Name: Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice (Video) | JoVE Journal
Uploaded: 2019-02-22T13:30:00.000+00:00
Duration: 8 min 52 s
Description: Learn to evaluate host-pathogen responses and vaccine efficacy in mice using in vivo immunization and bacterial challenge techniques. This protocol enables assessment of immune responses and bacterial burden in respiratory tissues.

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5 minutes

This work was supported by 1R01AI125560-01 and start-up funds from The Ohio State University.

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<li>Marr, N., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Protective+activity+of+the+Bordetella+pertussis+BrkA+autotransporter+in+the+murine+lung+colonization+model%5BTitle%5D)+AND+%22Vaccine%22%5BJournal%5D)">Protective activity of the Bordetella pertussis BrkA autotransporter in the murine lung colonization model.</a> Vaccine. 26 (34), 4306-4311 (2008).</li>
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<li>Zhang, L., Wang, W., Wang, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Effect+of+vaccine+administration+modality+on+immunogenicity+and+efficacy%5BTitle%5D)+AND+%22Expert+Review+of+Vaccines%22%5BJournal%5D)">Effect of vaccine administration modality on immunogenicity and efficacy.</a> Expert Review of Vaccines. 14 (11), 1509-1523 (2015).</li>
<li>Ross, P. J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Relative+Contribution+of+Th1+and+Th17+Cells+in+Adaptive+Immunity+to+Bordetella+pertussis%3A+Towards+the+Rational+Design+of+an+Improved+Acellular+Pertussis+Vaccine%5BTitle%5D)+AND+%22PLoS+Pathogens%22%5BJournal%5D)">Relative Contribution of Th1 and Th17 Cells in Adaptive Immunity to Bordetella pertussis: Towards the Rational Design of an Improved Acellular Pertussis Vaccine.</a> PLoS Pathogens. 9 (4), 1003264(2013).</li>
<li>Warfel, J. M., Zimmerman, L. I., Merkel, T. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Acellular+pertussis+vaccines+protect+against+disease+but+fail+to+prevent+infection+and+transmission+in+a+nonhuman+primate+model%5BTitle%5D)+AND+%22Proceedings+of+the+National+Academy+of+Sciences+USA%22%5BJournal%5D)">Acellular pertussis vaccines protect against disease but fail to prevent infection and transmission in a nonhuman primate model.</a> Proceedings of the National Academy of Sciences USA. 111 (2), 787-792 (2014).</li>
<li>Allen, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Sustained+protective+immunity+against+Bordetella+pertussis+nasal+colonization+by+intranasal+immunization+with+a+vaccine-adjuvant+combination+that+induces+IL-17-secreting+TRM+cells%5BTitle%5D)+AND+%22Mucosal+Immunology%22%5BJournal%5D)">Sustained protective immunity against Bordetella pertussis nasal colonization by intranasal immunization with a vaccine-adjuvant combination that induces IL-17-secreting TRM cells.</a> Mucosal Immunology. , (2018).</li>
<li>Solans, L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((IL-17-dependent+SIgA-mediated+protection+against+nasal+Bordetella+pertussis+infection+by+live+attenuated+BPZE1+vaccine%5BTitle%5D)+AND+%22Mucosal+Immunology%22%5BJournal%5D)">IL-17-dependent SIgA-mediated protection against nasal Bordetella pertussis infection by live attenuated BPZE1 vaccine.</a> Mucosal Immunology. , (2018).</li>
<li>Miller, M. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Visualization+of+murine+intranasal+dosing+efficiency+using+luminescent+Francisella+tularensis%3A+effect+of+instillation+volume+and+form+of+anesthesia%5BTitle%5D)+AND+%22PLoS+One%22%5BJournal%5D)">Visualization of murine intranasal dosing efficiency using luminescent Francisella tularensis: effect of instillation volume and form of anesthesia.</a> PLoS One. 7 (2), 31359(2012).</li>
<li>Sato, Y., Izumiya, K., Sato, H., Cowell, J. L., Manclark, C. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Aerosol+infection+of+mice+with+Bordetella+pertussis%5BTitle%5D)+AND+%22Infection+and+Immunity%22%5BJournal%5D)">Aerosol infection of mice with Bordetella pertussis.</a> Infection and Immunity. 29 (1), 261-266 (1980).</li>
