Immune responses induced by lower airway mucosal immunisation with a human papillomavirus type 16 virus-like particle vaccine

Nardelli-Haefliger, Denise; Lurati, Floriana; Wirthner, D.; Spertini, François; Schiller, John T.; Lowy, Douglas R.; Ponci, Françoise; Grandi, P. De

doi:10.1016/j.vaccine.2005.02.019

Cited by 95 publications

(67 citation statements)

References 43 publications

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“…immunization have resulted in variable immune responses and require larger doses (28). Furthermore, licensed HPV L1 VLP vaccines require an adjuvant (either alum or MPL).…”

Section: Discussionmentioning

confidence: 99%

Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2

Alphs¹,

Gambhira²,

Karanam³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

138

143

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Persistent infection with the high-risk subset of genitotropic human papillomavirus (HPV) genotypes is a necessary cause of cervical cancer. Given the global burden of cervical cancer, a low-cost, broadly protective vaccine is needed. RG-1 is a crossneutralizing and protective monoclonal antibody that recognizes residues 17-36 of HPV16 minor capsid protein L2. Because this epitope is highly conserved in divergent HPV types, we determined whether vaccination with HPV16 L2 17-36 peptide is broadly protective. The peptide was administered to BALB/c mice three times at monthly intervals, either alone or in the context of a synthetic lipopeptide vaccine candidate (P25-P2C-HPV) produced by linkage of the HPV peptide with a broadly recognized T helper epitope (P25) and the Toll-like receptor-2 (TLR2) ligand dipalmitoyl-S-glyceryl cysteine (P2C). In contrast to vaccination with the L2 17-36 peptide or P25-P2C alone, a potent L2-specific antibody response was generated to the P25-P2C-HPV lipopeptide when delivered either s.c. or intranasally. Sera from mice vaccinated with the P25-P2C-HPV lipopeptide neutralized not only HPV16 pseudovirions but also other evolutionarily divergent oncogenic genital (HPV18, HPV45) and cutaneous (HPV5, BPV1) types. The L2-specific antibody response depended on MHC class II, CD40, and MyD88 signaling. Additionally, vaccination with the P25-P2C-HPV lipopeptide protected mice from homologous challenge with HPV16 pseudovirions at cutaneous and genital sites and heterologous challenge with HPV45 pseudovirions. If provided in the appropriate context, therefore, HPV16 L2 17-36 might be used in a totally synthetic cross-protective HPV vaccine. G enitotropic human papillomavirus (HPV) infections are considered the most common sexually transmitted infection in the United States (1). The major manifestations of anogenital HPV include genital warts (condyloma acuminatum) and anogenital intraepithelial neoplasia. If left untreated, a small fraction of persistent high-risk HPV infections progresses to cancer. The presence of HPV DNA has been reported in 99.7% of cervical carcinomas worldwide, indicating that HPV infection is a necessary cause of this cancer and that this disease can be prevented by prophylactic HPV vaccination (2).Approximately 35 of the Ͼ100 subtypes of HPV are specific for the anogenital epithelium and have varying potentials for malignant transformation (3). Of the 15 oncogenic genital HPV types, HPV16 is the most common, followed by HPV18 and HPV45 (contributing Ϸ50%, 20%, and 10%, respectively, of cervical cancer cases worldwide). Public health efforts have successfully reduced the incidence and mortality of cervical cancer with the implementation of cervical cytology screening programs. Women who do not undergo regular screening account for most of the patients with invasive cancers (4), and cervical cancer remains the second most common cause of cancer death in women worldwide and the most prevalent cancer in women of sub-Saharan Africa, Central America, south-central Asia, and Me...

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“…immunization have resulted in variable immune responses and require larger doses (28). Furthermore, licensed HPV L1 VLP vaccines require an adjuvant (either alum or MPL).…”

Section: Discussionmentioning

confidence: 99%

Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2

Alphs¹,

Gambhira²,

Karanam³

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

138

143

View full text Add to dashboard Cite

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“…With a few exceptions [18,20], these assays have not been directly compared. L1 VLP-based ELISA has been extensively used in studies of HPV epidemiology and vaccinology [6,19,[21][22][23][24]. Generally, ELISAs are a fast and highly reproducible method for quantifying humoral responses against specific viral antigens, but the quantitation is independent of neutralizing activity.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of systemic and mucosal anti-HPV16 and anti-HPV18 antibody responses from vaccinated women

