African Drylands Institute for Sustainability
College of Agriculture and Veterinary Science
University of Nairobi
P.O. Box 29053 00625
Nairobi , Kenya
Email:adis@uonbi.ac.ke /csdes@uonbi.ac.ke
Tel: 254-020-2133086
Fax: 254-020-632121
The pasture week aimed to inaugurate pasture production demonstrations- land preparation and broadcasting of the grass seeds
Farmers learning to construct a semi-circular band, a micro-structure for rainwater harvesting and conservation in Wajir County
National Dialogue on Policy Frameworks for Climate Change Adaptation, Disaster Risk Reduction, and Rangeland Management and Governance in Kenya’s Rangelands
Dr Kiama Peter Wangai Publications | ||||
1 | 2008 | Alcohol Related Deaths Amongst Drivers, Passengers, Pedestrians Andcyclists In Nairobi Click to View Abstract Introduction | ||
2 | 2006 | Identification Of A Novel HLA B*57 Restricted Cytotoxic T-lymphocyte Epitope Within HIV-1 Rev. Makadzange AT, Gillespie G, Kimani J, Kiama P, Easterbrook P, Bwayo JJ, Rowland-Jones SL. AIDS. 2006 Feb 14;20(3):462-4. Click to View Abstract HLA-B5701 and its related allele B5703 have been shown to be strongly associated with slow HIV-1 disease progression. To elucidate the effect of these alleles fully on disease progression it is essential to identify key HIV-1 epitopes that are restricted by these alleles. Here we describe the identification of a novel HLA-B5701, B5703 restricted epitope within HIV-1 rev, which accounted for up to 25 and 40% of the total cytotoxic T-lymphocyte responses in two patients. | ||
3 | 2005 | Elevated T Cell Counts And RANTES Expression In The Genital Mucosa Of HIV-1-resistant Kenyan Commercial Sex Workers. Iqbal SM, Ball TB, Kimani J, Kiama P, Thottingal P, Embree JE, Fowke KR, Plummer FA.J Infect Dis. 2005 Sep 1;192(5):728-38. Epub 2005 Jul Click to View Abstract The initial site of exposure to human immunodeficiency virus (HIV)-1 during heterosexual transmission occurs in the genital tract. Although the majority of immunological studies have focused on the immune response to HIV-1 at the systemic level, our understanding of tissue-specific immunity is deficient. The goal of the present study was to characterize T cell populations found in the cervix of women shown to be resistant to infection by HIV-1. Levels of both systemic and cervical mucosal lymphocytes were compared between HIV-1-resistant, HIV-1-uninfected, and HIV-1-infected commercial sex workers (CSWs) as well as HIV-1-uninfected non-CSW control subjects at low risk for exposure. The HIV-1-resistant CSWs had increased cervical CD4+ and CD8+ T cell counts, compared with the HIV-1-uninfected CSWs; importantly, these increases were not reflected in the systemic lymphocyte compartment. There was a 2-fold increase in CD4+ T cell counts in the HIV-1-resistant CSWs, compared with both the HIV-1-infected and the HIV-1-uninfected CSWs. Expression of the HIV-1 coreceptors CCR5 and CXCR4 was also determined, and cytokine and beta chemokine levels in the genital mucosa were assessed. The HIV-1-resistant CSWs had a 10-fold increase in RANTES expression, compared with the HIV-1-uninfected CSWs. This is the first study to show elevated levels of beta chemokines and CD4+ T cells in the genital tracts of women who are exposed to HIV-1 and yet are uninfected. | ||
