A Polysaccharide Purified From Ganoderma lucidum Acts as a Potent Mucosal Adjuvant That Promotes Protective Immunity Against the Lethal Challenge With Enterovirus A71

ABSTRACT The Japanese encephalitis virus (JEV) serocomplex, which also includes Murray Valley encephalitis virus (MVEV), is a group of antigenically closely related, mosquito-borne flaviviruses that are responsible for severe encephalitic disease in humans. While vaccines against the prominent members of this serocomplex are available or under development, it is unlikely that they will be produced specifically against those viruses which cause less-frequent disease, such as MVEV. Here we have evaluated the cross-protective values of an inactivated JEV vaccine (JE-VAX) and a live chimeric JEV vaccine (ChimeriVax-JE) against MVEV in two mouse models of flaviviral encephalitis. We show that (i) a three-dose vaccination schedule with JE-VAX provides cross-protective immunity, albeit only partial in the more severe challenge model; (ii) a single dose of ChimeriVax-JE gives complete protection in both challenge models; (iii) the cross-protective immunity elicited with ChimeriVax-JE is durable (≥5 months) and broad (also giving protection against West Nile virus); (iv) humoral and cellular immunities elicited with ChimeriVax-JE contribute to protection against lethal challenge with MVEV; (v) ChimeriVax-JE remains fully attenuated in immunodeficient mice lacking type I and type II interferon responses; and (vi) immunization with JE-VAX, but not ChimeriVax-JE, can prime heterologous infection enhancement in recipients of vaccination on a low-dose schedule, designed to mimic vaccine failure or waning of vaccine-induced immunity. Our results suggest that the live chimeric JEV vaccine will protect against other viruses belonging to the JEV serocomplex, consistent with the observation of cross-protection following live virus infections.

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Protection from Group B Streptococcal Infection in Neonatal Mice by Maternal Immunization with Recombinant Sip Protein

Infection and Immunity ◽

10.1128/iai.70.9.4897-4901.2002 ◽

2002 ◽

Vol 70 (9) ◽

pp. 4897-4901 ◽

Cited By ~ 42

Author(s):

Denis Martin ◽

Stéphane Rioux ◽

Edith Gagnon ◽

Martine Boyer ◽

Josée Hamel ◽

...

Keyword(s):

Protective Immunity ◽

Group B Streptococcus ◽

Surface Protein ◽

Neonatal Infection ◽

Active Immunization ◽

Infection Model ◽

Lethal Challenge ◽

Specific Antibodies ◽

Pregnant Mice ◽

Group B

ABSTRACT The protective potential of antibodies directed against group B streptococcus (GBS) Sip surface protein was determined by using the mouse neonatal infection model. Rabbit Sip-specific antibodies administered passively to pregnant mice protected their pups against a GBS lethal challenge. In addition, active immunization with purified recombinant Sip protein of female CD-1 mice induced the production of specific antibodies that also confer protection to the newborn pups against GBS strains of serotypes Ia/c, Ib, II, III, and V. These data confirm that Sip-specific antibodies can cross the placenta and conferred protective immunity against GBS infections.

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Inoculation of Balb/c mice with live attenuated tachyzoites protects against a lethal challenge ofNeospora caninum

Parasitology ◽

10.1017/s0031182007003526 ◽

2007 ◽

Vol 135 (1) ◽

pp. 13-21 ◽

Cited By ~ 17

Author(s):

P. M. BARTLEY ◽

S. WRIGHT ◽

F. CHIANINI ◽

D. BUXTON ◽

E. A. INNES

Keyword(s):