Kemp¹,

Garcı́a-Piñeres²,

Falk³

et al. 2008

Vaccine

106

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Ideal methods to monitor HPV neutralizing antibodies induced by vaccination have not been established yet. Here, we evaluated systemic and cervical antibody levels induced by HPV16/18 AS04-adjuvanted vaccine (GlaxoSmithKline Biologicals) using a secreted alkaline phosphatase neutralization assay (SEAP) and ELISA. Serum and cervical secretions from 50 vaccinated women were used to assess 1) overall assay reproducibility, 2) inter-assay and inter-specimen correlation; 3) correlations between month 1 and month 12 titers. Strong correlations between SEAP-NA and ELISA were observed (serum anti-HPV16/18, ρ=0.91/0.85; cervix anti-HPV16/18, ρ=0.84/0.89). Systemic and cervical antibody measures also correlated well (ρ range: 0.64 -0.75); except at mid-cycle (ρ range: 0.28 -0.65). Correlations between antibody levels at one and twelve months following the start of vaccination were poor (ρ range: 0.16 -0.38). In conclusion, HPV16/18 VLP-based ELISA is a reliable and valid method to monitor anti-HPV16/18 neutralizing potential for the first year following vaccination; however, additional studies will be Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Conflict of Interest: Troy J. Kemp, no conflict; Alfonso García-Piñeres, no conflict; Roni T. Falk, no conflict; Sylviane Poncelet is employed by GSK Biologicals, the manufacturer of the vaccine used in this trial; Francis Dessy is employed by GSK Biologicals, the manufacturer of the vaccine used in this trial; Sandra L. Giannini is employed by GSK Biologicals, the manufacturer of the vaccine used in this trial; Ana Cecilia Rodriguez, no conflict; Carolina Porras, no conflict; Rolando Herrero, no conflict; Allan Hildesheim, no conflict; Ligia A. Pinto, no conflict. Merocel is a trademark of Medtronic Ophthalmics, a division of Medtronic Xomed, Inc., Jacksonville, FL, and Hemastix is a trademark of Bayer Corporation, Elkhart, IN. NIH Public Access Author ManuscriptVaccine. Author manuscript; available in PMC 2014 August 13.

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“…Intranasal immunization has been shown to be an efficient route for vaccination, eliciting both mucosal and systemic IgG and IgA responses (7,8,13,39). Although DCs and alveolar macrophages have been implicated in the transport of Ag from the lung-mucosa to draining lymph nodes (30,31,(40)(41)(42), little is known about the transport of Ag from the lung to spleen.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously shown that VLPs reach the lung and induce high systemic antibody (Ab) titers following intranasal immunization (8). Moreover, studies in mice (7) and humans (13) have shown that induction of potent Ab responses requires the VLPs to reach the lower airways, indicating that the large mucosal surface area of the lung is important for the interaction of the VLPs with the immune system. Antibody responses are usually not induced in the mucosa but rather within B-cell follicles (FO) of secondary lymphoid organs.…”

mentioning

confidence: 99%

Low-affinity B cells transport viral particles from the lung to the spleen to initiate antibody responses

Bessa¹,

Zabel

Link³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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The lung is an important entry site for pathogens; its exposure to antigens results in systemic as well as local IgA and IgG antibodies. Here we show that intranasal administration of virus-like particles (VLPs) results in splenic B-cell responses with strong local germinalcenter formation. Surprisingly, VLPs were not transported from the lung to the spleen in a free form but by B cells. The interaction between VLPs and B cells was initiated in the lung and occurred independently of complement receptor 2 and Fcγ receptors, but was dependent upon B-cell receptors. Thus, B cells passing through the lungs bind VLPs via their B-cell receptors and deliver them to local B cells within the splenic B-cell follicle. This process is fundamentally different from delivery of blood or lymph borne particulate antigens, which are transported into B cell follicles by binding to complement receptors on B cells.trafficking | vaccine

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Immune responses induced by lower airway mucosal immunisation with a human papillomavirus type 16 virus-like particle vaccine

Cited by 95 publications

References 43 publications

Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2

Protection against heterologous human papillomavirus challenge by a synthetic lipopeptide vaccine containing a broadly cross-neutralizing epitope of L2

Evaluation of systemic and mucosal anti-HPV16 and anti-HPV18 antibody responses from vaccinated women

Low-affinity B cells transport viral particles from the lung to the spleen to initiate antibody responses

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