4 | 2004 | Elevation Of Immune Activation In Kenyan Women Is Associated With Alterations In Immune Function: Implications For Vaccine Development. Koesters SA, Matu L, Kiama P, Anzala O, Embree J, Plummer FA, Kimani J, Fowke KR.J Clin Immunol. 2004 Nov;24(6):702-9. Click to View Abstract The infectious burden leading to immune activation can vary between different populations and lead to various immune dysfunctions. We compared the effect of immune activation on apoptosis and T cell function in HIV uninfected individuals from Nairobi, Kenya (n=34), and Winnipeg, Canada (n=10). Women from Nairobi had a significantly greater number of CD8+ T cells expressing the activation markers CD38 and HLA DR. Kenyan women also had significantly higher levels of CTLA-4+ CD4 and CD8+ T cells, and reduced levels of CD28+ CD8+ cells. Levels of CD95+ CD4+ T cells were higher in Kenyan women and, correspondingly, showed higher levels of spontaneous apoptosis. Kenyan women also demonstrated hyper-responsiveness to T cell activation as assessed by interferon gamma production. This study demonstrates that in a population of Kenyan women with high levels of T cell activation, there were also elevated levels of T cell apoptotic death and hyper-responsiveness. These differences may influence the efficacy of immune responses to pathogens and must be considered when testing candidate vaccines. | ||
5 | 2003 | Quantitative Ex Vivo Analysis Of Functional Virus-specific CD8 T Lymphocytes In The Blood And Genital Tract Of HIV-infected Women. Kaul R, Thottingal P, Kimani J, Kiama P, Waigwa CW, Bwayo JJ, Plummer FA, Rowland-Jones SL.AIDS. 2003 May 23;17(8):1139-44. Click to View Abstract BACKGROUND: CD8 T lymphocytes are important in HIV-1 control and mediate virus-specific immunity in the blood and genital tract. The induction and monitoring of mucosal CD8 cell responses will be an important component of HIV-1 vaccine trials, but information regarding the frequency, phenotype and function of genital tract CD8 cell responses is lacking. METHODS: Simultaneous blood and cervical cytobrush samples were obtained from 16 HIV-1-infected Kenyan sex workers. Epitope-specific CD8 T lymphocyte frequencies in the blood and genital tract were analysed after short-term peptide incubation and intracellular cytokine staining for interferon-gamma (IFN gamma). RESULTS: Cervical sampling resulted in adequate cell numbers for analysis in 10/16 women. Background IFN gamma production was higher in CD3+/CD8+ lymphocytes from the genital tract than from blood (0.48% versus 0.1%; P < 0.01). Responses to staphylococcal enterotoxin B were detected in cervical CD8 lymphocytes from 10/10 women, at a similar frequency to blood (16.7% in cervix and 13.3% in blood; P = 0.4). HIV-1-specific responses were detected the cervix of 8/10 women, with a trend to higher response frequencies in the genital tract than blood (2.1% versus 0.8%; P = 0.09). Co-expression of integrin CD103 (alpha E beta 7), a mucosal marker, was used to confirm the mucosal origin of cervical responses. CONCLUSIONS: Cytobrush sampling and intracellular cytokine staining is well suited to the analysis of cervical CD8 cell responses. The frequency of functional virus-specific CD3+/CD8+ T cells is similar in the genital tract and blood of HIV-1-infected women. The role of genital tract CD8 cell responses in HIV-1 control warrants further investigation. | ||
6 | 2002 | Cross-clade HIV-1-specific Neutralizing IgA In Mucosal And Systemic Compartments Of HIV-1-exposed, Persistently Seronegative Subjects. Devito C, Hinkula J, Kaul R, Kimani J, Kiama P, Lopalco L, Barass C, Piconi S, Trabattoni D, Bwayo JJ, Plummer F, Cleric Click to View Abstract There is an urgent need for a universally effective HIV-1 vaccine, but whether a vaccine will be able to protect against HIV-1 of different clades is a significant concern. IgA from HIV-1-exposed, persistently seronegative (HEPS) subjects has been shown to neutralize HIV-1 and to block epithelial HIV-1 transcytosis, and it may target novel HIV-1 epitopes. We have tested the ability of plasma and mucosal IgA purified from HEPS subjects to neutralize HIV-1 primary isolates of different viral clades and phenotypes. IgA from two groups of HEPS subjects was tested: sex workers from Nairobi, Kenya, where clades A and D predominate, and the heterosexual partners of individuals infected by clade B virus. HIV-1-infected and low-risk uninfected individuals were included