Cholera toxin and O-specific polysaccharide immune responses after oral cholera vaccination with Dukoral in different age groups of Bangladeshi participants.

Vaccination is important to prevent cholera. There are limited data comparing anti-O-specific polysaccharide (OSP) and anti-cholera toxin-specific immune responses following oral whole-cell with cholera toxin B-subunit (WC-rBS) vaccine (Dukoral, Valneva) administration in different age groups. An understanding of the differences is relevant because young children are less well protected by oral cholera vaccines than older children and adults. We compared responses in 50 adults and 49 children (ages 2 to <18) who were administered two doses of WC-rBS at a standard 14-day interval. All age groups had significant IgA and IgG plasma-blast responses to the OSP and cholera toxin B-subunit (CtxB) antigens that peaked 7 days after vaccination. However, in adults and older children (ages 5 to <18), antibody responses directed at the OSP antigen were largely IgA and IgG, with a minimal IgM response, while younger children (ages 2 to <5) mounted significant increases in IgM with minimal increases in IgA and IgG antibody responses 30 days after vaccination. In adults, anti-OSP and CtxB memory B-cell responses were detected after completion of the vaccination series, while children only mounted CtxB-specific IgG memory B-cell responses and no OSP-memory B-cell responses. In summary, children and adults living in a cholera endemic area mounted different responses to the WC-rBS vaccine, which may be a result of more prior exposure to Vibrio cholerae in older participants. The absence of class-switched antibody responses and memory B-cell responses to OSP may explain why protection wanes more rapidly after vaccination in young children compared to older vaccinees.IMPORTANCEVaccination is an important strategy to prevent cholera. Though immune responses targeting the OSP of V. cholerae are believed to mediate protection against cholera, there are limited data on anti-OSP responses after vaccination in different age groups, which is important as young children are not well protected by current oral cholera vaccines. In this study, we found that adults mounted memory B-cell responses to OSP, which were not seen in children. Adults and older children mounted class-switched (IgG and IgA) serum antibody responses to OSP, which were not seen in young children who had only IgM responses to OSP. The lack of class-switched antibody responses and memory B-cell responses to OSP in younger participants may be due to lack of prior exposure to V. cholerae and could explain why protection wanes more rapidly after vaccination in young children.

Exploring the Therapeutic Effect of Neurotrophins and Neuropeptides in Neurodegenerative Diseases: at a Glance.

Neurotrophins and neuropeptides are the essential regulators of peripheral nociceptive nerves that help to induce, sensitize, and maintain pain. Neuropeptide has a neuroprotective impact as it increases trophic support, regulates calcium homeostasis, and reduces excitotoxicity and neuroinflammation. In contrast, neurotrophins target neurons afflicted by ischemia, epilepsy, depression, and eating disorders, among other neuropsychiatric conditions. Neurotrophins are reported to inhibit neuronal death. Strategies maintained for "brain-derived neurotrophic factor (BDNF) therapies" are to upregulate BDNF levels using the delivery of protein and genes or compounds that target BDNF production and boosting BDNF signals by expanding with BDNF mimetics. This review discusses the mechanisms of neurotrophins and neuropeptides against acute neural damage as well as highlighting neuropeptides as a potential therapeutic agent against Parkinson's disease (PD), Huntington's disease (HD), Alzheimer's disease (AD), and Machado-Joseph disease (MJD), the signaling pathways affected by neurotrophins and their receptors in both standard and diseased CNS systems, and future perspectives that can lead to the potent application of neurotrophins and neuropeptides in neurodegenerative diseases (NDs).

COVID-19: The Many Ways to Hurt Your Heart.

Coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has become a global pandemic, affecting the lives of billions of individuals [...].

Emerging Role of Neuron-Glia in Neurological Disorders: At a Glance.

