scholarly journals Immunogenicity of Non-Living Anthrax Vaccine Candidates in Cattle and Protective Efficacy of Immune Sera in A/J Mouse Model Compared to the Sterne Live Spore Vaccine

Pathogens ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 557 ◽  
Author(s):  
Solomon Jauro ◽  
Okechukwu C. Ndumnego ◽  
Charlotte Ellis ◽  
Angela Buys ◽  
Wolfgang Beyer ◽  
...  
Keyword(s):  
Immune Response ◽  
Side Effects ◽  
Mouse Model ◽  
Protective Efficacy ◽  
Passive Immunization ◽  
Passive Protection ◽  
Anthrax Vaccine ◽  
Vaccine Candidates ◽  
Veterinary Vaccine ◽  
Polyclonal Igg

The Sterne live spore vaccine (SLSV, Bacillus anthracis strain 34F2) is the veterinary vaccine of choice against anthrax though contra-indicated for use with antimicrobials. However, the use of non-living anthrax vaccine (NLAV) candidates can overcome the SLSV limitation. In this study, cattle were vaccinated with either of the NLAV (purified recombinant PA (PrPA) or crude rPA (CrPA) and formaldehyde-inactivated spores (FIS of B. anthracis strain 34F2) and emulsigen-D®/alhydrogel® adjuvants) or SLSV. The immunogenicity of the NLAV and SLSV was assessed and the protective efficacies evaluated using a passive immunization mouse model. Polyclonal IgG (including the IgG1 subset) and IgM responses increased significantly across all vaccination groups after the first vaccination. Individual IgG subsets titres peaked significantly with all vaccines used after the second vaccination at week 5 and remained significant at week 12 when compared to week 0. The toxin neutralization (TNA) titres of the NLAV vaccinated cattle groups showed similar trends to those observed with the ELISA titres, except that the former were lower, but still significant, when compared to week 0. The opsonophagocytic assay indicated good antibody opsonizing responses with 75% (PrPA+FIS), 66% (CrPA+FIS) and 80% (SLSV) phagocytosis following spores opsonization. In the passive protection test, A/J mice transfused with purified IgG from cattle vaccinated with PrPA+FIS+Emulsigen-D®/Alhydrogel® and SLSV had 73% and 75% protection from challenge with B. anthracis strain 34F2 spores, respectively, whereas IgG from cattle vaccinated with CrPA+FIS+Emulsigen-D®/Alhydrogel® offered insignificant protection of 20%. There was no difference in protective immune response in cattle vaccinated twice with either the PrPA+FIS or SLSV. Moreover, PrPA+FIS did not show any residual side effects in vaccinated cattle. These results suggest that the immunogenicity and protective efficacy induced by the NLAV (PrPA+FIS) in the cattle and passive mouse protection test, respectively, are comparable to that induced by the standard SLSV.

scholarly journals Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

2020 ◽  
Author(s):  
Sarfaraz Ahmad Ejazi ◽  
Smriti Ghosh ◽  
Anirban Bhattacharyya ◽  
Mohd Kamran ◽  
Sonali Das ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Protective Efficacy ◽  
Indian Subcontinent ◽  
Past Infection ◽  
Vaccine Candidates ◽  
Cell Mediated Immune Response ◽  
Membrane Antigens ◽  
Human Use

Abstract Background: Visceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods: In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins. Results: We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions: The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell mediated immune response suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access long-term immune response.

scholarly journals Extended Safety and Efficacy Studies of the Attenuated Brucella Vaccine Candidates 16MΔvjbRand S19ΔvjbRin the Immunocompromised IRF-1−/−Mouse Model

2011 ◽  
Vol 19 (2) ◽  
pp. 249-260 ◽  
Author(s):  
A. M. Arenas-Gamboa ◽  
A. C. Rice-Ficht ◽  
Y. Fan ◽  
M. M. Kahl-McDonagh ◽  
T. A. Ficht
Keyword(s):  
Mouse Model ◽  
Brucella Melitensis ◽  
Protective Efficacy ◽  
Pathological Changes ◽  
Wild Type ◽  
Live Attenuated Vaccine ◽  
Content Type ◽  
Vaccine Candidates ◽  
Multiple Organs ◽  
Efficacious Vaccine

