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Cecil Czerkinsky

Cecil Czerkinsky
French National Institute of Health and Medical Research · Centre National de la Recherche Scientifique, Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France

DDS, PhD, Dr Med Sci

About

205
Publications
27,500
Reads
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13,054
Citations
Citations since 2016
18 Research Items
2888 Citations
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20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
20162017201820192020202120220100200300400
Additional affiliations
April 2014 - present
French National Institute of Health and Medical Research - Centre National de la Recherche Scientifique- Universite de Nice Sophia Antipolis
Position
  • Research Director
September 2005 - December 2012
International Vaccine Institute
Position
  • Deputy Director General

Publications

Publications (205)
Article
Full-text available
Shigella is a highly prevalent bacterium causing acute diarrhea and dysentery in developing countries. Shigella infections are treated with antibiotics but Shigellae are increasingly resistant to these drugs. Vaccination can be a countermeasure against emerging antibiotic-resistant shigellosis. Because of the structural variability in Shigellae O-a...
Article
Full-text available
Potential use of cholera toxin (CT) as a mucosal vaccine adjuvant has been documented in a variety of animal models. However, native CT is highly toxic to be used as a mucosal adjuvant in humans. Here, we demonstrate a new approach to generate a mucosal adjuvant by replacing the B subunit of CT with HIV-1 Tat protein transduction domain (PTD), whic...
Article
Full-text available
Background: Assessing immune response after rotavirus vaccination consists in measuring serum or plasma IgA and IgG antibodies, but these assays provide very little information about the mucosal immune response. Thus the development of assays for detection of mucosal immune response following rotavirus vaccination is essential. We evaluate to asses...
Article
Oral vaccine responsiveness is often lower in children in less developed countries. Childhood malnutrition may be associated with poor immune response to oral vaccines. The present study was designed to investigate whether protein energy malnutrition (PEM) impairs B cell immunity and ultimately reduces oral vaccine efficacy in a mouse model. Purifi...
Article
Full-text available
Background: The final endgame strategy of global polio eradication initiative includes switching from trivalent oral poliovirus vaccines (tOPV) to bivalent oral polio vaccine (bOPV), and introduction of inactivated poliovirus vaccine (IPV). This study compares IPV with tOPV week 39 boost in Indian infants. Methods: Starting 28 March 2012, we enroll...
Article
Full-text available
Developing countries are burdened with Shigella diarrhea. Understanding mucosal immune responses associated with natural Shigella infection is important to identify potential correlates of protection and as such to design effective vaccines. We performed a comparative analysis of circulating mucosal plasmablasts producing specific antibodies agains...
Article
Full-text available
Background The “gold standard” for assessing mucosal immunity after vaccination with poliovirus vaccines consists in measuring virus excretion in stool after challenge with oral poliovirus vaccine (OPV). This testing is time and resource intensive, and development of alternative methods is a priority for accelerating polio eradication. We therefore...
Article
Since the first licensure of the Sabin oral polio vaccine more than 50 years ago, only eight enteric vaccines have been licensed for four disease indications, and all are given orally. While mucosal vaccines offer programmatically attractive tools for facilitating vaccine deployment, their development remains hampered by several factors: -limited k...
Article
Full-text available
In developing countries Shigella is a primary cause of diarrhea in infants and young children. Although antibiotic therapy is an effective treatment for shigellosis, therapeutic options are narrowing due to the emergence of antibiotic resistance. Thus, preventive vaccination could become the most efficacious approach for controlling shigellosis. We...
Article
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Because of their large surface area and immunological competence, mucosal tissues are attractive administration and target sites for vaccination. An important characteristic of mucosal vaccination is its ability to elicit local immune responses, which act against infection at the site of pathogen entry. However, mucosal surfaces are endowed with po...
Article
Full-text available
Effector T cells are described to be primed in the lymph nodes draining the site of immunization and to recirculate to effector sites. Sublingual immunization generates effector T cells able to disseminate to the genital tract. Herein, we report an alternative mechanism that involves the recirculation of antigen-bearing dendritic cells (DCs) in rem...
Article
Full-text available
The enzyme-linked immunospot (ELISPOT) assay was originally developed to enumerate antigen-specific antibody-secreting cells (ASCs), and has subsequently been adapted for various applications, including the detection cytokine-secreting cells. Owing to its exceptionally high sensitivity, the ELISPOT has proven to be especially useful for detecting d...
Article
Full-text available
The lack of appropriate animal model for studying protective immunity has limited vaccine development against cholera. Here, we demonstrate a pulmonary cholera model conferred by intranasal administration of mice with live Vibrio cholerae. The bacterial components, but not cholera toxin, caused lethal and acute pneumonia by inducing massive inflamm...