Based on the diverse physiological influence, the impact of glial cells has become much more evident on neurological illnesses, resulting in the origins of many diseases appearing to be more convoluted than previously happened. Since neurological disorders are often random and unknown, hence the construction of animal models is difficult to build, representing a small fraction of people with a gene mutation. As a result, an immediate necessity is grown to work within in vitro techniques for examining these illnesses. As the scientific community recognizes cell-autonomous contributions to a variety of central nervous system illnesses, therapeutic techniques involving stem cells for treating neurological diseases are gaining traction. The use of stem cells derived from a variety of sources is increasingly being used to replace both neuronal and glial tissue. The brain's energy demands necessitate the reliance of neurons on glial cells in order for it to function properly. Furthermore, glial cells have diverse functions in terms of regulating their own metabolic activities, as well as collaborating with neurons via secreted signaling or guidance molecules, forming a complex network of neuron-glial connections in health and sickness. Emerging data reveals that metabolic changes in glial cells can cause morphological and functional changes in conjunction with neuronal dysfunction under disease situations, highlighting the importance of neuron-glia interactions in the pathophysiology of neurological illnesses. In this context, it is required to improve our understanding of disease mechanisms and create potential novel therapeutics. According to research, synaptic malfunction is one of the features of various mental diseases, and glial cells are acting as key ingredients not only in synapse formation, growth, and plasticity but also in neuroinflammation and synaptic homeostasis which creates critical physiological capacity in the focused sensory system. The goal of this review article is to elaborate state-of-the-art information on a few glial cell types situated in the central nervous system (CNS) and highlight their role in the onset and progression of neurological disorders.

Multifaceted role of polyphenols in the treatment and management of neurodegenerative diseases.

Neurodegenerative diseases (NDDs) are conditions that cause neuron structure and/or function to deteriorate over time. Genetic alterations may be responsible for several NDDs. However, a multitude of physiological systems can trigger neurodegeneration. Several NDDs, such as Huntington's, Parkinson's, and Alzheimer's, are assigned to oxidative stress (OS). Low concentrations of reactive oxygen and nitrogen species are crucial for maintaining normal brain activities, as their increasing concentrations can promote neural apoptosis. OS-mediated neurodegeneration has been linked to several factors, including notable dysfunction of mitochondria, excitotoxicity, and Ca2+ stress. However, synthetic drugs are commonly utilized to treat most NDDs, and these treatments have been known to have side effects during treatment. According to providing empirical evidence, studies have discovered many occurring natural components in plants used to treat NDDs. Polyphenols are often safer and have lesser side effects. As, epigallocatechin-3-gallate, resveratrol, curcumin, quercetin, celastrol, berberine, genistein, and luteolin have p-values less than 0.05, so they are typically considered to be statistically significant. These polyphenols could be a choice of interest as therapeutics for NDDs. This review highlighted to discusses the putative effectiveness of polyphenols against the most prevalent NDDs.

Investigating Polyphenol Nanoformulations for Therapeutic Targets against Diabetes Mellitus.

Diabetes mellitus (DM) is a fatal metabolic disorder, and its prevalence has escalated in recent decades to a greater extent. Since the incidence and severity of the disease are constantly increasing, plenty of therapeutic approaches are being considered as a promising solution. Many dietary polyphenols have been reported to be effective against diabetes along with its accompanying vascular consequences by targeting multiple therapeutic targets. Additionally, the biocompatibility of these polyphenols raises questions about their use as pharmacological mediators. Nevertheless, the pharmacokinetic and biopharmaceutical properties of these polyphenols limit their clinical benefit as therapeutics. Pharmaceutical industries have attempted to improve compliance and therapeutic effects. However, nanotechnological approaches to overcome the pharmacokinetic and biopharmaceutical barriers associated with polyphenols as antidiabetic medications have been shown to be effective to improve clinical compliance and efficacy. Therefore, this review highlighted a comprehensive and up-to-date assessment of polyphenol nanoformulations in the treatment of diabetes and vascular consequences.

Seroprevalence of SARS-CoV-2 antibodies in Bangladesh related to novel coronavirus infection.

Design: A cross-sectional study was conducted amongst household members in 32 districts of Bangladesh to build knowledge about disease epidemiology and seroepidemiology of coronavirus disease 2019 (COVID-19). Objective: Antibody responses to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) were assessed in people between April and October 2020. Results: The national seroprevalence rates of immunoglobulin G (IgG) and IgM were estimated to be 30.4% and 39.7%, respectively. In Dhaka, the seroprevalence of IgG was 35.4% in non-slum areas and 63.5% in slum areas. In areas outside of Dhaka, the seroprevalence of IgG was 37.5% in urban areas and 28.7% in rural areas. Between April and October 2020, the highest seroprevalence rate (57% for IgG and 64% for IgM) was observed in August. IgM antibody was more prevalent in younger participants, while older participants had more frequent IgG seropositivity. Follow-up specimens from patients with COVID-19 and their household members suggested that both IgG and IgM seropositivity increased significantly at day 14 and day 28 compared with day 1 after enrolment. Conclusions: SARS-CoV-2 had spread extensively in Bangladesh by October 2020. This highlights the importance of monitoring seroprevalence data, particularly with the emergence of new SARS-CoV-2 variants over time.