Protective Immunity ◽

Neospora Caninum ◽

High Morbidity ◽

Post Challenge ◽

Lethal Challenge ◽

Secondary Challenge ◽

Group 3 ◽

Group 2 ◽

Severe Pathology ◽

Group 1

SUMMARYNeospora caninumtachyzoites attenuated through passage in tissue culture were tested for their ability to induce protective immunity against a lethal challenge dose of parasites. Balb/c mice were each inoculated with either 1×106live virulent tachyzoites (Group 1) or 1×106live attenuated tachyzoites (Group 2), while (Group 3) received a control inoculum. All mice were each challenged 28 days later with 5×106virulent parasites. Histopathological lesions in the brains including necrosis and microgliosis were observed following post-mortem on day 28 post-challenge (p.c.) in 71% of Group 1 and 56% of Group 2. Immunohistochemistry (IHC) of these lesions showed tachyzoites andNeosporaantigens to be associated with moderate brain lesions in 17% of Group 1, while in 11% of Group 2N. caninumtissue cysts were detected, but these were not associated with lesions, Parasite DNA was detected by PCR in the brains of 86% of mice in Group 1 and 56% of mice in Group 2. Following challenge the mice in Group 3 showed high morbidity and 100% mortality within 17 days p.c. Positive IHC forN. caninumwas seen in 88% of the Group 3 mice and parasite DNA was detected in all brain samples. This study shows that it is possible to protect against a lethal challenge ofN. caninumthrough inoculation with attenuated or virulent tachyzoites. However, more severe pathology developed in mice initially inoculated with virulent parasites following a secondary challenge, compared to mice initially inoculated with attenuated parasites.

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Attenuated Nontoxinogenic and Nonencapsulated Recombinant Bacillus anthracis Spore Vaccines Protect against Anthrax

Infection and Immunity ◽

10.1128/iai.68.8.4549-4558.2000 ◽

2000 ◽

Vol 68 (8) ◽

pp. 4549-4558 ◽

Cited By ~ 114

Author(s):

S. Cohen ◽

I. Mendelson ◽

Z. Altboum ◽

D. Kobiler ◽

E. Elhanany ◽

...

Keyword(s):

Bacillus Anthracis ◽

Protective Immunity ◽

Protective Antigen ◽

Cell Vaccine ◽

Lethal Challenge ◽

Electrospray Mass Spectroscopy ◽

Immunological Tests ◽

Anthrax Spores ◽

Biochemical Analyses ◽

Recombinant Protective Antigen

ABSTRACT Several highly attenuated spore-forming nontoxinogenic and nonencapsulated Bacillus anthracis vaccines differing in levels of expression of recombinant protective antigen (rPA) were constructed. Biochemical analyses (including electrospray mass spectroscopy and N terminus amino acid sequencing) as well as biological and immunological tests demonstrated that the rPA retains the characteristics of native PA. A single immunization of guinea pigs with 5 × 107 spores of one of these recombinant strains, MASC-10, expressing high levels of rPA (≥100 μg/ml) from a constitutive heterologous promoter induced high titers of neutralizing anti-PA antibodies. This immune response was long lasting (at least 12 months) and provided protection against a lethal challenge of virulent (Vollum) anthrax spores. The recombinant B. anthracis spore vaccine appears to be more efficacious than the vegetative cell vaccine. Furthermore, while results clearly suggest a direct correlation between the level of expression of PA and the potency of the vaccine, they also suggest that some B. anthracisspore-associated antigen(s) may contribute in a significant manner to protective immunity.

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A Novel High-Intensity Focused Ultrasound-Treated Herpes Simplex Virus 2 Vaccine Induces Long-Term Protective Immunity against Lethal Challenge in Mice

mSphere ◽

10.1128/msphere.00859-20 ◽

2020 ◽

Vol 5 (6) ◽

pp. e00859-20

Author(s):

Juhua Xiao ◽

Xin Zhou ◽

Ye Luo ◽

Shuang Wang ◽

Zhili Yang ◽

...

Keyword(s):

High Intensity ◽

Protective Immunity ◽

Focused Ultrasound ◽

High Intensity Focused Ultrasound ◽

The Novel ◽

Hifu Treatment ◽

Lethal Challenge ◽

Simplex Virus ◽

Herpes Simplex Virus 2

ABSTRACTHigh-intensity focused ultrasound (HIFU), a noninvasive ablation therapy that has been widely used clinically in ablation of solid tumors, induces immune sensitization. We therefore in this study investigated whether HIFU treatment could enhance the efficacy of a herpes simplex virus 2 (HSV-2) vaccine. First, we observed that in HSV-2-positive cervical intraepithelial neoplasia (CIN) II patients, HIFU treatment induced significantly higher anti-HSV-2 neutralization response than surgical removal. Next, we tested the efficacy of HIFU-treated, UV-inactivated HSV-2-infected cells as a proof-of-concept vaccine in mice. Our data showed that HIFU-treated formulation significantly enhanced HSV-2 antibody titers and neutralization titers, compared to UV-, microwave (MW)-, or freeze-thaw (FT)-treated formulations. HIFU treatment also promoted the Th1/2 cell-mediated response. A long-term full protection was observed in mice that received the HIFU-treated formulation, and no weight loss was detected. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.IMPORTANCE High-intensity focused ultrasound (HIFU) is mainly used in tumor ablation and tumor vaccinology study. It has been shown to induce immune sensitization and enhance tumor responsiveness to other therapies. Our study has shown enhanced anti-HSV-2 response in HIFU-treated CIN II patients. Furthermore, in a murine model, we have demonstrated that HIFU-treated HSV-2 vaccine induced long-term protective immunity against lethal challenge. Our findings indicate that the novel application of HIFU in vaccine production may represent a rational way to improve vaccine efficacy.