as controls. IgA purified from the blood, genital tract, and saliva of most HEPS sex workers demonstrated significant cross-clade HIV-1 neutralization, whereas a more clade-restricted pattern of neutralization was found in partners of clade B-infected individuals. IgA purified from HIV-1-infected individuals also mediated cross-clade neutralization, whereas IgA from uninfected controls lacked neutralizing activity. In conclusion, mucosal and plasma IgA from HEPS subjects neutralizes HIV-1 of different clades. This ability to induce HIV-1-specific systemic and mucosal IgA may be an important feature of an effective prophylactic HIV-1 vaccine. | ||
7 | 2002 | Gonococcal Cervicitis Is Associated With Reduced Systemic CD8+ T Cell Responses In Human Immunodeficiency Virus Type 1-infected And Exposed, Uninfected Sex Workers. Kaul R, Rowland-Jones SL, Gillespie G, Kimani J, Dong T, Kiama P, Simonsen JN, Bwayo JJ, M Click to View Abstract Neisseria gonorrhoeae cervicitis and human immunodeficiency virus (HIV) type 1 frequently coinfect core transmitter populations, such as female sex workers. Gonococcal cervicitis is associated with increased viral shedding and plasma viremia in HIV-1-infected women and increased HIV-1 susceptibility in uninfected women. We studied the influence of gonococcal cervicitis on CD8(+) interferon (IFN)-gamma responses to HIV-1 and cytomegalovirus (CMV) epitopes in HIV-1-infected and in highly-exposed, persistently seronegative (HEPS) female sex workers. In HIV-1-infected women, gonococcal cervicitis was associated with reduced IFN-gamma responses in bulk CD8(+) lymphocyte populations, and intracellular cytokine staining, combined with class I major histocompatibility complex (MHC)-peptide tetramer studies, demonstrated reduced IFN-gamma production by HIV-1 epitope-specific CD8(+) lymphocytes. In HEPS sex workers, cervicitis was associated with the transient loss of systemic HIV-1-specific CD8(+) responses and with reduced function of CMV-specific CD8(+) lymphocytes. Impaired function of virus-specific CD8(+) lymphocytes may partly explain the deleterious effects of gonococcal cervicitis on HIV-1 immune control and susceptibility. | ||
8 | 2002 | Cross-reactive Cytotoxic T Lymphocytes Against A HIV-1 P24 Epitope In Slow Progressors With B*57.Gillespie GM, Kaul R, Dong T, Yang HB, Rostron T, Bwayo JJ, Kiama P, Peto T, Plummer FA, McMichael AJ, Rowland-Jones SL.AIDS. 2002 May 3;16(7):961-72. Click to View Abstract OBJECTIVES: To determine whether CD8 T lymphocytes from HIV-1-infected patients expressing B*5701 and B*5703 show broad cross-reactivity against different variants of a conserved p24 epitope, which might account for the good prognosis of HIV-1-infected individuals with HLA-B*57. DESIGN: B*5701+ and B*5703+ were recruited from Nairobi, Kenya and from Oxford, UK. All patients had been HIV positive for at least 8 years and could be categorized as slow progressors. METHODS: CD8 cytotoxic T cell clones were generated from B*5701+ and B*5703+ donors and tested for their ability to recognize clade variants of an index p24 epitope in standard cytolytic assays. Cross-reactive responses in freshly isolated peripheral blood mononuclear cells (PBMC) were assessed by interferon-gamma (IFNgamma) production and tetramer binding. RESULTS: Broad cross-clade reactivity for both cytolysis and tetramer binding was observed in CD8 T cell clones from patients harbouring the index epitope sequence. Patterns of cross-reactivity were similar in freshly isolated PBMC but varied between individuals in terms of strength and breath of responses generated. One common variant induced an unusual response with tetramer binding but often failed to induce IFNgamma production, and another was a weak stimulator of both IFNgamma and cytolytic activity. CONCLUSION: B*5701+ and B5703+ donors demonstrate broad functional cross-reactivity to both common and rare variants of a dominant p24 epitope, which could be relevant to the association of B*57 alleles with slow progression to AIDS. | ||