The impact of wood dust on pulmonary function and blood immunoglobulin E, erythrocyte sedimentation rate, and C- reactive protein: A cross-sectional study among sawmill workers in Tangail, Bangladesh.

Background and Aims: Occupational exposure to wood dust leads to lung function abnormalities that are prominent causes of morbidity and disability of sawmill workers. The adverse respiratory effects of wood dust in sawmills have not been studied thoroughly in Bangladesh. This study aimed to investigate the effect of wood dust on the respiratory health of sawmill workers compared to controls as well as to determine the association of wood dust-exposing effects with inflammatory blood biomarkers, such as immunoglobulin E (IgE), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). Methods: This cross-sectional study included 100 sawmill workers from 25 distinct sawmills in various areas of Tangail, Bangladesh as well as 100 healthy volunteers who were adopted as a control group. Questionaries' survey and pulmonary function tests were performed face to face. Furthermore, after performing lung function tests, blood was drawn for further IgE, ESR, and CRP analyses. Results: Respiratory symptoms including breathlessness (32%), coughing (39%), sneezing (43%), chest tightness (30%), and itching (40%) were significantly higher in sawmill workers compared with control. Besides, sawmill workers' exposure to wood dust revealed a significantly lower level of spirometry parameters (forced vital capacity ​​​​​[FVC], FVC (%), forced expiratory volume in 1 s [FEV1], FEV1 (%), peak expiratory flow [PEF], PEF (%), FEV1/FVC (%), FEF25, FEF75, and FEF2575) compared with control and these spirometry parameters decreased with the increasing length of service. Moreover, a significantly higher level of IgE was observed in sawmill workers (290.90 ± 39.49) than in the control (120.95 ± 23.00). The high level of IgE suggests that the lower pulmonary function may be linked to allergic responses to wood dust among sawmill workers. Conclusion: This study suggested that exposure to wood dust can cause impairment of respiratory function along with high IgE levels.

Understanding the omicron variant (B.1.1.529) of SARS-CoV-2: Mutational impacts, concerns, and the possible solutions.

Despite many nations' best efforts to contain the so-called COVID-19 pandemic, the emergence of the SARS-CoV-2 Omicron strain (B.1.1.529) has been identified as a serious concern. After more than two years of COVID-19 pandemic and more than a year of worldwide vaccination efforts, the globe will not be free of COVID-19 variants such as Delta and Omicron variants. According to current statistics, the Omicron variant has more than 30 mutations when contrasted to other VOCs such as Alpha (B.1.1.7), Beta (B.1.351), and Delta (B.1.617.2). High numbers of changes, particularly in the spike protein (S-Protein), raise worries about the virus's capacity to resist pre-existing immunity acquired by vaccination or spontaneous infection and antibody-based therapy. The Omicron variant raised international concerns, resuming travel bans and coming up with many questions about its severity, transmissibility, testing, detection, and vaccines efficiency against it. Additionally, inadequate health care infrastructures and many immunocompromised individuals increase the infection susceptibility. The current status of low vaccination rates will play a significant role in omicron spreading and create a fertile ground for producing new variants. As a result, this article emphasizes the mutational changes and their consequences. In addition, the potential preventing measures have been examined in detail.

Pharmacological Potential of Avicennia alba Leaf Extract: An Experimental Analysis Focusing on Antidiabetic, Anti-inflammatory, Analgesic, and Antidiarrheal Activity.