ABSTRACTThe global distribution of brucellosis and high incidence in certain areas of the world warrant the development of a safer and efficacious vaccine. For the past 10 years, we have focused our attention on the development of a safer, but still highly protective, live attenuated vaccine for human and animal use. We have demonstrated the safety and protective efficacy of the vaccine candidates 16MΔvjbRand S19ΔvjbRagainst homologous and heterologous challenge in multiple immunocompetent animal models, including mice and deer. In the present study, we conducted a series of experiments to determine the safety of the vaccine candidates in interferon regulatory factor-1-knockout (IRF-1−/−) mice. IRF-1−/−mice infected with either wild-typeBrucella melitensis16M or the vaccine strainBrucella abortusS19 succumb to the disease within the first 3 weeks of infection, which is characterized by a marked granulomatous and neutrophilic inflammatory response that principally targets the spleen and liver. In contrast, IRF-1−/−mice inoculated with either the 16MΔvjbRor S19ΔvjbRvaccine do not show any clinical or major pathological changes associated with vaccination. Additionally, when 16MΔvjbR- or S19ΔvjbR-vaccinated mice are challenged with wild-typeBrucella melitensis16M, the degree of colonization in multiple organs, along with associated pathological changes, is significantly reduced. These findings not only demonstrate the safety and protective efficacy of thevjbRmutant in an immunocompromised mouse model but also suggest the participation of lesser-known mechanisms in protective immunity against brucellosis.

scholarly journals Nipah Virus: Vaccination and Passive Protection Studies in a Hamster Model

2004 ◽  
Vol 78 (2) ◽  
pp. 834-840 ◽  
Author(s):  
V. Guillaume ◽  
H. Contamin ◽  
P. Loth ◽  
M.-C. Georges-Courbot ◽  
A. Lefeuvre ◽  
...  
Keyword(s):  
Immune Response ◽  
Nipah Virus ◽  
Passive Immunization ◽  
Passive Transfer ◽  
Fruit Bats ◽  
Species Barrier ◽  
Lethal Challenge ◽  
Hamster Model ◽  
Passive Protection ◽  
Challenge Virus

ABSTRACT Nipah virus, a member of the paramyxovirus family, was first isolated and identified in 1999 when the virus crossed the species barrier from fruit bats to pigs and then infected humans, inducing an encephalitis with up to 40% mortality. At present there is no prophylaxis for Nipah virus. We investigated the possibility of vaccination and passive transfer of antibodies as interventions against this disease. We show that both of the Nipah virus glycoproteins (G and F) when expressed as vaccinia virus recombinants induced an immune response in hamsters which protected against a lethal challenge by Nipah virus. Similarly, passive transfer of antibody induced by either of the glycoproteins protected the animals. In both the active and passive immunization studies, however, the challenge virus was capable of hyperimmunizing the vaccinated animals, suggesting that although the virus replicates under these conditions, the immune system can eventually control the infection.

scholarly journals Immunogenicity and Protective Efficacy of a Non-Living Anthrax Vaccine versus a Live Spore Vaccine with Simultaneous Penicillin-G Treatment in Cattle

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 595
Author(s):  
Solomon Jauro ◽  
Okechukwu C. Ndumnego ◽  
Charlotte Ellis ◽  
Angela Buys ◽  
Wolfgang Beyer ◽  
...  
Keyword(s):  
Protective Antigen ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Passive Immunization ◽  
Penicillin G ◽  
Passive Immunisation ◽  
Protective Capacity ◽  
Anthrax Vaccine ◽  
Recombinant Protective Antigen