9 | 2001 | Human Leucocyte Antigen Supertypes And Immune Susceptibility To HIV-1, Implications For Vaccine Design. MacDonald KS, Matukas L, Embree JE, Fowke K, Kimani J, Nagelkerke NJ, Oyugi J, Kiama P, Kaul R, Luscher MA, Rowland-Jones S, Ndinya-Achola J, Ngugi E, Click to View Abstract { T cell responses against HIV-1 have been identified in a number of exposed uninfected populations. We hypothesized that the ability to mount an effective T cell response is partly determined by the human leucocyte antigens (HLA) phenotype of the individual. We examined whether certain HLA supertypes were associated with differential HIV-1 susceptibility in sexually exposed adults and in the setting of mother to child HIV-1 transmission. By multivariate analysis, decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related class I HLA alleles (A2/6802 supertype) in sexually exposed adults (Hazard ratio=0.42, 95% confidence intervals (CI): 0.22-0.81 | ||
10 | 2001 | Functional HIV-1 Specific IgA Antibodies In HIV-1 Exposed, Persistently IgG Seronegative Female Sex Workers. Broliden K, Hinkula J, Devito C, Kiama P, Kimani J, Trabbatoni D, Bwayo JJ, Clerici M, Plummer F, Kaul R. Immunol Lett. 2001 Nov 1;79(1-2):29-36. Click to View Abstract Although HIV-specific cellular immune responses are found in a number of HIV highly-exposed, persistently seronegative (HEPS) cohorts, late seroconversion can occur despite pre-existing cytotoxic T lymphocytes (CTL), suggesting that a protective HIV vaccine may need to induce a broader range of HIV-specific immune responses. Low levels of HIV-specific IgA have been found in the genital tract and plasma of the majority of Nairobi HEPS sex workers and appeared to be independent of HIV-specific cellular responses. IgA purified from genital tract, saliva and plasma of most HEPS sex workers were able to neutralize infection of PBMC by a primary (NSI) clade B HIV isolate, as well as viral isolates from clades A and D, which predominate in Kenya. In addition, these IgA were able to inhibit transcytosis of infective HIV virions across a transwell model of the human mucosal epithelium in an HIV-specific manner. Preliminary work in other HEPS cohorts has suggested the recognition of different gp41 epitopes in HEPS and HIV-infected subjects. Although present at low levels, these IgA demonstrated cross-clade neutralizing activity and were able to inhibit HIV mucosal transcytosis, suggesting an important functional role in protection against HIV infection. | ||
11 | 2001 | New Insights Into HIV-1 Specific Cytotoxic T-lymphocyte Responses In Exposed, Persistently Seronegative Kenyan Sex Workers. Kaul R, Rowland-Jones SL, Kimani J, Fowke K, Dong T, Kiama P, Rutherford J, Njagi E, Mwangi F, Rostron T, Onyango J, Oyugi J, MacDo Click to View Abstract A clearer understanding of HIV-1 specific immune responses in highly-exposed, persistently seronegative (HEPS) subjects is important in developing models of HIV-1 protective immunity. HIV-1 specific cytotoxic T-lymphocytes (CTL) have been described in a cohort of HEPS Kenyan sex workers, and recent work has further elucidated these responses. CTL specific for HIV-1 Env were found in the blood of over half the sex workers meeting criteria for HIV resistance, and in some women recognized unmapped epitopes. The proportion of women with Env-specific CTL increased with the duration of uninfected HIV exposure, suggesting that these responses were acquired over time. CD8+ lymphocyte responses directed against predefined HIV-1 CTL epitopes from various HIV-1 genes were found in the blood and genital tract of >50% resistant sex workers, at a ten-fold lower frequency than in infected subjects. The epitope specificity of CD8+ responses