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Order Zurhausenvirales
Published in Paul Pumpens, Peter Pushko, Philippe Le Mercier, Virus-Like Particles, 2022
Paul Pumpens, Peter Pushko, Philippe Le Mercier
Second, the bivalent Cervarix™, containing the HPV16 and HPV18 L1 VLPs produced in baculovirus-infected insect cells and adjuvanted with AS04, has also shown sustained efficacy for up to 4.5 years (Harper et al. 2006; Schiller et al. 2008). Szarewski (2012) summarized the Cervarix™ vaccination data and stressed the significant cross-protection against some HPV types not included in the vaccine, where protection against HPV45 was particularly important, as this HPV type was relatively more common in adenocarcinoma. Moreover, the vaccine’s antibody response profile suggested a long duration of immunity.
Prevention
Published in William Bonnez, Guide to Genital HPV Diseases and Prevention, 2019
William Bonnez, Darron R. Brown, Cynthia M. Rand
The Cervarix efficacy data available have an average follow-up of five years, and antibody titers, which decline after the third dose but start plateauing after 18 months are still steady at five years. GSK believes that the AS04 adjuvant produces a stronger and more durable antibody immune response than amorphous aluminum hydroxyphosphate sulfate, the adjuvant used in Gardasil. It is currently conducting a study comparing Gardasil and Cervarix head-to-head. It is not possible for now to answer the question of duration of protection, and whether and when a booster will be needed.
Landscape of Papillomavirus in Human Cancers
Published in Satya Prakash Gupta, Cancer-Causing Viruses and Their Inhibitors, 2014
Susri Ray Chaudhuri (Guha), Anirban Roy, Indranil Chatterjee, Rahul Roy Chowdhury, Snehasikta Swarnakar
HPV vaccines offer a promising approach to the prevention of HPV and associated diseases. However, they do not replace other prevention strategies such as regular cervical cancer screening using the Pap test because the vaccines will not prevent all HPV types. There are two licensed HPV L1 virus-like particle (VLP) prophylactic vaccines: Cervarix®, a bivalent HPV-16 and -18 vaccine from GlaxoSmithKline Biologicals, Rixensart, Belgium, and Gardasil®, a quadrivalent HPV-16, -18, -6, and < -11 vaccine from Merck and Co., Inc., West Point, PA. Both the vaccines have been shown in randomized control trials to be highly efficacious against HPV-16 and -18 mediated CIN 2 and 3 in 15- to 26-year olds under a three-shot immunization schedule (0, 1 or 2, and 6 months) (Kjaer et al. 2009; Paavonen et al. 2009). Additional trial endpoints were evaluated for the quadrivalent vaccine with high efficacy (> 96%) against HPV-6/-11/-16/-18 mediated VIN and external genital warts (Dillner et al. 2010). In 16- to 23-year-old heterosexual men, the quadrivalent vaccine has been shown to achieve more than 90% efficacy against HPV-6, -11, -16, and -18 mediated external genital warts and more than 73% efficacy against AIN in homosexual men. The vaccines do not contain thimerosal or mercury as a preservative. The quadrivalent vaccine uses alum and the bivalent vaccine uses AS04 (500 μg aluminum hydroxide, 50 μg 3-O-deacyl-4´-monophosphoryl lipid A) as adjuvants. Both the vaccines should be delivered through a series of three intramuscular injections over a six-month period. The second and third doses should be given one (bivalent) or two (quadrivalent) and six months, respectively, after the first dose. Syncope can occur after vaccination and has been observed among adolescents and young adults. To avoid serious injury related to syncopal episodes, vaccine providers should consider observing patients for 15 minutes after they are vaccinated.
