-boost. Elicited antibodies were analyzed for neutralization and protective efficacy against four DENV serotypes. Results: DENV-2 RD DNA-VLP had induced higher and broader levels of total IgG and neutralizing antibodies with statistically significant IgG titers against DENV-2 and -3. Only pups of DENV-2 RD DNA-VLP immunized female mice were fully protected against homotypic DENV challenge and partially protected (60% survival rate) against heterotypic DENV-3 lethal challenge. Conclusion: DENV-2 RD vaccine requires a multivalent format to effectively elicit a balanced and protective immunity across all four DENV serotypes.

scholarly journals Comparative Evaluation of the Vaccine Efficacies of Three Adenovirus-Based Vector Types in the Friend Retrovirus Infection Model

2019 ◽  
Vol 93 (21) ◽  
Author(s):  
Camilla Patrizia Hrycak ◽  
Sonja Windmann ◽  
Wibke Bayer
Keyword(s):  
T Cells ◽  
Immune Responses ◽  
Neutralizing Antibodies ◽  
Cross Reactivity ◽  
Infection Model ◽  
Friend Retrovirus ◽  
Wide Range ◽  
The Individual ◽  
High Level ◽  
Cellular Immune

ABSTRACT Adenovirus (AdV)-based vectors are popular experimental vaccine vectors, but despite their ability to induce strong immune responses, their application is impeded by widespread preexisting immunity against many AdV types that can impair or even abrogate the induction of transgene-specific immune responses. Therefore, the development of vectors based on AdV types with a low seroprevalence is important for effective AdV-based immunization in humans. We investigated the immunization efficacy of vectors based on AdV type 48 (Ad48) and Ad50 in the ovalbumin (ova) model as well as the Friend retrovirus (FV) model, which allows testing of the protective effect of vaccine-induced immunity. Using ova-encoding vectors, we found a significantly lower induction of ova-specific CD8+ T cells and antibody responses by Ad48- and Ad50-based vectors than by Ad5-based vectors. Similarly, we found a reduced induction of FV-specific CD8+ T cell responses in Ad48- and Ad50.Leader-Gag-immunized mice compared with that in Ad5-immunized mice; however, some of those mice were able to control the FV infection, and protection correlated with the level of neutralizing antibodies 10 days after FV challenge. Analyses of the AdV-specific antibodies and CD8+ T cells induced by the individual AdV types revealed a high level of cross-reactivity, and the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Our results show that the immunity induced by Ad48- and Ad50-based vectors is reduced compared to that induced by Ad5 and is sufficient to control FV infection in only some of the immunized mice. A high level of cross-reactivity suggests that AdV preimmunity must be considered even when applying rare AdV-based vectors. IMPORTANCE AdV-based vectors are important tools for the development of vaccines against a wide range of pathogens. While AdV vectors are generally considered safe and highly effective, their application can be severely impaired by preexisting immunity due to the widespread seroprevalence of some AdV types. The characterization of different AdV types with regard to immunogenicity and efficacy in challenge models is of great importance for the development of improved AdV-based vectors that allow for efficient immunization despite anti-AdV immunity. We show that the immunity induced by an Ad48-based vector is inferior to that induced by an Ad5-based vector but can still mediate the control of an FV infection in highly FV-susceptible mice. However, the efficacy of Ad48-based immunization was impaired in Ad5-preimmune mice. Importantly, we found cross-reactivity of both the humoral and cellular immune responses raised by the individual AdV types, suggesting that switching to a different AdV type may not be sufficient to circumvent preexisting anti-AdV immunity.

scholarly journals Production of equine sera as a potential immunotherapy against COVID-19

2021 ◽  
Vol 62 ◽  
pp. 3-17
Author(s):  
Mariana V Cepeda ◽  
Juan C. Jiménez ◽  
Flor H. Pujol ◽  
Héctor R. Rangel ◽  
Carlos Bello ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Passive Immunization ◽  
Viral Disease ◽  
High Titre ◽  
Immune Serum ◽  
Receptor Binding Domain ◽  
Emerging Viruses ◽  
Protein Receptor ◽  
Equine Plasma ◽  
Elisa Titre

Emerging viruses such as the COVID-19-inducing virus, SARSCoV- 2, represent a threat to human health, unless effective vaccines, drugs or alternative treatments, such as passive immunization, become accessible. Animal-derived immunoglobulins, such as equine immunoglobulins might be useful as immunoprophylaxis or immunotherapy against this viral disease. Therapeutic antibodies (Abs) for SARS-CoV-2 were obtained from hyperimmune equine plasma using the Spike protein receptor binding domain (RBD) as an immunogen. The presence of anti-RBD antibodies was evaluated by ELISA and the titres of neutralizing antibodies were determined in viral cell culture. Immunized horses generated high-titre of anti-RBD antibodies with antiviral neutralizing activity on Vero-E6 cells of 1/1,000. To minimize potential adverse effects, the immunoglobulins were digested with pepsin, and purified to obtain the F(ab’)2 fragments with the protocol standardized by Biotecfar C.A for the production of snake antivenom. Pre-immune serum displayed an unexpected anti-RBD reactivity by ELISA (titre up to 1/900) and Western Blot, but no angioneutralizing activity. Modelling of the RBD of equine coronavirus showed that some of the known epitopes of SARS-CoV-2 RBD were structurally conserved in the equine coronavirus protein. This might suggest that some of the reactivity observed in the pre-immune serum to the SARS-CoV-2 RBD might be due to a previous exposure to equine coronavirus.

scholarly journals Breadth of humoral immune responses to the C-terminus of the circumsporozoite protein is associated with protective efficacy induced by the RTS,S malaria vaccine

2020 ◽  
Author(s):  
Sidhartha Chaudhury ◽  
Randall S. MacGill ◽  
Angela M. Early ◽  
Jessica S. Bolton ◽  
C. Richter King ◽  
...  
Keyword(s):  
Immune Responses ◽  
Malaria Vaccine ◽  
Protective Efficacy ◽  
Cross Reactivity ◽  
Antibody Responses ◽  
Circumsporozoite Protein ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
C Terminus ◽  
Fold Reduction

AbstractThe circumsporozoite protein (CSP) is the main surface antigen of malaria sporozoites and a prime vaccine target. Responses induced by the CSP-based RTS,S vaccine towards the polymorphic C-terminal region of P.falciparum-CSP raise concerns that vaccines using single alleles may have lower efficacy against genotypic variants. We characterized the extent of C-terminal cross-reactivity of antibodies induced by RTS,S (based on the 3D7 allele) with variants representing seven circulating field isolates through a novel HTS-multiplex assay for screening closely related peptides. Reactivity to variants showed approximately 30-fold reduction in recognition relative to 3D7. The degree of reduced cross-reactivity,ranging from 21 to 69-fold, directly correlated with the number of polymorphisms between variants and 3D7. Surprisingly, protection assessed by challenge with 3D7 parasites was strongly associated with higher C-terminal antibody breadth suggesting that C-terminal specific avidity or fine-specificity may play a role in RTS,S/AS01B-mediated protection and that breadth of C-terminal CSP-specific antibody responses may be a marker of protection.

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