Sterne live spore vaccine (SLSV) is the current veterinary anthrax vaccine of choice. Unlike the non-living anthrax vaccine (NLAV) prototype, SLSV is incompatible with concurrent antibiotics use in an anthrax outbreak scenario. The NLAV candidates used in this study include a crude recombinant protective antigen (CrPA) and a purified recombinant protective antigen (PrPA) complemented by formalin-inactivated spores and Emulsigen-D®/Alhydrogel® adjuvants. Cattle were vaccinated twice (week 0 and 3) with NLAVs plus penicillin-G (Pen-G) treatment and compared to cattle vaccinated twice with SLSV alone and with Pen-G treatment. The immunogenicity was assessed using ELISA against rPA and FIS, toxin neutralisation assay (TNA) and opsonophagocytic assay. The protection was evaluated using an in vivo passive immunisation mouse model. The anti-rPA IgG titres for NLAVs plus Pen-G and SLSV without Pen-G treatment showed a significant increase, whereas the titres for SLSV plus Pen-G were insignificant compared to pre-vaccination values. A similar trend was measured for IgM, IgG1, and IgG2 and TNA titres (NT50) showed similar trends to anti-rPA titres across all vaccine groups. The anti-FIS IgG and IgM titres increased significantly for all vaccination groups at week 3 and 5 when compared to week 0. The spore opsonising capacity increased significantly in the NLAV vaccinated groups including Pen-G treatment and the SLSV without Pen-G but much less in the SLSV group with Pen-G treatment. Passive immunization of A/J mice challenged with a lethal dose of 34F2 spores indicated significant protective capacity of antibodies raised in the SLSV and the PrPA + FIS + adjuvants vaccinated and Pen-G treated groups but not for the NLAV with the CrPA + FIS + adjuvants and the SLSV vaccinated and Pen-G treated group. Our findings indicate that the PrPA + FIS + Emulsigen-D®/Alhydrogel® vaccine candidate may provide the same level of antibody responses and protective capacity as the SLSV. Advantageously, it can be used concurrently with Penicillin-G in an outbreak situation and as prophylactic treatment in feedlots and valuable breeding stocks.

scholarly journals Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Sarfaraz Ahmad Ejazi ◽  
Smriti Ghosh ◽  
Anirban Bhattacharyya ◽  
Mohd Kamran ◽  
Sonali Das ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Protective Efficacy ◽  
Indian Subcontinent ◽  
Post Treatment ◽  
Vaccine Candidates ◽  
Cell Mediated Immune Response ◽  
Membrane Antigens ◽  
Human Use

Abstract Background Visceral leishmaniasis (VL), is a parasitic disease that causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian subcontinent, the commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, a test of cure in different phases of treatment is still desired. Even though a good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens (LAg), were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six months post-treatment patients. Further, to investigate the immunogenicity of electroeluted proteins, human PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72 and 91 kDa proteins. Results We found that 34 and 51 kDa proteins show 100% sensitivity and specificity with healthy controls and other diseases. After six months post-treatment, antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa proteins are efficient in diagnosis, whereas 72 and 91 kDa proteins may be used to monitor treatment outcome. In another assay, 51 and 63 kDa proteins demonstrated maximum ability to upregulate IFN-γ and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa proteins demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell-mediated immune response, suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access the long-term immune response.

scholarly journals Investigation of the antigenicity and protective efficacy of Leishmania promastigote membrane antigens in search of potential diagnostic and vaccine candidates against visceral leishmaniasis

2020 ◽  
Author(s):  
Sarfaraz Ahmad Ejazi ◽  
Smriti Ghosh ◽  
Anirban Bhattacharyya ◽  
Mohd Kamran ◽  
Sonali Das ◽  
...  
Keyword(s):  
Immune Response ◽  
Visceral Leishmaniasis ◽  
Protective Efficacy ◽  
Indian Subcontinent ◽  
Past Infection ◽  
Vaccine Candidates ◽  
Cell Mediated Immune Response ◽  
Membrane Antigens ◽  
Human Use

