Development of a Highly Specific Anti-drug Antibody Assay in Support of a Nanoparticle-based Therapeutic.

PEGylated biotherapeutics can elicit anti-PEG (polyethylene glycol) immune responses in patients treated with this category of drugs. While anti-PEG antibody assays for this class of biotherapeutics have become a common element of the clinical immunogenicity testing strategy, the overall antibody incidence induced by the nanoparticle (NP) delivery system (such as ACCURINS®) has not been fully studied to date. To support the immunogenicity assessment of one of Pfizer's NP-based therapeutics, consisting of gedatolisib (GEDA) encapsulated in ACCURINS® (GEDA-NP), we developed an anti-GEDA-NP antibody (ADA) assay on the MSD platform for the detection of GEDA-NP induced ADA in human serum.

Protection provided by a herpes simplex virus 2 (HSV-2) glycoprotein C and D subunit antigen vaccine against genital HSV-2 infection in HSV-1-seropositive guinea pigs.

A prophylactic vaccine for genital herpes disease remains an elusive goal. We report the results of two studies performed collaboratively in different laboratories that assessed immunogenicity and vaccine efficacy in herpes simplex virus 1 (HSV-1)-seropositive guinea pigs immunized and subsequently challenged intravaginally with HSV-2. In study 1, HSV-2 glycoproteins C (gC2) and D (gD2) were produced in baculovirus and administered intramuscularly as monovalent or bivalent vaccines with CpG and alum.

Genetic variation in the vitamin C transporter, SLC23A2, modifies the risk of HPV16-associated head and neck cancer.

Human papillomavirus (HPV) type 16 infection is an etiologic factor in a subset of head and neck squamous cell carcinomas (HNSCC). It is unknown if host genetic susceptibility modifies the HPV16-HNSCC association. DNA samples collected as part of a Boston area case-control study of HNSCC were genotyped for single-nucleotide polymorphisms (SNPs) from the National Cancer Institute's SNP500Cancer database.

Human papillomavirus-16 modifies the association between fruit consumption and head and neck squamous cell carcinoma.

Human papillomavirus-16 (HPV-16) is a risk factor for head and neck squamous cell carcinoma (HNSCC). HPV-positive cancers have distinct disease cofactors and improved survival following treatment. There is conflicting evidence of a protective association of fruit consumption with HNSCC.

Evolution of type-specific immunoassays to evaluate the functional immune response to Gardasil: a vaccine for human papillomavirus types 16, 18, 6 and 11.

Epidemiological studies and clinical trials of vaccines depend on the accurate measurement of antibodies within the polyclonal response to infection or vaccination. The assay currently used to measure the antibody response to vaccination with GARDASIL [Quadrivalent Human Papillomavirus (Types 6, 11, 16, 18) Recombinant Vaccine]--a quadrivalent vaccine used against human papillomavirus (HPV) types 6, 11, 16, and 18--is a competitive Luminex assay (cLIA) that uses multiplex technology to detect type-specific neutralizing antibodies against all four HPV types in a single serum sample. Here we describe how the cLIA was developed, as well as how the monoclonal antibodies (mAbs), used as competitors in the assay, were characterized.

Lack of association of alcohol and tobacco with HPV16-associated head and neck cancer.

Background: Human papillomavirus type 16 (HPV16) seropositivity and alcohol and tobacco use have been associated with risk of head and neck squamous cell carcinoma (HNSCC). However, it is less clear whether HPV16 influences HNSCC risk associated with alcohol and tobacco use.

Methods: Incident cases of HNSCC diagnosed between December 1999 and December 2003 were identified from nine medical facilities in Greater Boston, MA.

Antibodies from women immunized with Gardasil cross-neutralize HPV 45 pseudovirions.

Human papillomavirus (HPV) types 6, 11, 16 and 18 L1 virus-like particles (VLPs) have been used to generate the prophylactic quadrivalent vaccine, Gardasil. There is a high degree of L1 homology between HPV types and it is likely that there is a substantial degree of surface exposed viral epitope similarity. An investigation of vaccine-induced antibody binding and neutralization was undertaken focusing on A7 species members, HPV 18 and 45.

Human papillomavirus 16 and head and neck squamous cell carcinoma.

Evidence suggests that human papillomavirus (HPV)16 seropositivity reflects past HPV16 exposure and is associated with risk for head and neck squamous cell carcinoma (HNSCC). Our objectives were to test the hypothesis that HPV16 seropositivity is associated with risk for HNSCC, to correlate HPV16 seropositivity with HPV16 tumor DNA, and to correlate HPV16 seropositivity and HPV16 DNA with sexual history and patient survival. In a case-control study of approximately 1,000 individuals, we assessed serology to the HPV16 L1 protein and in cases only, assayed tumors for HPV16 DNA.

