Medicine and Health Sciences Commons^™

Evaluation Of The Efficacy Of Synthetic Glycovaccines Against Both Murine Acute Chagas Disease And Cutaneous Leishmaniasis, Colin D. Knight

Open Access Theses & Dissertations

Chagas disease (CD) and cutaneous leishmaniasis (CL) are neglected tropical diseases caused by the protozoan trypanosomatids, Trypanosoma cruzi and Leishmania spp., respectively. There are approximately 6-8 million people infected with T. cruzi worldwide and ~300,000 people in the US. Between 700,000 and 1.2 million new cases of CL occur worldwide yearly. The approved chemotherapies for both diseases are partially effective and may cause serious adverse events, resulting in premature treatment interruption. Moreover, no effective vaccine for either disease is available. Therefore, developing a vaccine that would provide effective cross-protection against both diseases would provide a cost-effective alternative to the existing …

Adjuvanted Fusion Protein Vaccine Induces Durable Immunity To Onchocerca Volvulus In Mice And Non-Human Primates, Nathan M. Ryan, Jessica A. Hess, Erica J. Robertson, Nancy Tricoche, Cheri Turner, Jenn Davis, Nikolai Petrovsky, Melissa Ferguson, William J. Rinaldi, Valerie M. Wong, Ayako Shimada, Bin Zhan, Maria Elena Bottazzi, Benjamin L. Makepece, Sean A. Gray, Darrick Carter, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

Onchocerciasis remains a debilitating neglected tropical disease. Due to the many challenges of current control methods, an effective vaccine against the causative agent Onchocerca volvulus is urgently needed. Mice and cynomolgus macaque non-human primates (NHPs) were immunized with a vaccine consisting of a fusion of two O. volvulus protein antigens, Ov-103 and Ov-RAL-2 (Ov-FUS-1), and three different adjuvants: Advax-CpG, alum, and AlT4. All vaccine formulations induced high antigen-specific IgG titers in both mice and NHPs. Challenging mice with O. volvulus L3 contained within subcutaneous diffusion chambers demonstrated that Ov-FUS-1/Advax-CpG-immunized animals developed protective immunity, durable for at least 11 weeks. Passive …

Adenoviral-Vectored Epigraph Vaccine Elicits Robust, Durable, And Protective Immunity Against H3 Influenza A Virus In Swine, Erika M. Petro-Turnquist, Matthew J. Pekarek, Nicholas Jeanjaquet, Cedric Wooledge, David J. Steffen, Hiep Vu, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Current methods of vaccination against swine Influenza A Virus (IAV-S) in pigs are infrequently updated, induce strain-specific responses, and have a limited duration of protection. Here, we characterize the onset and duration of adaptive immune responses after vaccination with an adenoviral-vectored Epigraph vaccine. In this longitudinal study we observed robust and durable antibody responses that remained above protective titers six months after vaccination. We further identified stable levels of antigen-specific T cell responses that remained detectable in the absence of antigen stimulation. Antibody isotyping revealed robust class switching from IgM to IgG induced by Epigraph vaccination, while the commercial comparator …

Effects Of Adjuvants In A Rabies-Vectored Ebola Virus Vaccine On Protection From Surrogate Challenge, Catherine Yankowski, Drishya Kurup, Christoph Wirblich, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50-90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

A Monovalent Mt10-Cvb3 Vaccine Prevents Cvb4-Accelerated Type 1 Diabetes In Nod Mice, Mahima T. Rasquinha, Ninaad Lasrado, Meghna Sur, Kiruthiga Mone, Haowen Qiu, Jean-Jack Riethoven, Raymond A. Sobel, Jay Reddy

Nebraska Center for Virology: Faculty Publications

Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in …

Rates And Perceptions Of Covid-19 Vaccination From University Of Mississippi Students, Josie Parham

Honors Theses

The trials, tribulations and triumphs of the global COVID-19 pandemic are impacted by and are a product of behaviors that occur at the level of nations, states, cities and, ultimately, communities. In the wake of the development of safe and effective vaccines against SARS-CoV2, the virus responsible for the pandemic, the significance of the vaccine is closely linked to the number of individuals that receive the vaccine. To date, surveys have measured sizable variations in vaccination rates between nations, states, cities, and communities. Focusing on events that have transpired in one such local community, the present study (i) measured the …