<li>Warfel, J. M., Beren, J., Merkel, T. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Airborne+transmission+of+Bordetella+pertussis%5BTitle%5D)+AND+%22Journal+of+Infectious+Diseases%22%5BJournal%5D)">Airborne transmission of Bordetella pertussis.</a> Journal of Infectious Diseases. 206 (6), 902-906 (2012).</li>
<li>Scanlon, K. M., Snyder, Y. G., Skerry, C., Carbonetti, N. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Fatal+Pertussis+in+the+Neonatal+Mouse+Model+Is+Associated+with+Pertussis+Toxin-Mediated+Pathology+beyond+the+Airways%5BTitle%5D)+AND+%22Infection+and+Immunity%22%5BJournal%5D)">Fatal Pertussis in the Neonatal Mouse Model Is Associated with Pertussis Toxin-Mediated Pathology beyond the Airways.</a> Infection and Immunity. 85 (11), (2017).</li>
<li>Martinez de Tejada, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Neither+the+Bvg-+phase+nor+the+vrg6+locus+of+Bordetella+pertussis+is+required+for+respiratory+infection+in+mice%5BTitle%5D)+AND+%22Infection+and+Immunity%22%5BJournal%5D)">Neither the Bvg- phase nor the vrg6 locus of Bordetella pertussis is required for respiratory infection in mice.</a> Infection and Immunity. 66 (6), 2762-2768 (1998).</li>
<li>Higgins, S. C., Jarnicki, A. G., Lavelle, E. C., Mills, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((TLR4+mediates+vaccine-induced+protective+cellular+immunity+to+Bordetella+pertussis%3A+role+of+IL-17-producing+T-cells%5BTitle%5D)+AND+%22Journal+of+Immunology%22%5BJournal%5D)">TLR4 mediates vaccine-induced protective cellular immunity to Bordetella pertussis: role of IL-17-producing T-cells.</a> Journal of Immunology. 177 (11), 7980-7989 (2006).</li>
<li>Mahon, B. P., Brady, M. T., Mills, K. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Protection+against+Bordetella+pertussis+in+mice+in+the+absence+of+detectable+circulating+antibody%3A+implications+for+long-term+immunity+in+children%5BTitle%5D)+AND+%22Journal+of+Infectious+Diseases%22%5BJournal%5D)">Protection against Bordetella pertussis in mice in the absence of detectable circulating antibody: implications for long-term immunity in children.</a> Journal of Infectious Diseases. 181 (6), 2087-2091 (2000).</li>
<li>Karlsson, A. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Comparison+of+the+ELISPOT+and+cytokine+flow+cytometry+assays+for+the+enumeration+of+antigen-specific+T-cells%5BTitle%5D)+AND+%22Journal+of+Immunological+Methods%22%5BJournal%5D)">Comparison of the ELISPOT and cytokine flow cytometry assays for the enumeration of antigen-specific T-cells.</a> Journal of Immunological Methods. 283 (1-2), 141-153 (2003).</li>
<li>Hagen, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Comparative+Multi-Donor+Study+of+IFNgamma+Secretion+and+Expression+by+Human+PBMCs+Using+ELISPOT+Side-by-Side+with+ELISA+and+Flow+Cytometry+Assays%5BTitle%5D)+AND+%22Cells%22%5BJournal%5D)">Comparative Multi-Donor Study of IFNgamma Secretion and Expression by Human PBMCs Using ELISPOT Side-by-Side with ELISA and Flow Cytometry Assays.</a> Cells. 4 (1), 84-95 (2015).</li>
<li>Raeven, R. H. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/pubmed?term=((Molecular+and+cellular+signatures+underlying+superior+immunity+against+Bordetella+pertussis+upon+pulmonary+vaccination%5BTitle%5D)+AND+%22Mucosal+Immunology%22%5BJournal%5D)">Molecular and cellular signatures underlying superior immunity against Bordetella pertussis upon pulmonary vaccination.</a> Mucosal Immunology. 11 (3), 1009(2018).</li>
</ol>

The authors have nothing to disclose.

The comprehensive protocol described here to study vaccine-induced immunity to B. pertussis infection will also permit evaluation of host responses to a variety of other pathogens. The protocol discusses methods to deliver immunizations, determine vaccine efficacy following pathogen challenge, and parallel dissection of immune function. In adapting the protocol in order to study other pathogens, several parameters would need to be modified. These include, but are not limited to, the mode of animal anesthesia, va...