Avicennia alba is a mangrove plant that is extensively used to treat severe health issues. This focus of this study was to investigate the antidiabetic, anti-inflammatory, analgesic, and antidiarrheal activities of methanolic extract of A. alba leaves in Swiss albino mouse model. The antidiabetic, anti-inflammatory, analgesic, and antidiarrheal activities of the leaf extract were performed using alloxan-monohydrate, carrageenan-induced paw edema, acetic acid-induced writhing test and the hot plate method, and castor oil-induced method, respectively. The extract was used at doses ranging from 200 to 500 mg/kg to conduct the investigation. Leaf extract at 400 and 500 mg/kg showed potent antidiabetic activity in alloxan-induced diabetic mice. Advanced research is needed to control blood glucose levels and carrageenan paw edema-based anti-inflammatory effects. Both tests showed statistically significant result in a dose-dependent manner. The maximum dose (500 mg/kg) demonstrated potent analgesic activity in both writhing test and hot plate method. The plant extract also showed significant antidiarrheal activity at 400 and 500 mg/kg in experimental mice. However, more research is needed to explore the possible mechanisms and isolate the compounds associated with these bioactivities from the leaf extract of A. alba.

Resveratrol and neuroprotection: an insight into prospective therapeutic approaches against Alzheimer's disease from bench to bedside.

Alzheimer's disease (AD) is the most common cause of dementia and cognitive impairment; yet, there is currently no treatment. A buildup of Aß, tau protein phosphorylation, oxidative stress, and inflammation in AD is pathogenic. The accumulation of amyloid-beta (Aß) peptides in these neurocognitive areas is a significant characteristic of the disease. Therefore, inhibiting Aß peptide aggregation has been proposed as the critical therapeutic approach for AD treatment. Resveratrol has been demonstrated in multiple studies to have a neuroprotective, anti-inflammatory, and antioxidant characteristic and the ability to minimize Aß peptides aggregation and toxicity in the hippocampus of Alzheimer's patients, stimulating neurogenesis and inhibiting hippocampal degeneration. Furthermore, resveratrol's antioxidant effect promotes neuronal development by activating the silent information regulator-1 (SIRT1), which can protect against the detrimental effects of oxidative stress. Resveratrol-induced SIRT1 activation is becoming more crucial in developing novel therapeutic options for AD and other diseases that have neurodegenerative characteristics. This review highlighted a better knowledge of resveratrol's mechanism of action and its promising therapeutic efficacy in treating AD. We also highlighted the therapeutic potential of resveratrol as an AD therapeutic agent, which is effective against neurodegenerative disorders.

Transmission of SARS-CoV-2 in the Population Living in High- and Low-Density Gradient Areas in Dhaka, Bangladesh.

Community transmission of SARS-CoV-2 in densely populated countries has been a topic of concern from the beginning of the pandemic. Evidence of community transmission of SARS-CoV-2 according to population density gradient and socio-economic status (SES) is limited. In June−September 2020, we conducted a descriptive longitudinal study to determine the community transmission of SARS-CoV-2 in high- and low-density areas in Dhaka city. The Secondary Attack Rate (SAR) was 10% in high-density areas compared to 20% in low-density areas. People with high SES had a significantly higher level of SARS-CoV-2-specific Immunoglobulin G (IgG) antibodies on study days 1 (p = 0.01) and 28 (p = 0.03) compared to those with low SES in high-density areas. In contrast, the levels of seropositivity of SARS-CoV-2-specific Immunoglobulin M (IgM) were comparable (p > 0.05) in people with high and low SES on both study days 1 and 28 in both high- and low-density areas. Due to the similar household size, no differences in the seropositivity rates depending on the population gradient were observed. However, people with high SES showed higher seroconversion rates compared to people with low SES. As no difference was observed based on population density, the SES might play a role in SARS-CoV-2 transmission, an issue that calls for further in-depth studies to better understand the community transmission of SARS-CoV-2.

Bioactive Compounds and Their Derivatives: An Insight into Prospective Phytotherapeutic Approach against Alzheimer's Disease.

Alzheimer's disease (AD) is a common neurodegenerative brain disorder that causes cellular response alterations, such as impaired cholinergic mechanism, amyloid-beta (Aß) AD aggregation, neuroinflammation, and several other pathways. AD is still the most prevalent form of dementia and affects many individuals across the globe. The exact cause of the disorder is obscure. There are yet no effective medications for halting, preventing, or curing AD's progress. Plenty of natural products are isolated from several sources and analyzed in preclinical and clinical settings for neuroprotective effects in preventing and treating AD. In addition, natural products and their derivatives have been promising in treating and preventing AD. Natural bioactive compounds play an active modulatory role in the pathological molecular mechanisms of AD development. This review focuses on natural products from plant sources and their derivatives that have demonstrated neuroprotective activities and maybe promising to treat and prevent AD. In addition, this article summarizes the literature pertaining to natural products as agents in the treatment of AD. Rapid metabolism, nonspecific targeting, low solubility, lack of BBB permeability, and limited bioavailability are shortcomings of most bioactive molecules in treating AD. We can use nanotechnology and nanocarriers based on different types of approaches.

