Céline Nguefeu Nkenfou

Bio: Céline Nguefeu Nkenfou is an academic researcher from University of Yaoundé I. The author has contributed to research in topics: Population & Medicine. The author has an hindex of 13, co-authored 50 publications receiving 543 citations. Previous affiliations of Céline Nguefeu Nkenfou include University of Yaoundé & Novartis Institute for Tropical Diseases.

On a mouse monoclonal antibody that neutralizes all four dengue virus serotypes

Abstract: The flavivirus envelope glycoprotein (E) is responsible for viral attachment and entry by membrane fusion. Its ectodomain is the primary target of the humoral immune response. In particular, the C-terminal Ig-like domain III of E, which is exposed at the surface of the viral particle, forms an attractive antigen for raising protective monoclonal antibodies (mAb). 9F12, a mouse mAb raised against a dengue virus (DENV) serotype 2 recombinant domain III, cross-reacts with corresponding domains from the other three DENV serotypes and also with West Nile virus. mAb 9F12 binds with nanomolar affinity to a conserved epitope that maps to the viral surface comprising residues 305, 307, 310 and 330 of the E protein. mAb 9F12 neutralizes all four DENV serotypes in plaque reduction assays. We expressed a single-chain Fv from 9F12 that retains the binding activity of the parent mAb. Adsorption and fusion inhibition assays indicate that mAb 9F12 prevents early steps of viral entry. Its virus inhibition activity and broad cross-reactivity makes mAb 9F12 a suitable candidate for optimization and humanization into a therapeutic antibody to treat severe infections by dengue.

Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control.

Abstract: Monocytes and macrophages are target cells for dengue infection. Besides their potential role for virus replication, activated monocytes/macrophages produce cytokines that may be critical for dengue pathology. To study the in vivo role of monocytes and macrophages for virus replication, we depleted monocytes and macrophages in IFN-alphabetagammaR knockout mice with clodronate liposomes before dengue infection. Although less virus was first recovered in the draining LN in the absence of macrophages, monocyte/macrophage depletion eventually resulted in a ten-fold higher systemic viral titer. A massive infiltration of CD11b(+)CD11c(low)Ly6C(low) monocytes into infected organs was observed in parallel with increasing virus titers before viremia was controlled. Depletion of monocytes in the blood before or after local infection had no impact on virus titers, suggesting that monocytes are not required as "virus-shuttles". Our data provide evidence that systemic viremia is established independently of tissue macrophages present at the site of infection and blood monocytes. Instead, we demonstrate the importance of monocytes/macrophages for the control of dengue virus.

Intestinal Parasitic Infections in HIV Infected and Non-Infected Patients in a Low HIV Prevalence Region, West-Cameroon

Abstract: The magnitude of intestinal parasitic infection in acquired immunodeficiency syndrome patients requires careful consideration in the developing world where poor nutrition is associated with poor hygiene and several tropical diseases However, there have been very few studies addressing this issue in Cameroon This study was conducted to determine the prevalence of intestinal parasitosis in HIV/AIDS patients in Dschang -Cameroon Stool and blood specimens from HIV/AIDS patients and control group were screened respectively for intestinal parasites and for HIV antibodies Intestinal parasites were identified using direct microscopy, formalin-ether concentration and Ziehl Neelsen methods Out of 396 participants recruited among patients consulting at hospital, 42 (106%) were HIV positive, thirty of them treatment naive The overall prevalence of intestinal parasites was 1464% Out of 42 HIV/AIDS patients, 595% (25/42) were infected with intestinal parasites, while only 932% (33/354) of the HIV negative patients were infected with intestinal parasites The parasites detected in our study population included Crystosporidium parvum (253%), Entamoeba histolytica (752%), Entamoeba coli (404%), Giardia lamblia (025%), Trichuris trichura (025%), Strongyloides stercoralis (025%) and Taenia spp (025%) In the HIV infected group, Crystosporidium parvum (1904%), Entamoeba histolytica (1904%), Entamoeba coli (2142%), Giardia lamblia (238%), Strongyloides stercoralis (025%) and Taenia spp (025%) were found Crystosporidium parvum was found to be significantly higher in HIV/AIDS patients than in controls (P<005) Multivariate analysis showed that the HIV status and the quality of water were the major risk factors for intestinal parasitosis Routine examinations of stool samples for parasites would significantly benefit the HIV patients by contributing in reducing morbidity and improving the efficiency of antiretroviral treatment Even after the introduction of free anti-retroviral drugs, opportunistic intestinal infections are still a threat HIV patients should be screened routinely for intestinal parasites and treated for their overall well being

Global Assessment of Dengue Virus-Specific CD4+ T Cell Responses in Dengue-Endemic Areas

Abstract: Background: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4+T cell responses, we mapped HLA-DRB1 restricted DENV-specific CD4+ T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. Methods: HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay. CD4+ T cells purified by magnetic bead negative selection were stimulated with HLA-matched epitope pools in the presence of autologous antigen presenting cells (APCs), followed by pool deconvolution to identify specific epitopes. The epitopes identified in this study were combined with those previously identified in the DENV endemic region of Sri Lanka, to generate a “megapool” (MP) consisting of 180 peptides specifically designed to achieve balanced HLA and DENV serotype coverage. The DENV CD4MP180 was validated by Intracellular Cytokine Staining (ICS) assays. Results: We detected responses directed against a total of 431 epitopes, representing all four DENV serotypes, restricted by 15 different HLA-DRB1 alleles. The responses were associated with a similar pattern of protein immunodominance, overall higher magnitude of responses, as compared to what was observed previously in the Sri Lanka region. Based on these epitope mapping studies, we designed a DENV CD4 MP180 with higher and more consistent coverage, which allowed the detection of CD4+ T cell DENV responses ex vivo in various cohorts of DENV exposed donors worldwide, including donors from Nicaragua, Brazil, Singapore, Sri Lanka and and U.S. domestic flavivirus-naive subjects immunized with Tetravalent Dengue Live Attenuated Vaccine (TV005). This broad reactivity reflects that the 21 HLA-DRB1 alleles analyzed in this and previous studies account for more than 80% of alleles present with a phenotypic frequency ≥ 5% worldwide, corresponding to 92% phenotypic coverage of the general population (i.e., 92% of individuals express at least one of these alleles). Conclusion: The DENV CD4 MP180 can be utilized to measure ex vivo responses to DENV irrespective of geographical location.

Selective and cross-reactive SARS-CoV-2 T cell epitopes in unexposed humans.

Abstract: Many unknowns exist about human immune responses to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. SARS-CoV-2-reactive CD4+ T cells have been reported in unexposed individuals, suggesting preexisting cross-reactive T cell memory in 20 to 50% of people. However, the source of those T cells has been speculative. Using human blood samples derived before the SARS-CoV-2 virus was discovered in 2019, we mapped 142 T cell epitopes across the SARS-CoV-2 genome to facilitate precise interrogation of the SARS-CoV-2-specific CD4+ T cell repertoire. We demonstrate a range of preexisting memory CD4+ T cells that are cross-reactive with comparable affinity to SARS-CoV-2 and the common cold coronaviruses human coronavirus (HCoV)-OC43, HCoV-229E, HCoV-NL63, and HCoV-HKU1. Thus, variegated T cell memory to coronaviruses that cause the common cold may underlie at least some of the extensive heterogeneity observed in coronavirus disease 2019 (COVID-19) disease.

MicroRNAs: Target Recognition and Regulatory Functions

Abstract: MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.