differs between HEPS and HIV infected women, and in HEPS the maintenance of responses appears to be dependent on persistent HIV exposure. Several HIV-1 'resistant' sex workers have become HIV infected over the past 6 years, possibly related to waning of pre-existing HIV-specific CTL, and infection has often been associated with a switch in the epitope specificity of CD8+ responses. These findings suggest that vaccine-induced protective HIV immunity is a realistic goal, but that vaccine strategies of boosting or persistent antigen may be necessary for long-lived protection. | ||
12 | 2001 | CD8(+) Lymphocytes Respond To Different HIV Epitopes In Seronegative And Infected Subjects. Kaul R, Dong T, Plummer FA, Kimani J, Rostron T, Kiama P, Njagi E, Irungu E, Farah B, Oyugi J, Chakraborty R, MacDonald KS, Bwayo JJ, McMichael A, Rowland-Jones SL Click to View Abstract HIV-1-specific cytotoxic T-lymphocyte (CTL) responses have been detected at a low frequency in many HIV-1-exposed, persistently seronegative (HEPS) subjects. However, it is unclear how CTLs could protect against HIV acquisition in HEPS subjects, when high levels of circulating CTL fail to prevent disease progression in most seropositive subjects. To address this issue we studied CD8(+) lymphocyte responses to a panel of HIV-1 CTL epitopes in 91 HEPS and 87 HIV-1-infected Nairobi sex workers. HIV-specific responses in seropositive women focused strongly on epitopes rarely or never recognized in HEPS subjects, who targeted epitopes that were subdominant or unrecognized in infected women. These differences in epitope specificity were restricted by only those HLA class I alleles that are associated with a reduced risk of HIV-1 infection in this cohort. Late seroconversion in HEPS donors was associated with a switch in epitope specificity and/or immunodominance to those epitopes preferentially recognized by HIV-1-infected women. The likelihood of detecting HIV-1-specific responses in HEPS women increased with the duration of viral exposure, suggesting that HIV-1-specific CD8(+) responses are acquired over time. The association between differential recognition of distinct CTL epitopes and protection from HIV-1 infection may have significant implications for vaccine design. | ||
13 | 2001 | Late Seroconversion In HIV-resistant Nairobi Prostitutes Despite Pre-existing HIV-specific CD8+ Responses. Kaul R, Rowland-Jones SL, Kimani J, Dong T, Yang HB, Kiama P, Rostron T, Njagi E, Bwayo JJ, MacDonald KS, McMichael AJ, Plummer FA.J Clin Invest. 20 Click to View Abstract Resistance to HIV infection in a small group of Kenyan sex workers is associated with CD8+-lymphocyte responses to HIV cytotoxic T-lymphocyte (CTL) epitopes. Eleven prostitutes meeting criteria for HIV resistance seroconverted between 1996 and 1999. The occurrence and specificity of preexisting HIV-1 epitope-specific responses were examined using the IFN-gamma enzyme-linked immunospot assay, and any epitopes recognized were cloned and sequenced from the infecting viral isolate. Immunologic and behavioral variables were compared between late seroconverters and persistently uninfected sex worker controls. HIV-1 CTL epitope responses were present in four of six cases, 5-18 months before seroconversion, and their presence was confirmed by bulk CTL culture. A possible viral escape mutation was found in one of six epitopes. The key epidemiologic correlate of late seroconversion was a reduction in sex work over the preceding year. In persistently uninfected controls, a break from sex work was associated with a loss of HIV-specific CD8+ responses. Late seroconversion may occur in HIV-1-resistant sex workers despite preceding HIV-specific CD8+ responses. Seroconversion generally occurs in the absence of detectable CTL escape mutations and may relate to the waning of HIV-specific CD8+ responses due to reduced antigenic exposure. | ||