Abstract Background Visceral leishmaniasis (VL), a parasitic disease causes serious medical consequences if treatment is delayed. Despite a decline in the number of VL cases in the Indian Subcontinent, commencement of the disease in newer areas continues to be a major concern. Although serological diagnosis mainly by immunochromatographic tests has been found to be effective, test for cure in different phases of treatment is still desired. Even though good prophylactic response has been obtained in murine models by a number of vaccine candidates, few have been proposed for human use. Methods In this study, nine antigenic components (31, 34, 36, 45, 51, 63, 72, 91 and 97 kDa) of Leishmania promastigote membrane antigens, LAg, were electroeluted and evaluated through ELISA to diagnose and distinguish active VL from one month cured and six month past infection. Further, to investigate the immunogenicity of electroeluted proteins, humans PBMCs of cured VL patients were stimulated with 31, 34, 51, 63, 72, and 91 kDa proteins. Results We found that 34 and 51 kDa fractions show 100% sensitivity and specificity with healthy controls and other diseases. After six months post treatment antibodies to 72 and 91 kDa antigens show a significant decline to almost normal levels. This suggests that 34 and 51 kDa are efficient in diagnosis whereas 72 and 91 kDa may be used to monitor treatment outcome. In another study, 51 and 63 kDa proteins demonstrated maximum ability for up-regulate IFN-g and IL-12 with minimum induction of IL-10 and TGF-β. The results indicating that 51 and 63 kDa proteins could be strong candidates for human immunization against VL. In contrast, 34 and 91 kDa demonstrated a reverse profile and may not be a good vaccine candidate. Conclusions The preliminary data obtained in this study proposes the potential of some of the antigens in Leishmania diagnosis and for test of cure. Additionally, some antigens demonstrated good immunoprophylactic cytokine production through T cell mediated immune response suggesting future vaccine candidates for VL. However, further studies are necessary to explore these antigens in diagnosis and to access long-term immune response.

scholarly journals Evaluation of recombinant protein superoxide dismutase of Haemophilus parasuis strain SH0165 as vaccine candidate in a mouse model

2017 ◽  
Vol 63 (4) ◽  
pp. 312-320 ◽  
Author(s):  
Ling Guo ◽  
Lei Xu ◽  
Tao Wu ◽  
Shulin Fu ◽  
Yinsheng Qiu ◽  
...  
Keyword(s):  
Immune Response ◽  
Superoxide Dismutase ◽  
Mouse Model ◽  
Inflammatory Diseases ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Haemophilus Parasuis ◽  
Humoral Immune ◽  
Novel Approach ◽  
Ifn Γ

Haemophilus parasuis can cause a severe membrane inflammation disorder. It has been documented that superoxide dismutase (SOD) is a potential target to treat systemic inflammatory diseases. Therefore, we constructed an experimental H. parasuis subunit vaccine SOD and determined the protective efficacy of SOD using a lethal dose challenge against H. parasuis serovar 4 strain MD0322 and serovar 5 strain SH0165 in a mouse model. The results demonstrated that SOD could induce a strong humoral immune response in mice and provide significant immunoprotection efficacy against a lethal dose of H. parasuis serovar 4 strain MD0322 or serovar 5 strain SH0165 challenge. IgG subtype analysis indicated SOD protein could trigger a bias toward a Th1-type immune response and induce the proliferation of splenocytes and secretion of IL-2 and IFN-γ of splenocytes. In addition, serum in mice from the SOD-immunized group could inhibit the growth of strain MD0322 and strain SH0165 in the whole-blood killing bacteria assay. This is the first report that immunization of mice with SOD protein could provide protective effect against a lethal dose of H. parasuis serovar 4 and serovar 5 challenge in mice, which may provide a novel approach against heterogeneous serovar infection of H. parasuis in future.

scholarly journals Active and Passive Immunizations with Bordetella Colonization Factor A Protect Mice against Respiratory Challenge with Bordetella bronchiseptica

2008 ◽  
Vol 77 (2) ◽  
pp. 885-895 ◽  
Author(s):  
Neelima Sukumar ◽  
Cheraton F. Love ◽  
Matt S. Conover ◽  
Nancy D. Kock ◽  
Purnima Dubey ◽  
...  
Keyword(s):  
Immune Response ◽  
Respiratory Tract ◽  
Protective Efficacy ◽  
Passive Immunization ◽  
Bordetella Bronchiseptica ◽  
Immune Clearance ◽  
Colonization Factor ◽  
Potential Vaccine ◽  
Respiratory Challenge

