The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial

Wajja, Anne; Kizito, Dennison; Nassanga, Beatrice; Nalwoga, Angela; Kabagenyi, Joyce; Kimuda, Simon G.; Galiwango, Ronald; Mutonyi, Gertrude; Vermaak, Samantha; Satti, Iman; Verweij, Jaco J.; Tukahebwa, Edridah M.; Cose, Stephen; Levin, Jonathan; Kaleebu, Pontiano; Elliott, Alison M.; McShane, Helen

doi:10.1371/journal.pntd.0005440

Cited by 29 publications

(30 citation statements)

References 46 publications

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“…A stronger Th1 response after the 2 nd vaccination is similar to the lack of bias seen in a study that aimed to investigate the effect of Schistosoma mansoni infection on the TB vaccine, MVA85A candidate vaccine [20]. Investigations involving individuals vaccinated with HPV L1 VLPs have shown strong Th1 and Th2 response in vitro indicated by high levels of IFN-γ, IL-5 and IL-10, especially in individuals with strong antibody titers.…”

Section: Chronic S Mansoni Infection Has No Significant Effect On Cymentioning

confidence: 55%

“…Schistosomiasis, has been estimated to affect more than 250 million people with majority of cases occurring in Sub-Saharan Africa [18]. Several studies have shown that parasitic infections, especially schistosomiasis, impair long-term responses of certain vaccines such as BCG [19], TB [20], hepatitis B [21] and tetanus toxoid [22] that require a predominant Th1 response to be effective. During a chronic helminth infection, there is a characteristic induction of a Th2 response which down regulates Th1 responses.…”

Section: Introductionmentioning

confidence: 99%

“…These immune response is essential for host's survival against the toxic effects of the Schistosoma egg antigens [23][24][25]. [20,22].…”

Section: Introductionmentioning

confidence: 99%

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An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses

et al. 2019

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Background Schistosoma mansoni is one of the most common helminth infections affecting a large population of people in sub-Saharan Africa. This helminth infection is known to cause immunomodulation which has affected the efficacy of a number of vaccines. This study examined whether a chronic schistosoma infection has an effect on the immunogenicity of HPV vaccine which is currently administered to girls and women aged 9 to 24. Little is known about the immune responses of the HPV vaccine in individuals with chronic schistosomiasis. Methods This study was carried out at the Institute of Primate Research (IPR) and involved an Olive baboon model. The experimental animals were randomly placed into three groups (n = 3-4); Two groups were infected with S. mansoni cercaria, and allowed to reach chronic stage (week 12 onwards), at week 13 and 14 post-infection, one group was treated with 80mg/kg of praziquantel (PZQ). Sixty four weeks post schistosoma infection, all groups received 2 doses of the Cervarix HPV vaccine a month apart. Specific immune responses to the HPV and parasite specific antigens were evaluated. Results Animals with chronic S. mansoni infection elicited significantly reduced levels of HPV specific IgG antibodies 8 weeks after vaccination compared the PZQ treated and uninfected groups. There was no significant difference in cellular proliferation nor IL-4 and IFN-γ production in all groups.

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Section: Chronic S Mansoni Infection Has No Significant Effect On Cymentioning

confidence: 55%

Section: Introductionmentioning

confidence: 99%

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An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses

et al. 2019

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“…In mice, SM has no impact on Mtb-specific cytokine production or antibody responses generated by DNA vaccination (33,34); however, it impairs Mtb-specific cytokine production following BCG vaccination and results in higher CFU of both BCG and Mtb (35,36). In humans, SM infection does not impair the generation of Mtb-specific T and B cells by the TB candidate vaccine MVA85A (37). In vitro studies of human PBMCs exposed to SM antigens have demonstrated skewing of Mtb-specific CD4 T cells from a TH1 to a TH2 response; however, human monocyte-derived macrophages exposed to the same antigens have produced contradictory results with one study showing enhanced control and another showing impaired control of Mtb replication in vitro (38,39).…”