Immunogenicity And Protective Efficacy Of A Recombinant Pichinde Viral-Vectored Vaccine Expressing Influenza Virus Hemagglutinin Antigen In Pigs, Sushmita Kumari, Jayeshbhai Chaudhari, Qinfeng Huang, Phillip Gauger, Marcelo Nunes De Almeida, Yuying Liang, Hinh Ly, Hiep Vu

Nebraska Center for Virology: Faculty Publications

Influenza A virus of swine (IAV-S) is an economically important swine pathogen. The IAV-S hemagglutinin (HA) surface protein is the main target for vaccine development. In this study, we evaluated the feasibility of using the recombinant tri-segmented Pichinde virus (rPICV) as a viral vector to deliver HA antigen to protect pigs against IAV-S challenge. Four groups of weaned pigs (T01–T04) were included in the study. T01 was injected with PBS to serve as a non-vaccinated control. T02 was inoculated with rPICV expressing green fluorescence protein (rPICV-GFP). T03 was vaccinated with rPICV expressing the HA antigen of the IAV-S H3N2 strain …

Effectiveness Of Stricter Vaccine Mandates In Public Schools And Childcare Centers, Anna Ferentinos

Emerging Writers

Vaccines have been a controversial and frequently discussed topic the last two years due to the COVID-19 pandemic. The amount of readily available information on the internet - accurate or not – has led to many theories and opinions on whether to vaccinate and why, or why not. This article discusses these theories, as well as the benefits and consequences of vaccine mandates, with the help of examples from other countries. The author argues that a federal vaccine mandate should be implemented in the United States of America so as to encourage parents to protect children through scheduled immunizations.

Simian Varicella Virus Antibody Response In Recombinant Svv-Siv Immunized Primates, Kiser Horne

Honors Theses

Since its emergence in the early 1980’s HIV has killed approximately 32 million people, and continues to kill over half a million people every year. Significant research into potential vaccines and cures for HIV has been ongoing for decades but has been largely unsuccessful. One of the more promising technologies that is being investigated to develop an HIV vaccine is recombinant vaccine technology. The study presented in this thesis aims to use simian varicella virus (SVV) and simian immunodeficiency virus (SIV) to act as a model for recombinant vaccine development. If a recombinant SVV-SIV vaccine can be proven safe and …

The Aboriginal Gap In Online Active Vaccine Safety Surveillance, Patrick Cashman, Sally-Anne Munnoch, Katrina Clark, Natalie Allan, Stephen Clarke, Kristine Macartney, David Durrheim

Australian Indigenous HealthBulletin

Objectives: To investigate if Aboriginal people are equally included in new forms of vaccine safety post-marketing surveillance that support safety signal detection and confidence in the vaccine program by comparing the use of Vaxtracker active adverse events following immunisation (AEFI) surveillance between Aboriginal and non-Aboriginal parents of vaccinated children.

Methods: In 2016, automated AEFI surveillance was conducted to monitor seasonal influenza vaccine in children aged 18 months to less than 5 years and for DTPa vaccine after the inclusion of a new dose at 18 months of age. To explore reasons for non-response, Aboriginal Immunisation Officers contacted the …

Targeting Natural Killer Cells For Improved Immunity And Control Of The Adaptive Immune Response., Stephen Pierce, Eric S. Geanes, Todd Bradley

Manuscripts, Articles, Book Chapters and Other Papers

Natural killer (NK) cells are critical for targeting and killing tumor, virus-infected and stressed cells as a member of the innate immune system. Recently, NK cells have also emerged as key regulators of adaptive immunity and have become a prominent therapeutic target for cancer immunotherapy and infection control. NK cells display a diverse array of phenotypes and function. Determining how NK cells develop and are regulated is critical for understanding their role in both innate and adaptive immunity. In this review we discuss current research approaches into NK cell adaptive immunity and how these cells are being harnessed for improving …

Cervico-Vaginal Inflammatory Cytokine And Chemokine Responses To Two Different Siv Immunogens, Nikki P.L. Toledo, Hongzhao Li, Robert W. Omange, Tamara G. Dacoba, Jose Crecente-Campo, Dane Schalk, Mohammad A. Kashem, Eva Rakasz, Nancy Schultz-Darken, Qingsheng Li, James B. Whitney, Maria J. Alonso, Francis A. Plummer, Ma Luo

