A Phase 1 Study of a Recombinant Viruslike Particle Vaccine against Human Papillomavirus Type 11 in Healthy Adult Volunteers

Evans, Thomas G.; Bonnez, William; Rose, Robert C.; Koenig, Scott; Demeter, Lisa M.; Suzich, JoAnn; O'Brien, Diane; Campbell, M. H.; White, Wendy I.; Balsley, James; Reichman, Richard C.

doi:10.1086/320190

Cited by 170 publications

(82 citation statements)

References 50 publications

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“…Type I IFNs are produced by most, if not all cells, in response to virus infection (25) and are an essential link between innate and adaptive immunity (11,26). Therefore, we thought that these molecules might be involved in the adjuvant effect of BVs.…”

Section: Ifn-␣␤ Mediates the Adjuvant Property Of Bvsmentioning

confidence: 99%

Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

Hervás-Stubbs

Rueda

López

et al. 2007

The Journal of Immunology

155

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Baculoviruses (BVs) are dsDNA viruses that are pathogenic for insects. They have been used worldwide as selective bioinsecticides and for producing recombinant proteins in insect cells. Surprisingly, despite their widespread use in research and industry and their dissemination in the environment, the potential effects of these insect viruses on the immune responses of mammals remain totally unknown. We show in this study that BVs have strong adjuvant properties in mice, promoting potent humoral and CD8+ T cell adaptive responses against coadministered Ag. BVs also induce the in vivo maturation of dendritic cells and the production of inflammatory cytokines. We demonstrate that BVs play a major role in the strong immunogenicity of virus-like particles produced in the BV-insect cell expression system. The presence of even small numbers of BVs among the recombinant proteins produced in the BV expression system may therefore strengthen the immunological properties of these proteins. This adjuvant behavior of BVs is mediated primarily by IFN-αβ, although mechanisms independent of type I IFN signaling are also involved. This study demonstrates that nonpathogenic insect viruses may have a strong effect on the mammalian immune system.

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Section: Ifn-␣␤ Mediates the Adjuvant Property Of Bvsmentioning

confidence: 99%

Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

Hervás-Stubbs

Rueda

López

et al. 2007

The Journal of Immunology

155

View full text Add to dashboard Cite

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“…To meet medical needs imposed by HPV infection, several experimental vaccines have been developed and are currently in human clinical trials (Brown et al, 2001;Evans et al, 2001;Harro et al, 2001), and one has been shown to be effective in preventing persistent viral infection (Koutsky et al, 2002). These vaccines are based on viruslike particles (VLPs), which assemble spontaneously when the papillomavirus major capsid protein, L1, is recombinantly expressed either alone or together with L2, the minor capsid protein (Hofmann et al, 1995;Kirnbauer et al, 1992Kirnbauer et al, , 1993Neeper et al, 1996;Rose et al, 1993;Volpers et al, 1994;Zhou et al, 1991).…”

mentioning

confidence: 99%

Human papillomavirus type 6 virus-like particles present overlapping yet distinct conformational epitopes

Wang

Cook

Lee

et al. 2003

Journal of General Virology

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The epitope for a human papillomavirus (HPV) type 6 conformation-dependent, neutralizing monoclonal antibody (mAb) was partially mapped using HPV L1 recombinant virus-like particles (VLPs). The mAb H6.J54 is cross-reactive with the closely related HPV types 6 and 11. By making HPV-6-like amino acid substitutions in the cottontail rabbit papillomavirus (CRPV) major capsid protein L1, we were able to transfer H6.J54 binding activity into a CRPV/HPV-6 hybrid L1 protein.Full binding activity was achieved with only nine amino acid changes and identified a region centred on the HPV-6 residues 49-54. This region has previously been shown to be a critical part of HPV-6 type-specific epitopes. Fine mapping of the region by scanning a series of alanine substitution mutations showed that in HPV-6 VLPs this type-common epitope overlaps HPV-6 type-specific epitopes.

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“…18 In humans, a double-blind, placebo-controlled trial of 72 volunteers (58 females and 14 males) showed that the HPV 16 VLP vaccine developed at the NCI is well tolerated and highly immunogenic, even without adjuvants. 21 In the majority of recipients serum antibody titers that were approximately 40-fold higher than those observed in the natural infection were achieved.…”

Section: Vaccines Against Hpvmentioning

confidence: 88%

Prospects for primary prevention of cervical cancer in developing countries

Franceschi¹,

Clifford²,

Plummer³

2003

Salud pública Méx

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ResumenLos tipos de virus de papiloma humano (VPH) que causan cáncer cervical son sexualmente transmisibles, pero existe muy poca evidencia sobre que la infección pueda ser evitada por cambios en las conductas sexuales de alto riesgo, tales como el uso del condón. En contraste, vacunas profilácticas en contra del VPH pueden llegar a tener una muy elevada eficacia en la prevención de cáncer cervical. En principio, la efectividad de la vacunación contra el VPH, como estrategia para el control de cáncer cervical, puede ser evaluada por monitoreo secular en las tendencias de incidencia de cáncer cervical o mediante la conducción de ensayos clínicos aleatorizados. El primer tipo de estudios no puede demostrar en forma convincente su efectividad, porque las tasas de incidencia y mortalidad por cáncer cervical son influenciadas fuertemente por tendencias seculares que son independientes de las medidas de intervención. Estudios de fase 3 de vacunas profilácticas contra el VPH están siendo desarrollados actualmente. Cada uno de los ensayos es muy costoso e involucran complejos tipos de diseño. Esto es importante, sin embargo, deben iniciarse, tan pronto como sea posible, ensayos más simples diseñados para demostrar la efectividad de una vacuna contra el VPH en condiciones de campo, como las que pueden existir en países en desarrollo, donde el peso de la mortalidad por cáncer cervical es muy alto. Cada ensayo clínico puede cuantificar una diferencia en la presentación de lesiones precursoras de cáncer (el real blanco de una vacuna contra el VPH) en un periodo de seguimiento prolongado (20 años, al menos). En este artículo se presenta brevemente el posible diseño de este tipo de estudios, considerando dos áreas: India meridional y Corea del Sur. Este artículo también está disponible en: http://www.insp.mx/salud/index.html Palabras clave: vacuna; ensayos clínicos; cáncer cervical; virus de papiloma humano; proyecciones AbstractThe HPV types that cause cervical cancer are sexually transmitted, but there is little evidence that infection can be avoided by behavioural changes, such as condom use. In contrast, prophylactic vaccines against HPV infection are likely to have high efficacy. In principle, the effectiveness of HPV vaccination as a strategy for cervical cancer control can be measured either by monitoring secular trends in cervical cancer incidence or by conducting randomized trials. The former approach is unlikely to provide convincing evidence of effectiveness, since cervical cancer rates are subject to strong secular trends that are independent of intervention measures. A few phase III trials of HPV prophylactic vaccines are now being started. Such trials are very expensive studies involving frequent and complicated investigations. It is important, however, to start as soon as possible simpler trials designed to demonstrate the effectiveness of HPV vaccine in field conditions, i.e. in developing or intermediate countries which suffer the major burden of mortality from cervical cancer. Such trials may capture a diff...

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A Phase 1 Study of a Recombinant Viruslike Particle Vaccine against Human Papillomavirus Type 11 in Healthy Adult Volunteers

Cited by 170 publications

References 50 publications

Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

Insect Baculoviruses Strongly Potentiate Adaptive Immune Responses by Inducing Type I IFN

Human papillomavirus type 6 virus-like particles present overlapping yet distinct conformational epitopes

Prospects for primary prevention of cervical cancer in developing countries

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