ABSTRACT Bordetella colonization factor A (BcfA) is an outer membrane immunogenic protein, which is critical for efficient colonization of the murine respiratory tract. These properties of BcfA prompted us to examine its utility in inducing a protective immune response against Bordetella bronchiseptica in a mouse model of intranasal infection. Mice vaccinated with BcfA demonstrated reduced pathology in the lungs and harbored lower bacterial burdens in the respiratory tract. Immunization with BcfA led to the generation of BcfA-specific antibodies in both the sera and lungs, and passive immunization led to the reduction of B. bronchiseptica in the tracheas and lungs. These results suggest that protection after immunization with BcfA is mediated in part by antibodies against BcfA. To further investigate the mechanism of BcfA-induced immune clearance, we examined the role of neutrophils and macrophages. Our results demonstrate that neutrophils are critical for anti-BcfA antibody-mediated clearance and that opsonization with anti-BcfA serum enhances phagocytosis of B. bronchiseptica by murine macrophages. We show that immunization with BcfA results in the production of gamma interferon and subclasses of immunoglobulin G antibodies that are consistent with the induction of a Th1-type immune response. In combination, our findings suggest that the mechanism of BcfA-mediated immunity involves humoral and cellular responses. Expression of BcfA is conserved among multiple clinical isolates of B. bronchiseptica. Our results demonstrate the striking protective efficacy of BcfA-mediated immunization, thereby highlighting its utility as a potential vaccine candidate. These results also provide a model for the development of cell-free vaccines against B. bronchiseptica.

scholarly journals Efficacy of Coxsackievirus A5 Vaccine Candidates in an Actively Immunized Mouse Model

2021 ◽  
Author(s):  
Wei-Ping Jin ◽  
Jia Lu ◽  
Xiao-Yu Zhang ◽  
Jie Wu ◽  
Zhen-Ni Wei ◽  
...  
Keyword(s):  
Animal Model ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Large Scale ◽  
Vaccine Candidate ◽  
Protective Efficacy ◽  
Lethal Dose ◽  
Enterovirus 71 ◽  
Vaccine Candidates ◽  
Enterovirus Serotypes

Coxsackievirus A5 (CV-A5) has recently emerged as a main hand, foot and mouth disease (HFMD) pathogen. Following a large-scale vaccination campaign against enterovirus 71 (EV-71) in China, the number of HFMD-associated cases with EV-71 was reduced, especially severe and fatal cases. However, the total number of HFMD cases remains high, as HFMD is also caused by other enterovirus serotypes. A multivalent HFMD vaccine containing 4 or 6 antigens of enterovirus serotypes is urgently needed. A formaldehyde-inactivated CV-A5 vaccine derived from Vero cells was used to inoculate newborn Kunming mice on days 3 and 10. The mice were challenged on day 14 with a mouse-adapted CV-A5 strain at a lethal dose, which was lethal for 14-day-old suckling mice. Within 14 days post-challenge, groups of mice immunized with three formulations, empty particles (EPs), full particles (FPs) and a mixture of the EP and FP vaccine candidates, all survived, while 100% of the mock-immunized mice died. Neutralizing antibodies (NtAbs) were detected in the sera of immunized mice, and the NtAb levels were correlated with the survival rate of the challenged mice. The virus loads in organs were reduced, and pathological changes and viral protein expression were weak or not observed in the immunized mice compared with those in alum-inoculated control mice. Another interesting finding was the identification of CV-A5 dense particles (DPs), facilitating morphogenesis study. These results demonstrated that the Vero cell-adapted CV-A5 strain is a promising vaccine candidate and could be used as a multivalent HFMD vaccine component in the future. IMPORTANCE The vaccine candidate strain CV-A5 was produced with a high infectivity titer and a high viral particle yield. Three particle forms, empty particles (EPs), full particles (FPs) and dense particles (DPs), were obtained and characterized after purification. The immunogenicities of EP, FP, and EP+FP were evaluated in mice. Mouse-adapted CV-A5 was generated as a challenge strain to infect 14-day-old mice. An active immunization challenge mouse model was established to evaluate the efficacy of the inactivated vaccine candidate. This animal model mimics vaccination, similar immune responses of the vaccinated. The animal model also tests protective efficacy in response to the vaccine against the disease. This work is important for the preparation of multivalent vaccines against HFMD caused by different emerging strains.

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