Active Immunization against
            <i>Pneumocystis carinii</i>
            with a Recombinant
            <i>P. carinii</i>
            Antigen

Wells, Jesse; Haidaris, Constantine G.; Wright, Terry W.; Gigliotti, Francis

doi:10.1128/iai.74.4.2446-2448.2006

Cited by 43 publications

(35 citation statements)

References 15 publications

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“…There is a high frequency of Pneumocystis-specific seroprevalence in immunocompetent adults (1,9), as well as in nonhuman primates (11,30), suggesting the persistence of serological memory or Pneumocystis-specific, long-lived plasma cells in response to natural Pneumocystis exposure. Antibodies to the Pneumocystis endoprotease kexin (KEX1) may be particularly important, because immune responses to Pneumocystis KEX1 have been associated with control of Pneumocystis infection in immunosuppressed murine models (62,63).…”

mentioning

confidence: 99%

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

Kling

Shipley²,

Patil³

et al. 2010

Infect Immun

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Pulmonary colonization by the opportunistic pathogen Pneumocystis jiroveci is common in HIV؉ subjects and has been associated with development of chronic obstructive pulmonary disease (COPD). Host and environmental factors associated with colonization susceptibility are undefined. Using a simian-human immunodeficiency virus (SHIV) model of HIV infection, the immunologic parameters associated with natural Pneumocystis jiroveci transmission were evaluated. SHIV-infected macaques were exposed to P. jiroveci by cohousing with immunosuppressed, P. jiroveci-colonized macaques in two independent experiments. Serial plasma and bronchoalveolar lavage (BAL) fluid samples were examined for changes in antibody titers to recombinant Pneumocystis-kexin protein (KEX1) and evidence of Pneumocystis colonization by nested PCR of BAL fluid. In experiment 1, 10 of 14 monkeys became Pneumocystis colonized (Pc ؉ ) by 8 weeks post-SHIV infection, while 4 animals remained Pneumocystis colonization negative (Pc ؊ ) throughout the study. In experiment 2, 11 of 17 animals became Pneumocystis colonized by 16 weeks post-SHIV infection, while 6 monkeys remained Pc ؊ . Baseline plasma KEX1-IgG titers were significantly higher in monkeys that remained Pc ؊ , compared to Pc ؉ monkeys, in experiments 1 (P ‫؍‬ 0.013) and 2 (P ‫؍‬ 0.022). Pc ؊ monkeys had greater percentages of Pneumocystis-specific memory B cells after SHIV infection compared to Pc ؉ monkeys (P ‫؍‬ 0.037). After SHIV infection, Pc ؉ monkeys developed progressive obstructive pulmonary disease, whereas Pc ؊ monkeys maintained normal lung function throughout the study. These results demonstrate a correlation between the KEX1 humoral response and the prevention of Pneumocystis colonization and obstructive lung disease in the SHIV model. In addition, these results indicate that an effective Pneumocystis-specific memory B-cell response is maintained despite progressive loss of CD4 ؉ T cells during SHIV infection.

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mentioning

confidence: 99%

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

Kling

Shipley²,

Patil³

et al. 2010

Infect Immun

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“…Circulating CD4 ϩ T cells were reduced from 13 to 18% to 0 to 1% of the total lymphocyte population sampled from the spleen. We then used an established mouse model of PcP that simulates natural infection by cohousing the susceptible, immunized mice with actively infected SCID mice (15). Pca1 immunization provided protection against subsequent infectious challenge (Table 1), with complete protection being defined as undetected organism burden by quantitative PCR (qPCR) (total lung organism burden below 10 4 , the lower limit of detection).…”

Section: Resultsmentioning

confidence: 99%

“…A number of potential vaccine candidates have been evaluated in animal models of PcP as well, but at best, they achieved only partial protection (15,(23)(24)(25)(26)(27). A recent publication also describes boosting naturally acquired antibody in Pneumocystisexposed animals with a fragment of kexin as a means to enhance immune response to Pneumocystis (28).…”

Section: Discussionmentioning

confidence: 99%

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Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii

et al. 2017

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Pneumocystis pneumonia (PcP) is a life-threatening infection that affects immunocompromised individuals. Nearly half of all PcP cases occur in those prescribed effective chemoprophylaxis, suggesting that additional preventive methods are needed. To this end, we have identified a unique mouse Pneumocystis surface protein, designated Pneumocystis cross-reactive antigen 1 (Pca1), as a potential vaccine candidate. Mice were immunized with a recombinant fusion protein containing Pca1. Subsequently, CD4 ϩ T cells were depleted, and the mice were exposed to Pneumocystis murina. Pca1 immunization completely protected nearly all mice, similar to immunization with whole Pneumocystis organisms. In contrast, all immunized negative-control mice developed PcP. Unexpectedly, Pca1 immunization generated cross-reactive antibody that recognized Pneumocystis jirovecii and Pneumocystis carinii. Potential orthologs of Pca1 have been identified in P. jirovecii. Such cross-reactivity is rare, and our findings suggest that Pca1 is a conserved antigen and potential vaccine target. The evaluation of Pca1-elicited antibodies in the prevention of PcP in humans deserves further investigation.

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“…In previous studies, a partial construct of A12 conferred some immunological pro-VOL. 8,2009 MEETING REVIEWS 451 tection against P. murina infection (139) and, by inference, could be an important target against P. jirovecii as well. Inflammatory signals in pathogenesis of pneumonia.…”

Section: Antibody Responses To Pneumocystis In Humansmentioning

confidence: 99%

Pneumocystis Workshop: 10th Anniversary Summary

Beck

Cushion

2009

Eukaryot Cell

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Active Immunization against Pneumocystis carinii with a Recombinant P. carinii Antigen

Cited by 43 publications

References 15 publications

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

Relationship of Pneumocystis jiroveci Humoral Immunity to Prevention of Colonization and Chronic Obstructive Pulmonary Disease in a Primate Model of HIV Infection

Immunization with Pneumocystis Cross-Reactive Antigen 1 (Pca1) Protects Mice against Pneumocystis Pneumonia and Generates Antibody to Pneumocystis jirovecii

Pneumocystis Workshop: 10th Anniversary Summary

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