Immunogenicity and reactogenicity of a novel vaccine for human papillomavirus 16: a 2-year randomized controlled clinical trial.

Objective: To evaluate the immunogenicity, reactogenicity, and tolerability of a prototype human papillomavirus (HPV) 16 viruslike particle (VLP) vaccine directed against the L1 capsid protein.

Subjects And Methods: We enrolled healthy nonpregnant women aged 18 to 26 years into a 2-year, double-blind, dose-ranging multicenter trial (October 12, 1998, to September 30, 2001). Subjects were assigned to study groups to receive a 3-dose regimen (day 0, month 2, and month 6) of 1 of 4 vaccine doses: 10 microg, 20 microg, 40 microg, or 80 microg or placebo.

A phase I study to evaluate a human papillomavirus (HPV) type 18 L1 VLP vaccine.

Human papillomavirus (HPV) infection can cause genital warts and cervical cancer. HPV types 6 and 11 cause >90% of genital wart cases; HPV16 and 18 cause 70% of cervical cancers. A prophylactic HPV (types 6, 11, 16, 18) L1 virus-like particle (VLP) vaccine may substantially reduce the incidence of these lesions.

Dose-ranging studies of the safety and immunogenicity of human papillomavirus Type 11 and Type 16 virus-like particle candidate vaccines in young healthy women.

Two candidate vaccines to prevent infection with human papillomavirus (HPV) Types 11 and 16 were studied in similar double-blind, placebo-controlled, dose-escalation trials. L1 virus-like particle (VLP) vaccines were made from recombinant L1 capsid protein of HPV11 or HPV16. Participants received 10, 20, 50, or 100 microg of HPV11 L1 VLPs, 10, 40, or 80 microg of HPV16 L1 VLPs, or placebo at Months 0, 2, and 6.

Early assessment of the efficacy of a human papillomavirus type 16 L1 virus-like particle vaccine.

A post hoc analysis was performed using combined data from two Phase I tolerability/immunogenicity studies of monovalent human papillomavirus type 11 (HPV11) or HPV16 L1 virus-like particle (VLP) vaccines. The goal was to determine if the HPV16 L1 VLP vaccine protected against HPV16 infection. Vaccine or placebo was given at 0, 2 and 6 months.

Effect of vaccine delivery system on the induction of HPV16L1-specific humoral and cell-mediated immune responses in immunized rhesus macaques.

There have been numerous studies to assess the immunogenicity of candidate therapeutic and prophylactic vaccines for human papillomavirus (HPV), but few of them have directly compared different vaccines in an immunologically relevant animal system. In the present study, several vaccine delivery systems (VLPs, chimeric VLPs, plasmid DNA, and a replication incompetent adenoviral vector) expressing HPV16L1 were evaluated for their ability to induce HPV16L1 VLP-specific humoral immune responses, including neutralizing antibodies, and cell-mediated immune responses in rhesus macaques. Monkeys immunized with HPV16L1 VLPs mounted a potent humoral response with strongly neutralizing antibodies and a strong L1-specific Th2 response as measured by IL-4 production by CD4+ T cells.

Simultaneous quantitation of antibodies to neutralizing epitopes on virus-like particles for human papillomavirus types 6, 11, 16, and 18 by a multiplexed luminex assay.

Several different methods have been developed to quantitate neutralizing antibody responses to human papillomaviruses (HPVs), including in vivo neutralization assays, in vitro pseudoneutralization assays, competitive radioimmunoassays (cRIAs), and enzyme-linked immunosorbent assays. However, each of these techniques possesses one or more limitations that preclude testing large numbers of patient sera for use in natural history studies and large vaccine clinical trials. We describe here a new multiplexed assay, by using the Luminex Laboratory MultiAnalyte Profiling (LabMAP3) assay system, that can simultaneously quantitate neutralizing antibodies to human papillomavirus types 6, 11, 16, and 18 in 50 micro l of serum.

Priming of human papillomavirus type 11-specific humoral and cellular immune responses in college-aged women with a virus-like particle vaccine.

In this study, we evaluated the potency of a human papillomavirus (HPV) virus-like particle (VLP)-based vaccine at generating HPV type 11 (HPV-11)-specific cellular and humoral immune responses in seronegative women. The vaccine was administered by intramuscular immunizations at months 0, 2, and 6. A fourth immunization was administered to approximately half of the women at month 12.