Article
Full-text available
Background Sublingual (s.l.) administration of soluble protein antigens, inactivated viruses, or virus-like particles has been shown to induce broad immune responses in mucosal and extra-mucosal tissues. Recombinant replication-defective adenovirus vectors (rADVs) infect mucosa surface and therefore can serve as a mucosal antigen delivery vehicle....
Article
Clin Microbiol Infect 2012; 18 (Suppl. 5): 117–122 The female genital mucosa constitutes the major port of entry of sexually transmitted infections. Most genital microbial pathogens represent an enormous challenge for developing vaccines that can induce genital immunity that will prevent their transmission. It is now established that long-lasting p...
Article
Full-text available
The nonstructural protein 1 (NS1) of influenza A virus (IAV) enables the virus to disarm the host cell type 1 IFN defense system. Mutation or deletion of the NS1 gene leads to attenuation of the virus and enhances host antiviral response making such live-attenuated influenza viruses attractive vaccine candidates. Sublingual (SL) immunization with l...
Article
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Bacillus Calmette-Guérin (BCG) vaccination has proven to be efficient in immunologically naïve infants; however, it has not been investigated that maternal natural exposure to Mycobacterium and/or BCG vaccine could influence the characteristics of immune responses to BCG in newborns. In this study, we analyzed whether the maternal immune status to...
Article
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The ability of activated B cells to protect against various experimental autoimmune or allergic diseases makes them attractive for use in cell-based therapies. We describe an efficient way to generate B cells with strong suppressive functions by incubating naive B cells with a relevant Ag conjugated to cholera toxin B subunit (CTB). This allows mos...
Article
Full-text available
The ectodomain of matrix protein 2 (M2e) of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific antibodies (Abs) have been shown to display significant cross-protective activit...
Article
The Global Polio Eradication Initiative (GPEI) currently based on use of oral poliovirus vaccine (OPV) has identified suboptimal immunogenicity of this vaccine as a major impediment to eradication, with a failure to induce protection against paralytic poliomyelitis in certain population segments in some parts of the world. The Mucosal Immunity and...
Article
Since the resolution of the World Assembly in 1988 to eradicate polio globally, substantial progress toward this target has been achieved, but the final goal remains elusive. India and other tropical developing countries present a unique challenge because of the much lower oral poliovirus vaccine (OPV) immunogenicity compared to industrialized coun...
Article
Full-text available
Vibrio cholerae is a globally important pathogen that is endemic in many areas of the world and causes 3-5 million reported cases of cholera every year. Historically, there have been seven acknowledged cholera pandemics; recent outbreaks in Zimbabwe and Haiti are included in the seventh and ongoing pandemic. Only isolates in serogroup O1 (consistin...
Conference Paper
Highly pathogenic avian influenza A virus (HPAIV) strain A/H5N1 with unprecedented spread through much of Asia and parts of Europe in poultry remains a serious threat to human health. Passive immunization (transfer of protective immunoglobulins) offers an alternative and/or additional strategy to prevent and cure influenza. Here, we report that vir...
Article
Full-text available
BACKGROUND: The ectodomain of matrix protein 2 (M2e) of influenza A virus is a rationale target antigen candidate for the development of a universal vaccine against influenza as M2e undergoes little sequence variation amongst human influenza A strains. Vaccine-induced M2e-specific antibodies (Abs) have been shown to display significant cross-protec...
Article
Full-text available
The sublingual route has been used for many years to deliver drugs and small molecules to the bloodstream. Surprisingly, the potential of this route for delivering vaccines has received very little if any attention until recently. During the past few years, a number of laboratories have documented the efficacy of sublingual immunization for inducin...
Article
Full-text available
Research has yielded an abundance of vaccine candidates against mucosal infections, but only few mucosal vaccines have been registered for human use. Extensive research is being carried out to identify new and safe adjuvants for mucosal immunization, novel delivery systems, including live vectors and reporter molecules for tissue- and cell-specific...
Article
The mucosal immune system exhibits a high degree of anatomic compartmentalization related to the migratory patterns of lymphocytes activated at different mucosal sites. The selective localization of mucosal lymphocytes to specific tissues is governed by cellular "homing" and chemokine receptors in conjunction with tissue-specific addressins and epi...
Article
Full-text available
Sublingual (SL) immunization has been described as an effective novel way to induce mucosal immune responses in the respiratory and genital tracts. We examined the potential of SL immunization against Helicobacter pylori to stimulate immune responses in the gastrointestinal mucosa and protect against H. pylori infection. Mice received two SL immuni...
Article