Vaccines represent one of the greatest public health achievements of the 20th century, yet we still do not fully understand the mechanisms by which successful vaccines stimulate protective immunity. The identification of molecular signatures (e.g., cell activation markers, expansion of cellular subtypes, and patterns of gene expression) induced after vaccination provides a plethora of information for predicting and generating an efficacious immune response. The complexity of host-pathogen responses cannot be adequately replicated using in vitro cell culture systems1. In vivo vaccine models are designed to concomitantly evaluate multiple immune cell types within the host. This provides an advantage when characterizing vaccine antigen processing and presentation, differential cytokine secretion, and expansion of immune cells. The protocol described here provides a detailed method to determine vaccine efficacy through evaluation of the systemic and local immune responses and quantification of pathogen burden in tissues of interest. The example provided here tests the efficacy of an experimental vaccine for the pathogen Bordetella pertussis (B. pertussis).
B. pertussis is a gram-negative bacterium that is the etiological agent of the respiratory disease whooping cough (pertussis)2,3. Close contact with infected individuals (symptomatic or asymptomatic) leads to transmission, colonization, and disease. Despite significant global vaccine coverage4, pertussis is considered a resurging disease in many nations around the world and is a major cause of preventable childhood deaths5,6,7,8. In 2015, B. pertussis and pertussis were included in the National Institute of Allergy and infectious Diseases (NIAID) emerging infectious pathogen/disease list, emphasizing the need for development of a better vaccine that confers long-lived protective immunity.
Currently, an active area of investigation to control pertussis resurgence is development of a next-generation acellular pertussis vaccine (aPV) with an optimal combination of novel adjuvants and antigens to mimic the immune response elicited by the whole-cell pertussis vaccine (wPV)9. Using the protocol described, we recently reported that the modification of a current FDA-approved aPV by the addition of a novel adjuvant, Bordetella colonization factor A (BcfA), resulted in more efficient reduction of B. pertussis bacterial load from mouse lungs10,11. This increased protection was accompanied by the skewing of an alum-induced Th1/Th2 immune response to the more protective Th1/Th17 immune profile10. This protocol is detailed and comprehensive, enabling the investigator to obtain maximal information through concurrent evaluation of host and immune responses to a variety of pathogens.
The protocol described here follows the representative vaccine schedule, shown in Figure 1, to ensure optimal host immune responses.