Section: Introductionmentioning

confidence: 97%

CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses

et al. 2020

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Mycobacterium tuberculosis (Mtb) is a serious public health concern, infecting a quarter of the world and leading to 10 million cases of tuberculosis (TB) disease and 1. 5 million deaths annually. An effective type 1 CD4 T cell (TH1) immune response is necessary to control Mtb infection and defining factors that modulate Mtb-specific TH1 immunity is important to better define immune correlates of protection in Mtb infection. Helminths stimulate type 2 (TH2) immune responses, which antagonize TH1 cells. As such, we sought to evaluate whether co-infection with the parasitic helminth Schistosoma mansoni (SM) modifies CD4 T cell lineage profiles in a cohort of HIV-uninfected adults in Kisumu, Kenya. Individuals were categorized into six groups by Mtb and SM infection status: healthy controls (HC), latent Mtb infection (LTBI) and active tuberculosis (TB), with or without concomitant SM infection. We utilized flow cytometry to evaluate the TH1/TH2 functional and phenotypic lineage state of total CD4 T cells, as well as CD4 T cells specific for the Mtb antigens CFP-10 and ESAT-6. Total CD4 T cell lineage profiles were similar between SM + and SM − individuals in all Mtb infection groups. Furthermore, in both LTBI and TB groups, SM infection did not impair Mtb-specific TH1 cytokine production. In fact, SM + LTBI individuals had higher frequencies of IFNγ + Mtb-specific CD4 T cells than SM − LTBI individuals. Mtb-specific CD4 T cells were characterized by expression of both classical TH1 markers, CXCR3 and T-bet, and TH2 markers, CCR4, and GATA3. The expression of these markers was similar between SM + and SM − individuals with LTBI. However, SM + individuals with active TB had significantly higher frequencies of GATA3 + CCR4 + TH1 cytokine + Mtb-specific CD4 T cells, compared with SM − TB individuals. Together, these data indicate that Mtb-specific TH1 cytokine production capacity is maintained in SM-infected individuals, and that Mtb-specific TH1 cytokine + CD4 T cells can express both TH1 and TH2 markers. In high pathogen burden settings where co-infection is common and reoccurring, plasticity of antigen-specific CD4 T cell responses may be important in preserving Mtb-specific TH1 responses.

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“…However, as of November 2017, there were ongoing studies looking at aerosolized delivery of the vaccine (NCT01954563; NCT02532036). In 2017, studies were published that addressed the immunogenicity of the candidate tuberculosis vaccine MVA85A in Schistosomiasis‐ infected teenagers (Wajja 2017), and a further efficacy study in HIV‐exposed infants (Nemes 2018). …”

Section: Introductionmentioning

confidence: 99%

MVA85A vaccine to enhance BCG for preventing tuberculosis

Kashangura¹,

Jullien²,

Garner

et al. 2019

Cochrane Database of Systematic Reviews

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BackgroundTuberculosis causes more deaths than any other infectious disease globally. Bacillus Calmette‐Guérin (BCG) is the only available vaccine, but protection is incomplete and variable. The modified Vaccinia Ankara virus expressing antigen 85A (MVA85A) is a viral vector vaccine produced to prevent tuberculosis.ObjectivesTo assess and summarize the effects of the MVA85A vaccine boosting BCG in humans.Search methodsWe searched the Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL); MEDLINE (PubMed); Embase (Ovid); and four other databases. We searched the WHO ICTRP and ClinicalTrials.gov. All searches were run up to 10 May 2018.Selection criteriaWe evaluated randomized controlled trials of MVA85A vaccine given with BCG in people regardless of age or HIV status.Data collection and analysisTwo review authors independently assessed the eligibility and risk of bias of trials, and extracted and analyzed data. The primary outcome was active tuberculosis disease. We summarized dichotomous outcomes using risk ratios (RR) and risk differences (RD), with 95% confidence intervals (CI). Where appropriate, we combined data in meta‐analyses. Where meta‐analysis was inappropriate, we summarized results narratively.Main resultsThe search identified six studies relating to four Phase 2 randomized controlled trials enrolling 3838 participants. Funding was by government bodies, charities, and philanthropic donors. Five studies included infants, one of them infants born to HIV‐positive mothers. One study included adults living with HIV. All trials included authors from Oxford University who led the laboratory development of the vaccine. Participants received intradermal MVA85A after BCG in some studies, and before selective deferred BCG in HIV‐exposed infants.The largest trial in 2797 African children was well conducted with low risk of bias for most parameters. Risk of bias was uncertain for selective reporting because there were no precise case definition endpoints for active tuberculosis published prior to the trial analysis.MVA85A added to BCG compared to BCG alone probably has no effect on the risk of developing microbiologically confirmed tuberculosis (RR 0.97, 95% CI 0.58 to 1.62; 3439 participants, 2 trials; moderate‐certainty evidence), or the risk of starting on tuberculosis treatment (RR 1.10, 95% CI 0.92 to 1.33; 3687 participants, 3 trials; moderate‐certainty evidence). MVA85A probably has no effect on the risk of developing latent tuberculosis (RR 1.01, 95% CI 0.85 to 1.21; 3831 participants, 4 trials; moderate‐certainty evidence). Vaccinating people with MVA85A in addition to BCG did not cause life‐threatening serious adverse effects (RD 0.00, 95% CI –0.00 to 0.00; 3692 participants, 3 trials; high‐certainty evidence). Vaccination with MVA85A is probably associated with an increased risk of local skin adverse effects (3187 participants, 3 trials; moderate‐certainty evidence), but not systemic adverse effect related to vaccination (144 participants, 1 trial; low‐c...

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The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial

Cited by 29 publications

References 46 publications

An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses

An investigation into the role of chronic Schistosoma mansoni infection on Human Papillomavirus (HPV) vaccine induced protective responses

CD4 T Cells in Mycobacterium tuberculosis and Schistosoma mansoni Co-infected Individuals Maintain Functional TH1 Responses

MVA85A vaccine to enhance BCG for preventing tuberculosis

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