A randomized, double-blind, controlled clinical trial was conducted to evaluate the efficacy and safety of CJ-50300, a newly developed cell culture-derived smallpox vaccine, and to determine its minimum effective dose. The overall rates of cutaneous "take" reaction and humoral and cellular immunogenicity in CJ-50300 vaccinees were 100% (123/123), 9...
Article
Full-text available
A vaccine against heterosexual transmission by human immunodeficiency virus (HIV) should generate cytotoxic and antibody responses in the female genital tract and in extra-genital organs. We report that sublingual immunization with HIV-1 gp41 and a reverse transcriptase polypeptide coupled to the cholera toxin B subunit (CTB) induced gp41-specific...
Article
Full-text available
Background: Pandemic influenza poses a serious threat to global health and the world economy. While vaccines are currently under development, passive immunization could offer an alternative strategy to prevent and treat influenza virus infection. Attempts to develop monoclonal antibodies (mAbs) have been made. However, passive immunization based o...
Article
Full-text available
Atypical Vibrio cholerae O1 strains - hybrid strains (strains that cannot be classified either as El Tor or classical biotype) and altered strains (El Tor biotype strains that produce classical cholera toxin) - are currently prevalent in Asia and Africa. A total of 74 hybrid and altered strains that harboured classical cholera toxin were investigat...
Article
Full-text available
Langerhans cells (LCs) are dendritic cells (DCs) localized in stratified epithelia, such as those overlaying skin, buccal mucosa, and vagina. The contribution of LCs to the promotion or control of immunity initiated at epithelial sites remains debated. We report in this paper that an immunogen comprising OVA linked to the B subunit of cholera toxin...
Article
Induction of peripheral immunological tolerance by mucosal administration of selected antigens (Ags) ('oral tolerance') is an attractive, yet medically little developed, approach to prevent or treat selected autoimmune or allergic disorders. A highly effective way to maximize oral tolerance induction for immunotherapeutic purposes is to administer...
Article
Full-text available
Currently, Vibrio cholerae O1 serogroup biotype El Tor strains producing classical type cholera toxin (altered strains or El Tor variants) are prevalent in Asia and in Mozambique. Mozambican strains collected in 2004 contained a tandem repeat of CTX prophage on the small chromosome and each CTX prophage harboured the classical rstR and classical ct...
Article
Full-text available
Analysis of the CTX prophage and RS1 element in hybrid and altered Vibrio cholera O1 strains showed two classifiable groups. Group I strains contain a tandem repeat of classical CTX prophage on the small chromosome. Strains in this group either contain no element(s) or an additional CTX prophage or RS1 element(s) on the large chromosome. Group II s...
Article
Typhoid fever remains a serious public health problem in developing countries, especially among young children. Recent studies showed more than 50% of typhoid cases are in children under 5 years old. Licensed vaccines, such as Salmonella enterica serovar Typhi capsular Vi, did not confer protection against typhoid fever for this age group. Vi conju...
Article
Full-text available
We have recently reported that the sublingual (s.l.) mucosa is an efficient site for inducing systemic and mucosal immune responses. In this study, the potential of s.l. immunization to induce remote Ab responses and CD8(+) cytotoxic responses in the female genital tract was examined in mice by using a nonreplicating Ag, OVA, and cholera toxin (CT)...
Article
Full-text available
Our previous studies demonstrated the potential of the sublingual (s.l.) route for delivering vaccines capable of inducing mucosal as well as systemic immune responses. Those findings prompted us to attempt to identify possible inductive mechanism of s.l. vaccination for immune responses. Within 2 h after s.l. administration with cholera toxin (CT)...
Article
Full-text available
Enteric infections kill approximately two million children under the age of 5 in developing countries and cause more than four billion disease episodes worldwide each year. In addition, these diseases affect the growth, cognitive function, and quality of life negatively. There is an urgent need for vaccines that induce effective and long-lasting in...
Article
Full-text available
Vibrio cholerae O1 isolates collected during cholera outbreaks occurring from late 2007 to early 2008 in northern Vietnam were revealed to represent an altered strain containing the RS1 element followed by a CTX prophage harboring El Tor type rstR and classical ctxB on the large chromosome.
Article
Full-text available
Mucosal administration of Ag conjugated to cholera toxin B subunit (CTB) can efficiently induce peripheral immunologic tolerance, so-called oral tolerance, associated with development of Foxp3(+)CD25(+)CD4(+) regulatory T (Treg) cells. Using an established sublingual tolerization regimen with Ag(OVA)/CTB conjugate, wherein CTB mediates Ag uptake an...
Article
Full-text available
The sublingual locus has recently received great attention as a delivery site for various immunotherapies, including those that induce allergen-specific tolerance, and for vaccines that generate protective immunity. To further understand the immune functions of the human sublingual mucosa, we characterized the distribution of various immunocytes th...
Article
Oral immunization with vaccines against intestinal infectious diseases has been extensively explored for several decades. Despite the immunologic and economic rationale behind oral immunization, only a few mucosal vaccines are available for the prevention of mucosal infections. Here, we summarize the current status of such vaccines, with a focus on...