Nebraska Center for Virology: Faculty Publications

Studies have shown that vaccine vectors and route of immunization can differentially activate different arms of the immune system. However, the effects of different HIV vaccine immunogens on mucosal inflammation have not yet been studied. Because mucosal sites are the primary route of HIV infection, we evaluated the cervico-vaginal inflammatory cytokine and chemokine levels of Mauritian cynomolgus macaques following immunization and boost using two different SIV vaccine immunogens. The PCS vaccine delivers 12 20-amino acid peptides overlapping the 12 protease cleavage sites, and the Gag/Env vaccine delivers the full Gag and full Env proteins of simian immunodeficiency virus. We showed …

The Reemergence Of Vaccine Nationalism, Ana Santos Rutschman

All Faculty Scholarship

This short essay explores the reemergence of vaccine nationalism during the COVID-19 pandemic. The essay traces the pre-COVID origins of vaccine nationalism and explains how it can have detrimental effects on equitable access to newly developed vaccines.

Incorporating B Cell Activating Factor (Baff) Into The Membrane Of Rabies Virus (Rabv) Particles Improves The Speed And Magnitude Of Vaccine-Induced Antibody Responses., Joseph R Plummer, James P Mcgettigan

Department of Microbiology and Immunology Faculty Papers

B cell activating factor (BAFF) is a member of the tumor necrosis factor (TNF) superfamily of cytokines that links innate with adaptive immunity. BAFF signals through receptors on B cells, making it an attractive molecule to potentiate vaccine-induced B cell responses. We hypothesized that a rabies virus (RABV)-based vaccine displaying both antigen and BAFF on the surface of the same virus particle would target antigen-specific B cells for activation and improve RABV-specific antibody responses. To test this hypothesis, we constructed a recombinant RABV-based vector expressing virus membrane-anchored murine BAFF (RABV-ED51-mBAFF). BAFF was incorporated into the RABV particle and determined to …

Intranasal Peptide-Based Fpva-Klh Conjugate Vaccine Protects Mice From Pseudomonas Aeruginosa Acute Murine Pneumonia, Emel Sen-Kilic, Catherine B. Blackwood, Dylan T. Boehm, Wiliam T. Witt, Aaron C. Malkowski, Justin R. Bevere, Ting Y. Wong, Jesse M. Hall, Shelby D. Bradford, Melinda E. Varney, Fredrick Heath Damron, Mariette Barbier

Faculty & Staff Scholarship

Pseudomonas aeruginosa is an opportunistic pathogen causing acute and chronic respiratory infections associated with morbidity and mortality, especially in patients with cystic fibrosis. Vaccination against P. aeruginosa before colonization may be a solution against these infections and improve the quality of life of at-risk patients. To develop a vaccine against P. aeruginosa, we formulated a novel peptide-based P. aeruginosa subunit vaccine based on the extracellular regions of one of its major siderophore receptors, FpvA. We evaluated the effectiveness and immunogenicity of the FpvA peptides conjugated to keyhole limpet hemocyanin (KLH) with the adjuvant curdlan in a murine vaccination and challenge …

A Single-Cycle Adenovirus Type 7 Vaccine For Prevention Of Acute Respiratory Disease, Brianna L. Bullard, Brigette N. Corder, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus type 7 (Ad7) infection is associated with acute respiratory disease (ARD), especially in military recruits living in close quarters. Recently, several outbreaks of Ad7 infections have occurred in civilian populations, with some cases leading to death. However, the current Ad7 vaccine is licensed for use only in military recruits because it utilizes an orally delivered wild type virus which is shed in the stool for 28 days after immunization. This poses a safety risk due to the possibility of virus spread to vulnerable populations. To address the need for a safer Ad7 vaccine for use in civilian populations, we …

The Role Of Cd8 T Cell Immunodominance And Regulatory T Cells In Neonatal Immunity To Influenza Virus, Luke Heil

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality as well as delayed clearance of the virus. Efforts to improve influenza infection outcomes in neonates typically center on prevention, although current vaccines fall short of complete protection and can only be administered in humans after 6 months of life. We propose that as the neonatal immune system responds differently than the adult immune system, interventions that are efficacious or tolerable in adults cannot be guaranteed to perform the same in neonates. T cell vaccines that target conserved influenza virus epitopes have been proposed …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

Tryptophan 375 Stabilizes The Outer-Domain Core Of Gp120 For Hiv Vaccine Immunogen Design, Duoyi Hu, Dane Bowder, Wenzhong Wei, Jesse Thompson, Mark A. Wilson, Shi-Hua Xiang