Preclinical developments in the delivery of protein antigens for vaccination
Published in Expert Opinion on Drug Delivery, 2023
Dylan A. Hendy, Alex Haven, Eric M. Bachelder, Kristy M. Ainslie
Given the primarily Th2 skewed response of alum, there has been the development of additional adjuvants for subunit vaccines. One such adjuvant is AS04, which is an adjuvant system developed by GSK that includes alum as well as monophosphoryl lipid A (MPL), a toll-like receptor 4 (TLR4) agonist. AS04 is in the human papillomavirus vaccine (HPV) Cervarix, which is a vaccine that includes antigens for HPV 16 and 18 in self-assembled virus-like-particles (VLPs) [30]. VLPs are also a subunit vaccine and they mimic the geometry of virus without being the ability or machinery to replicate or cause disease, further they differ from a viral capsid, which would contain additional proteins [31]. In a direct comparison between vaccination with alum alone or alum + MPL, MPL showed much higher humoral responses as well as a higher frequency of memory B cells after vaccination [32]. Overall, AS04 provides a more balanced Th1/Th2 immune response when compared to aluminum containing adjuvants alone; however, Cervarix was pulled from the U.S. market in 2016 due to low market demand likely because the competing HPV vaccine Gardasil protects against more types of HPV.
Subunit-based mucosal vaccine delivery systems for pulmonary delivery - Are they feasible?
Published in Drug Development and Industrial Pharmacy, 2019
Nirmal Marasini, Lisa M. Kaminskas
Alum is the most common adjuvant used in subunit vaccine formulation. Alum enhances vaccine efficacy by forming an antigen depot at the administration site that provides sustained and persistence antigen release. It elicits a potent humoral immunity that is primarily Th2-mediated (IgG1, IL-4, IL-5, IL-13), but is unable to initiate Th1 and CTL-mediated immunity [46,48]. In contrast, AS04, which contains monophosphoryl lipid A adsorbed in alum, promotes Th1 and cell-mediated immunity by stimulating the production of IL-12 and IFN- γ [48]. Therefore, it is important to select the right adjuvant to tailor the required immune response (e.g. MHC-I or MHC-II; Th1 or Th2 type) for overall clinical success. Unfortunately, no mucosal adjuvants are licensed for human use in pulmonary vaccines. This necessitates the development of new mucosal adjuvants, especially for pulmonary administration. Particle-based delivery systems can enhance humoral and cellular immunity by several mechanisms, including (a) enhancing antigen uptake by APCs, (b) protecting antigens against degradation by enzymes and acidic pH, and (c) acting as an antigen depot. While very few studies have investigated the use of micro- or nanoparticle-based platforms to deliver subunit vaccines into the lungs, these are more common in the nasal administration space. The following section will therefore summarize the literature regarding the use of particle-based adjuvant systems to deliver subunit vaccines to the lung and nasal mucosa.
Post-hoc analysis from phase III trials of human papillomavirus vaccines: considerations on impact on non-vaccine types
Published in Expert Review of Vaccines, 2019
Martin Ryser, Valérie Berlaimont, Naveen Karkada, Attila Mihalyi, Rino Rappuoli, Robbert van der Most
Our analysis aims to contribute to a better understanding of the heterogeneous overall efficacy of AS04-HPV and qHPV vaccines that has been reported in several reviews [17–19]. While head-to-head comparisons are not available, we now show that the overall efficacy of AS04-HPV and qHPV is influenced by efficacy against lesions that do not contain vaccine types. In the HPV naïve populations, efficacy against CIN3 not related to HPV types included in the respective vaccines was 81.3% (95%CI: 34.7; 96.5) for AS04-HPV and −58.7% (95%CI: −180.5; 8.5) for qHPV. Additional comparisons to efficacies against persistent infections with non-vaccine types point to potential vaccine mode of action mechanisms beyond neutralizing antibodies. Several hypotheses are discussed that synthesize the current immunological state-of-the-art. AS04-HPV and qHPV are formulated with different adjuvants possibly leading to the induction of different immune responses that may influence progression and/or clearance non-vaccine type related HPV infections that are acquired later in life. However, our analysis is limited by its post-hoc nature and the non-availability of clinical trials that compare vaccine efficacy of AS04-HPV and qHPV in a head-to-head setting. Additional research is needed to confirm or refute our study results as well as the proposed hypotheses. We suggest more detailed analyses of CD4 T-cell quality and antibody functional profiles in AS04-HPV and qHPV vaccinated subjects that could be informative. Also, it will be important to conduct large scale typing of advanced CIN lesions in unvaccinated and vaccinated populations in a real-world setting to establish absolute trends of non-vaccine type related lesions.