14 | 2000 | Mucosal And Plasma IgA From HIV-1-exposed Uninfected Individuals Inhibit HIV-1 Transcytosis Across Human Epithelial Cells. Devito C, Broliden K, Kaul R, Svensson L, Johansen K, Kiama P, Kimani J, Lopalco L, Piconi S, Bwayo JJ, Plummer F, Clerici M, Hinkul Click to View Abstract HIV-1-specific IgA has been described in the genital tract and plasma of HIV-1 highly exposed, persistently seronegative (HEPS) individuals, and IgA from these sites has been shown to neutralize HIV-1. This study examines the ability of IgA isolated from HEPS individuals to inhibit transcytosis across a tight epithelial cell layer. A Transwell system was established to model HIV-1 infection across the human mucosal epithelium. The apical-basolateral transcytosis of primary HIV-1 isolates across this mucosal model was examined in the presence and the absence of IgA isolated from the genital tract, saliva, and plasma of HEPS individuals enrolled in both a sex worker cohort in Nairobi, Kenya, and a discordant couple cohort in Italy. In the absence of IgA, HIV-1 primary isolates were actively transported across the epithelial membrane and were released on the opposite side of the barrier. These transcytosed HIV-1 particles retained their ability to infect human mononuclear cells. However, IgA purified from the mucosa and plasma of HEPS individuals was able to inhibit HIV-1 transcytosis. Inhibition was seen in three of six cervicovaginal fluid samples, five of 10 saliva samples, and three of six plasma samples against at least one of the two primary HIV-1 isolates tested. IgA from low risk, healthy control subjects had no inhibitory effect on HIV-1 transcytosis. The ability of mucosal and plasma IgA to inhibit HIV-1 transcytosis across the mucosal epithelium may represent an important mechanism for protection against the sexual acquisition of HIV-1 infection in HEPS individuals. | ||
15 | 2000 | HIV-1-specific Mucosal CD8+ Lymphocyte Responses In The Cervix Of HIV-1-resistant Prostitutes In Nairobi.Kaul R, Plummer FA, Kimani J, Dong T, Kiama P, Rostron T, Njagi E, MacDonald KS, Bwayo JJ, McMichael AJ, Rowland-Jones SL. J Immunol. 2000 Feb 1;164(3 Click to View Abstract Understanding how individuals with a high degree of HIV exposure avoid persistent infection is paramount to HIV vaccine design. Evidence suggests that mucosal immunity, particularly virus-specific CTL, could be critically important in protection against sexually acquired HIV infection. Therefore, we have looked for the presence of HIV-specific CD8+ T cells in cervical mononuclear cells from a subgroup of highly HIV-exposed but persistently seronegative female sex workers in Nairobi. An enzyme-linked immunospot assay was used to measure IFN-gamma release in response to known class I HLA-restricted CTL epitope peptides using effector cells from the blood and cervix of HIV-1-resistant and -infected sex workers and from lower-risk uninfected controls. Eleven of 16 resistant sex workers had HIV-specific CD8+ T cells in the cervix, and a similar number had detectable responses in blood. Where both blood and cervical responses were detected in the same individual, the specificity of the responses was similar. Neither cervical nor blood responses were detected in lower-risk control donors. HIV-specific CD8+ T cell frequencies in the cervix of HIV-resistant sex workers were slightly higher than in blood, while in HIV-infected donor cervical response frequencies were markedly lower than blood, so that there was relative enrichment of cervical responses in HIV-resistant compared with HIV-infected donors. HIV-specific CD8+ T cell responses in the absence of detectable HIV infection in the genital mucosa of HIV-1-resistant sex workers may be playing an important part in protective immunity against heterosexual HIV-1 transmission. |
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