<table><tbody><tr><td>2L induction chamber</td><td>Vet Equip</td><td>941444</td><td></td></tr><tr><td>Fluriso</td><td>Vet One</td><td>V1 501017</td><td>any brand is appropriate</td></tr><tr><td>Bordet Gengou Agar Base</td><td>BD bioscience</td><td>248200</td><td></td></tr><tr><td>Casein</td><td>Sigma</td><td>C-7078</td><td></td></tr><tr><td>Casamino acids</td><td>VWR</td><td>J851-500G</td><td>Strainer Scholte (SS) media components</td></tr><tr><td>L-Glutamic acid</td><td>Research Products Int</td><td>G36020-500</td><td></td></tr><tr><td>L-Proline</td><td>Research Products Int</td><td>P50200-500</td><td></td></tr><tr><td>Sodium Chloride</td><td>Fisher</td><td>BP358-10</td><td></td></tr><tr><td>Potassium Phosphate monobasic</td><td>Fisher</td><td>BP362-1</td><td></td></tr><tr><td>Potassium Chloride</td><td>Fisher</td><td>P217-500</td><td></td></tr><tr><td>Magnesium Chloride hexahydrate</td><td>Fisher</td><td>M2670-500G</td><td></td></tr><tr><td>Calcium Chloride</td><td>Fisher</td><td>C75-500</td><td></td></tr><tr><td>Tris base</td><td>Fisher</td><td>BP153-1</td><td></td></tr><tr><td>L-cysteine HCl</td><td>Fisher</td><td>BP376-100</td><td>SS media suplements</td></tr><tr><td>Ferrous Sulfate heptahydrate</td><td>Sigma</td><td>F-7002</td><td></td></tr><tr><td>Niacin</td><td>Research Products Int</td><td>N20080-100</td><td></td></tr><tr><td>Glutathione</td><td>Research Products Int</td><td>G22010-25</td><td></td></tr><tr><td>Ascorbic acid</td><td>Research Products Int</td><td>A50040-500</td><td></td></tr><tr><td>RPMI 1640</td><td>ThermoFisher Scientific</td><td>11875093</td><td></td></tr><tr><td>FBS</td><td>Sigma</td><td>F2442-500mL</td><td>&amp;nbsp;any US source, non-heat inactivated</td></tr><tr><td>gentamicin</td><td>ThermoFisher Scientific</td><td>15710064</td><td></td></tr><tr><td>B-mercaptoethanol</td><td>Fisher&amp;nbsp;</td><td>BP176-100</td><td></td></tr><tr><td>15mL dounce tissue grinder</td><td>Wheaton</td><td>357544</td><td>any similar brand is appropriate</td></tr><tr><td>Cordless Hand Homogenizer</td><td>Kontes/Sigma&amp;nbsp;</td><td>Z359971-1EA</td><td>any similar brand is appropriate</td></tr><tr><td>Instruments - scissors, curve scissors, forceps, fine forceps, triangle spreaders</td><td></td><td></td><td>any brand is appropriate</td></tr><tr><td>3mL syringes</td><td>BD bioscience</td><td>309657</td><td></td></tr><tr><td>15mL conical tubes</td><td>Fisher&amp;nbsp;</td><td>339651</td><td></td></tr><tr><td>1.5mL microfuge tubes</td><td>Denville</td><td>C2170</td><td></td></tr><tr><td>70um cell strainers</td><td>Fisher&amp;nbsp;</td><td>22363548</td><td></td></tr><tr><td>60mm plates</td><td>ThermoFisher Scientific</td><td>130181</td><td></td></tr><tr><td>48-well tissue culture plates</td><td>ThermoFisher Scientific</td><td>08-772-1C</td><td></td></tr><tr><td>1mL insulin syringe 28G1/2</td><td>Fisher Scientific/Excel Int.</td><td>14-841-31</td><td></td></tr><tr><td>Mouse IFN-gamma ELISA Ready-SET-Go! Kit</td><td>Invitrogen / eBioscience</td><td>50-173-21</td><td></td></tr><tr><td>Mouse IL-17 ELISA Ready-SET-Go! Kit</td><td>Invitrogen / eBioscience</td><td>50-173-77</td><td></td></tr><tr><td>Mouse IL-5 ELISA Ready-SET-Go! Kit</td><td>Invitrogen / eBioscience</td><td>50-172-09</td><td></td></tr></tbody></table>

evaluation of host-pathogen responses and vaccine efficacy in mice

Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice

Vaccines are a 20th century medical marvel. They have dramatically reduced the morbidity and mortality caused by infectious diseases and contributed to a striking increase in life expectancy around the globe. Nonetheless, determining vaccine efficacy remains a challenge. Emerging evidence suggests that the current acellular vaccine (aPV) for Bordetella pertussis (B. pertussis) induces suboptimal immunity. Therefore, a major challenge is designing a next-generation vaccine that induces protective immunity without the adverse side effects of a whole-cell vaccine (wPV). Here we describe a protocol that we used to test the efficacy of a promising, novel adjuvant that skews immune responses to a protective Th1/Th17 phenotype and promotes a better clearance of a B. pertussis challenge from the murine respiratory tract. This article describes the protocol for mouse immunization, bacterial inoculation, tissue harvesting, and analysis of immune responses. Using this method, within our model, we have successfully elucidated crucial mechanisms elicited by a promising, next-generation acellular pertussis vaccine. This method can be applied to any infectious disease model in order to determine vaccine efficacy.

The model described shows a method to evaluate vaccine efficiency and immune responses during host-pathogen interactions. Figure 1 depicts the representative vaccine schedule used to immunize and infect mice and harvest tissues for analysis. Figure 2 demonstrates the setup of the anesthesia system employed to induce mice, enabling investigators to deliver immunizations and bacterial inoculums. Figure 3</stron...

Here we present an elegant protocol for in vivo evaluation of vaccine effectiveness and host immune responses. This protocol can be adapted for vaccine models that study viral, bacterial, or parasitic pathogens.