Nebraska Center for Virology: Faculty Publications

The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a …

Vaccines And The Looming Threat Of Syphilis, Charles T. Ambrose

Microbiology, Immunology, and Molecular Genetics Faculty Publications

During the past several decades, syphilis has increased in the US and explosively so in China and Russia.While most current cases can be cured by penicillin or second line antibiotics, strains of the syphilis spirochete (Treponema pallidum) resistant to the latter have emerged.And the potential of strains to acquire resistance to penicillin via plasmids has recently been recognized.The 36 million-plus undertreated cases of syphilis in the world represent metaphorically a vast global 37°C incubator allowing exchange of antibiotic resistant genes among the human-borne bacteria and theoretically permitting the emergence of penicillin resistant strains.None has yet been identified but …

Drug And Vaccine Development For Neisseria Gonorrhoeaea, Devin R. Cash

Theses and Dissertations

Neisseria gonorrhoeae, the causative agent of the STI gonorrhea, is not preventable by vaccination and is rapidly developing resistance to antibiotics. One important strategy for gonococcal survival in the host is iron acquisition in the face of nutritional immunity. To overcome iron limitation, the gonococcus expresses TonB dependent transporters (TdTs), outer membrane proteins that facilitate nutrient acquisition. Of the TdTs, the transferrin (Tf), lactoferrin (Lf), and hemoglobin (Hb) receptors hijack iron directly from host proteins, and studies have already shown that the Tf receptor is essential for the initiation of human infection. Given that the TdTs are virulence factors, …

Vaccines Within Vaccines: The Use Of Adenovirus Types 4 And 7 As Influenza Vaccine Vectors, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Adenovirus Types 4 and 7 (Ad4 and Ad7) are associated with acute respiratory distress (ARD). In order to prevent widespread Ad-associated ARD (Ad-ARD) the United States military immunizes new recruits using a safe and effective lyophilized wildtype Ad4 and Ad7 delivered orally in an enteric-coated capsule. We cloned Ad4 and Ad7 and modified them to express either a GFP-Luciferase (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (HA1-con). BALB/c mice were injected with GFPLuc expressing viruses intramuscularly (i.m.) and intranasally (i.n.). Ad4 induced significantly higher luciferase expression levels as compared with Ad7 by both routes. Ad7 transduction was restored …

Vaccines Within Vaccines: The Use Of Adenovirus Types 4 And 7 As Influenza Vaccine Vectors, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

adenovirus Types 4 and 7 (ad4 and ad7) are associated with acute respiratory distress (aRD). In order to prevent wide- spread ad-associated aRD (ad-aRD) the United states military immunizes new recruits using a safe and effective lyophi- lized wildtype ad4 and ad7 delivered orally in an enteric-coated capsule. We cloned ad4 and ad7 and modified them to express either a GFP-Luciferase (GFPLuc) fusion gene or a centralized influenza H1 hemagglutinin (Ha1-con). BaLB/c mice were injected with GFPLuc expressing viruses intramuscularly (i.m.) and intranasally (i.n.). ad4 induced significantly higher luciferase expression levels as compared with ad7 by both routes. ad7 transduction …

Safety And Immunoreactivity Of A Xenogeneic Dna Plasmid Vaccine Expressing Human Tyrosinase In Tumor-Bearing Horses, Luis Miguel Lembcke Perez Prieto

Doctoral Dissertations

Melanomas are among the most common skin tumors in horses (second only to sarcoids), with prevalence rates reaching as high as 80% in adult gray horses. Despite the wide availability of measures of local control, there are currently no systemic therapies that can effectively prevent spread, or treat metastatic or locally advanced/non-resectable melanoma in horses. A form of gene immunotherapy based on a plasmid DNA construct containing a xenogeneic form of the antigen tyrosinase have been developed and optimized for targeting cancer in both humans and dogs; and have demonstrated significant immunoreactivity and clinical benefit in the treatment of melanocytic …

Development Of A Novel Metallo-Lipid Microparticle Delivery System For A Leishmania Mexicana Dna Vaccine Candidate, Joanna B. Valencia

Open Access Theses & Dissertations

ABSTRACT

Background and Significance.