Neuropharmacological and Antidiabetic Potential of Lannea coromandelica (Houtt.) Merr. Leaves Extract: An Experimental Analysis.

The present study examines the neuropharmacological and antidiabetic properties of methanol leaves extract of Lannea coromandelica in animal models. This study is carried out by elevated plus-maze apparatus, motor coordination, thiopental sodium has an induction role in sleeping time, hole board, hole cross, open field, antidiabetic studies. Mice were treated doses of 100, 150, and 200 mg/kg body weight in elevated plus-maze apparatus and motor coordination; 100 and 200 mg/kg body weight in sleeping time, hole cross, hole board, and open field tests; and 200 and 400 mg/kg body weight in the antidiabetic activity test. Extraction specifies a significantly decreased time duration and sleeping time in a thiopental sodium-induced sleeping time test. The experimental extract decreased locomotor and exploratory behaviors of mice in the open-field and hole-cross tests compared to the effects of the control. Furthermore, the extract increased sleeping time with a dose-dependent onset of action. The hole-board test extract also demonstrated a reduced number of head dips. The findings showed that L. coromandelica has potential neuropharmacological effects. In addition, in alloxan-induced diabetic mice, leaves extract at 200 and 400 mg/kg body weight revealed significant antidiabetic properties and could be used to manage blood glucose levels with more research.

Natural Small Molecules in Breast Cancer Treatment: Understandings from a Therapeutic Viewpoint.

Breast cancer (BrCa) is the most common malignancy in women and the second most significant cause of death from cancer. BrCa is one of the most challenging malignancies to treat, and it accounts for a large percentage of cancer-related deaths. The number of cases requiring more effective BrCa therapy has increased dramatically. Scientists are looking for more productive agents, such as organic combinations, for BrCa prevention and treatment because most chemotherapeutic agents are linked to cancer metastasis, the resistance of the drugs, and side effects. Natural compounds produced by living organisms promote apoptosis and inhibit metastasis, slowing the spread of cancer. As a result, these compounds may delay the spread of BrCa, enhancing survival rates and reducing the number of deaths caused by BrCa. Several natural compounds inhibit BrCa production while lowering cancer cell proliferation and triggering cell death. Natural compounds, in addition to therapeutic approaches, are efficient and potential agents for treating BrCa. This review highlights the natural compounds demonstrated in various studies to have anticancer properties in BrCa cells. Future research into biological anti-BrCa agents may pave the way for a new era in BrCa treatment, with natural anti-BrCa drugs playing a key role in improving BrCa patient survival rates.

Exploring the Journey of Zinc Oxide Nanoparticles (ZnO-NPs) toward Biomedical Applications.

The field of nanotechnology is concerned with the creation and application of materials having a nanoscale spatial dimensioning. Having a considerable surface area to volume ratio, nanoparticles have particularly unique properties. Several chemical and physical strategies have been used to prepare zinc oxide nanoparticles (ZnO-NPs). Still, biological methods using green or natural routes in various underlying substances (e.g., plant extracts, enzymes, and microorganisms) can be more environmentally friendly and cost-effective than chemical and/or physical methods in the long run. ZnO-NPs are now being studied as antibacterial agents in nanoscale and microscale formulations. The purpose of this study is to analyze the prevalent traditional method of generating ZnO-NPs, as well as its harmful side effects, and how it might be addressed utilizing an eco-friendly green approach. The study's primary focus is on the potential biomedical applications of green synthesized ZnO-NPs. Biocompatibility and biomedical qualities have been improved in green-synthesized ZnO-NPs over their traditionally produced counterparts, making them excellent antibacterial and cancer-fighting drugs. Additionally, these ZnO-NPs are beneficial when combined with the healing processes of wounds and biosensing components to trace small portions of biomarkers linked with various disorders. It has also been discovered that ZnO-NPs can distribute and sense drugs. Green-synthesized ZnO-NPs are compared to traditionally synthesized ones in this review, which shows that they have outstanding potential as a potent biological agent, as well as related hazardous properties.