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Protective immunity to lethal challenge of the 1918 pandemic influenza virus by vaccination

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0607564103 ◽

2006 ◽

Vol 103 (43) ◽

pp. 15987-15991 ◽

Cited By ~ 62

Author(s):

W.-p. Kong ◽

C. Hood ◽

Z.-y. Yang ◽

C.-J. Wei ◽

L. Xu ◽

...

Keyword(s):

Influenza Virus ◽

Pandemic Influenza ◽

Protective Immunity ◽

Lethal Challenge

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A Lactococcus lactis-vectored oral vaccine induces protective immunity of mice against enterotoxigenic Escherichia coli lethal challenge

Immunology Letters ◽

10.1016/j.imlet.2020.06.007 ◽

2020 ◽

Vol 225 ◽

pp. 57-63

Author(s):

Jijun Song ◽

Liangyou Zhao ◽

Mingxin Song

Keyword(s):

Escherichia Coli ◽

Lactococcus Lactis ◽

Protective Immunity ◽

Oral Vaccine ◽

Enterotoxigenic Escherichia Coli ◽

Lethal Challenge

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The High Degree of Sequence Plasticity of the Arenavirus Noncoding Intergenic Region (IGR) Enables the Use of a Nonviral Universal Synthetic IGR To Attenuate Arenaviruses

Journal of Virology ◽

10.1128/jvi.03145-15 ◽

2016 ◽

Vol 90 (6) ◽

pp. 3187-3197 ◽

Cited By ~ 10

Author(s):

Masaharu Iwasaki ◽

Beatrice Cubitt ◽

Brian M. Sullivan ◽

Juan C. de la Torre

Keyword(s):

Public Health ◽

Intergenic Region ◽

Protective Immunity ◽

Hemorrhagic Fever ◽

Health Problems ◽

Wild Type ◽

Lethal Challenge ◽

Important Public Health ◽

High Degree

ABSTRACTHemorrhagic fever arenaviruses (HFAs) pose important public health problems in regions where they are endemic. Concerns about human-pathogenic arenaviruses are exacerbated because of the lack of FDA-licensed arenavirus vaccines and because current antiarenaviral therapy is limited to an off-label use of ribavirin that is only partially effective. We have recently shown that the noncoding intergenic region (IGR) present in each arenavirus genome segment, the S and L segments (S-IGR and L-IGR, respectively), plays important roles in the control of virus protein expression and that this knowledge could be harnessed for the development of live-attenuated vaccine strains to combat HFAs. In this study, we further investigated the sequence plasticity of the arenavirus IGR. We demonstrate that recombinants of the prototypic arenavirus lymphocytic choriomeningitis virus (rLCMVs), whose S-IGRs were replaced by the S-IGR of Lassa virus (LASV) or an entirely nonviral S-IGR-like sequence (Ssyn), are viable, indicating that the function of S-IGR tolerates a high degree of sequence plasticity. In addition, rLCMVs whose L-IGRs were replaced by Ssyn or S-IGRs of the very distantly related reptarenavirus Golden Gate virus (GGV) were viable and severely attenuatedin vivobut able to elicit protective immunity against a lethal challenge with wild-type LCMV. Our findings indicate that replacement of L-IGR by a nonviral Ssyn could serve as a universal molecular determinant of arenavirus attenuation.IMPORTANCEHemorrhagic fever arenaviruses (HFAs) cause high rates of morbidity and mortality and pose important public health problems in regions where they are endemic. Implementation of live-attenuated vaccines (LAVs) will represent a major step to combat HFAs. Here we document that the arenavirus noncoding intergenic region (IGR) has a high degree of plasticity compatible with virus viability. This observation led us to generate recombinant LCMVs containing nonviral synthetic IGRs. These rLCMVs were severely attenuatedin vivobut able to elicit protective immunity against a lethal challenge with wild-type LCMV. These nonviral synthetic IGRs can be used as universal molecular determinants of arenavirus attenuation for the rapid development of safe and effective, as well as stable, LAVs to combat HFA.

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