The leishmaniases are an important group of neglected tropical parasitic diseases caused by parasitic protozoa of the genus Leishmania. International health authorities estimate that 350 million people around the world are at risk for contracting leishmaniasis. Two million new cases occur each year and 12 million people are presently infected worldwide. Leishmaniasis is endemic throughout the Americas region including all of Central America, most of South America, Mexico and southern Texas. Leishmania is also considered a threat to the military readiness of U.S. troops deployed to the Middle East or Latin America.

First- and second-line treatments …

Long-Term Immunity To Lethal Acute Or Chronic Type Ii Toxoplasma Gondii Infection Is Effectively Induced In Genetically Susceptible C57bl/6 Mice By Immunization With An Attenuated Type I Vaccine Strain, Jason P. Gigley, Barbara A. Fox, David J. Bzik

Dartmouth Scholarship

C57BL/6 (B6) mice are genetically highly susceptible to chronic type II Toxoplasma gondii infections that invariably cause lethal toxoplasmic encephalitis. We examined the ability of an attenuated type I vaccine strain to elicit long-term immunity to lethal acute or chronic type II infections in susceptible B6 mice. Mice immunized with the type I cps1-1 vaccine strain were not susceptible to a lethal (100-cyst) challenge with the type II strain ME49. Immunized mice challenged with 10 ME49 cysts exhibited significant reductions in brain cyst and parasite burdens compared to naive mice, regardless of the route of challenge infection. Remarkably, cps1-1 strain-immunized …

Lipid Nanoparticles With Accessible Nickel As A Vaccine Delivery System For Single And Multiple His-Tagged Hiv Antigens, Weili Yan, Anekant Jain, Ronan O'Carra, Jerold Woodward, Wenxue Li, Guanhan Li, Avindra Nath, Russell J. Mumper

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Lipid-based nanoparticles (NPs) with a small amount of surface-chelated nickel (Ni-NPs) were developed to easily formulate the HIV his-tagged Tat protein, as well as to formulate and co-deliver two HIV antigens (his-p24 and his-Nef) on one particle. Female BALB/c mice were immunized by s.c. injection with his-Tat/Ni-NP formulation (1.5 μg Tat-his/mouse) and control formulations on day 0 and 14. The day 28 anti-Tat specific IgG titer with his-Tat/Ni-NP was significantly greater than that with Alum/his-Tat. Furthermore, splenocytes from his-Tat/Ni-NP immunized mice secreted significantly higher IFN-γ than those from mice immunized with Alum/his-Tat. Although Ni-NPs did not show better adjuvant activity …

Prophylaxis And Therapy Of Inhalational Anthrax By A Novel Monoclonal Antibody To Protective Antigen That Mimics Vaccine-Induced Immunity, Laura Vitale, Diann Blanset, Israel Lowy, Thomas O'Neill, Joel Goldstein, Stephen F. Little, Gerard P. Andrews, Gary Dorough, Ronald K. Taylor, Tibor Keler

Dartmouth Scholarship

The neutralizing antibody response to the protective antigen (PA) component of anthrax toxin elicited by approved anthrax vaccines is an accepted correlate for vaccine-mediated protection against anthrax. We reasoned that a human anti-PA monoclonal antibody (MAb) selected on the basis of superior toxin neutralization activity might provide potent protection against anthrax. The fully human MAb (also referred to as MDX-1303 or Valortim) was chosen from a large panel of anti-PA human MAbs generated using transgenic mice immunized with recombinant PA solely on the basis of in vitro anthrax toxin neutralization. This MAb was effective in prophylactic and postsymptomatic treatment of …

Transcutaneous Immunization With Toxin-Coregulated Pilin A Induces Protective Immunity Against Vibrio Cholerae O1 El Tor Challenge In Mice, Julianne E. Rollenhagen, Anuj Kalsy, Francisca Cerda, Manohar John

Dartmouth Scholarship

Toxin-coregulated pilin A (TcpA) is the main structural subunit of a type IV bundle-forming pilus of Vibrio cholerae, the cause of cholera. Toxin-coregulated pilus is involved in formation of microcolonies of V. cholerae at the intestinal surface, and strains of V. cholerae deficient in TcpA are attenuated and unable to colonize intestinal surfaces. Anti-TcpA immunity is common in humans recovering from cholera in Bangladesh, and immunization against TcpA is protective in murine V. cholerae models. To evaluate whether transcutaneously applied TcpA is immunogenic, we transcutaneously immunized mice with 100 mug of TcpA or TcpA with an immunoadjuvant (cholera toxin [CT], …