Vaccines are a 20th century medical marvel. They have dramatically reduced the morbidity and mortality caused by infectious diseases and contributed to a ...

evaluation-of-host-pathogen-responses-and-vaccine-efficacy-in-mice

Research

JoVE Journal

Immunology and Infection

In this video, we describe a protocol to test the efficacy of an acellular pertussis vaccine against Bordetella pertussis infection in mice. Post-vaccination, the mice were subjected to infection, and their tissue homogenate was cultured to analyze the bacterial colonies as a readout of the vaccine-induced protective immunity.

Evaluation of Vaccine-Induced Immunity Against Bacterial Infection in a Mouse Model

The host immune response to pathogen infection is a tightly regulated process. Utilizing a lipopolysaccharide lung exposure model in mice, it is possible to conduct high resolution evaluations of the complex mechanisms associated with disease pathogenesis.

The Utilization of Oropharyngeal Intratracheal PAMP Administration and Bronchoalveolar Lavage to Evaluate the Host Immune Response in Mice

Animal models have proven to be invaluable tools in defining host and pathogen specific mechanisms that contribute to the development of chronic inflammation. Here we describe a mouse model of oral infection with the human pathogen Porphyromonas gingivalis and detail methodologies to assess the progression of inflammation at local and systemic sites.

A Mouse Model for Pathogen-induced Chronic Inflammation at Local and Systemic Sites

We herein detail the methodology followed to compare protective efficacy and lung immune response induced by intranasal and subcutaneous immunization with BCG in mouse model. Our results show the benefits of pulmonary vaccination and suggest a role for IL17-mediated response in vaccine-induced protection.

Protective Efficacy and Pulmonary Immune Response Following Subcutaneous and Intranasal BCG Administration in Mice

This protocol describes how to inoculate C57BL/6J mice with the EGD strain of Listeria monocytogenes (L. monocytogenes) and to measure interferon-γ (IFN-γ) responses by natural killer (NK) cells, natural killer T (NKT) cells, and adaptive T lymphocytes post-infection. This protocol also describes how to conduct survival studies in mice after infection with a modified LD50 dose of the pathogen.

Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-&#947; Responses

Influenza A viruses (IAVs) are important human respiratory pathogens. To understand the pathogenicity of IAVs and to perform preclinical testing of novel vaccine approaches, animal models mimicking human physiology are required. Here, we describe techniques to evaluate IAV pathogenesis, humoral responses and vaccine efficacy using a mouse model of infection.

Influenza A Virus Studies in a Mouse Model of Infection

We present here an application for a standard immunological technique (CFSE stained OT-I proliferation) intended to rapidly monitor adjuvant-mediated cytotoxic T lymphocyte (CTL) generation in vivo. This fast estimation of CTL capacities is useful for the development of prophylactic vaccines against intracellular pathogens as well as therapeutic cancer vaccines.

Rapid In Vivo Assessment of Adjuvant's Cytotoxic T Lymphocytes Generation Capabilities for Vaccine Development

An approach is described for real-time detection of the innate immune response to cutaneous wounding and Staphylococcus aureus infection of mice. By comparing LysM-EGFP mice (which possess fluorescent neutrophils) with a LysM-EGFP crossbred immunodeficient mouse strain, we advance our understanding of infection and the development of approaches to combat infection.

A Mouse Model to Assess Innate Immune Response to Staphylococcus aureus Infection

This paper describes protocols of evaluating Tfh and GC B response in mouse model of influenza virus infection.

Evaluation of T Follicular Helper Cells and Germinal Center Response During Influenza A Virus Infection in Mice

Here, we present an effective and efficient method for rodent tail vein injections using a uniquely designed warming/restraining device. By streamlining the initiation of vasodilation and restraining processes, this protocol allows accurate and timely intravenous injections of large groups of animals with minimal distress.

A Contemporary Warming/Restraining Device for Efficient Tail Vein Injections in a Murine Fungal Sepsis Model

The present protocol prepares and evaluates the physical properties, immune response, and in vivo protective effect of a novel nanoemulsion adjuvant vaccine.

Evaluating the Immune Response of a Nanoemulsion Adjuvant Vaccine Against Methicillin-Resistant Staphylococcus aureus (MRSA) Infection

Learn to evaluate host-pathogen responses and vaccine efficacy in mice using in vivo immunization and bacterial challenge techniques. This protocol enables assessment of immune responses and bacterial burden in respiratory tissues.

Evaluation of Host-Pathogen Responses and Vaccine Efficacy in Mice

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