Correction: Plasma and memory B cell responses targeting O-specific polysaccharide (OSP) are associated with protection against Vibrio cholerae O1 infection among household contacts of cholera patients in Bangladesh.

[This corrects the article DOI: 10.1371/journal.pntd.0006399.].

Defining Polysaccharide-Specific Antibody Targets against Vibrio cholerae O139 in Humans following O139 Cholera and following Vaccination with a Commercial Bivalent Oral Cholera Vaccine, and Evaluation of Conjugate Vaccines Targeting O139.

Cholera caused by Vibrio cholerae O139 could reemerge, and proactive development of an effective O139 vaccine would be prudent. To define immunoreactive and potentially immunogenic carbohydrate targets of Vibrio cholerae O139, we assessed immunoreactivities of various O-specific polysaccharide (OSP)-related saccharides with plasma from humans hospitalized with cholera caused by O139, comparing responses to those induced in recipients of a commercial oral whole-cell killed bivalent (O1 and O139) cholera vaccine (WC-O1/O139). We also assessed conjugate vaccines containing selected subsets of these saccharides for their ability to induce protective immunity using a mouse model of cholera. We found that patients with wild-type O139 cholera develop IgM, IgA, and IgG immune responses against O139 OSP and many of its fragments, but we were able to detect only a moderate IgM response to purified O139 OSP-core, and none to its fragments, in immunologically naive recipients of WC-O1/O139. We found that immunoreactivity of O139-specific polysaccharides with antibodies elicited by wild-type infection markedly increase when saccharides contain colitose and phosphate residues, that a synthetic terminal tetrasaccharide fragment of OSP is more immunoreactive and protectively immunogenic than complete OSP, that native OSP-core is a better protective immunogen than the synthetic OSP lacking core, and that functional vibriocidal activity of antibodies predicts in vivo protection in our model but depends on capsule thickness. Our results suggest that O139 OSP-specific responses are not prominent following vaccination with a currently available oral cholera vaccine in immunologically naive humans and that vaccines targeting V. cholerae O139 should be based on native OSP-core or terminal tetrasaccharide. IMPORTANCE Cholera is a severe dehydrating illness of humans caused by Vibrio cholerae serogroup O1 or O139. Protection against cholera is serogroup specific, and serogroup specificity is defined by O-specific polysaccharide (OSP). Little is known about immunity to O139 OSP. In this study, we used synthetic fragments of the O139 OSP to define immune responses to OSP in humans recovering from cholera caused by V. cholerae O139, compared these responses to those induced by the available O139 vaccine, and evaluated O139 fragments in next-generation conjugate vaccines. We found that the terminal tetrasaccharide of O139 is a primary immune target but that the currently available bivalent cholera vaccine poorly induces an anti-O139 OSP response in immunologically naive individuals.

Parenteral Vaccination with a Cholera Conjugate Vaccine Boosts Vibriocidal and Anti-OSP Responses in Mice Previously Immunized with an Oral Cholera Vaccine.

Oral cholera vaccination protects against cholera; however, responses in young children are low and of short duration. The best current correlates of protection against cholera target Vibrio cholerae O-specific polysaccharide (anti-OSP), including vibriocidal responses. A cholera conjugate vaccine has been developed that induces anti-OSP immune responses, including memory B-cell responses. To address whether cholera conjugate vaccine would boost immune responses following oral cholera vaccination, we immunized mice with oral cholera vaccine Inaba CVD 103-HgR or buffer only (placebo) on day 0, followed by parenteral boosting immunizations on days 14, 42, and 70 with cholera conjugate vaccine Inaba OSP: recombinant tetanus toxoid heavy chain fragment or phosphate buffered saline (PBS)/placebo. Compared with responses in mice immunized with oral vaccine alone or intramuscular cholera conjugate vaccine alone, mice receiving combination vaccination developed significantly higher vibriocidal, IgM OSP-specific serum responses and OSP-specific IgM memory B-cell responses. A combined vaccination approach, which includes oral cholera vaccination followed by parenteral cholera conjugate vaccine boosting, results in increased immune responses that have been associated with protection against cholera. These results suggest that such an approach should be evaluated in humans.