Order Zurhausenvirales
Paul Pumpens, Peter Pushko, Philippe Le Mercier in Virus-Like Particles, 2022
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
William Bonnez in Guide to Genital HPV Diseases and Prevention, 2019
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
Satya Prakash Gupta in Cancer-Causing Viruses and Their Inhibitors, 2014
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.
The next generation of HCV vaccines: a focus on novel adjuvant development
Published in Expert Review of Vaccines, 2021
Kimia Kardani, Seyed Mehdi Sadat, Mona Kardani, Azam Bolhassani
It is crucial to develop effective therapeutic and preventive vaccines against HCV infection as well as DAA treatments. Several vaccine candidates have been developed but they were ineffective due to their low immunogenicity, insufficient antigen presentation, low stability, and complications in delivery. Therefore, scientists attempt to explore and develop novel adjuvants for overcoming some problems. Recently, for example, Sodium polyprenyl phosphate (antigen: the recombinant NS3/NS5B proteins), IMX313P (Oligomerization domain from the chicken complement inhibitor C4b-binding protein; antigen: DNA vaccine encoding a secreted and oligomerized form of E1/E2 proteins), and oligodeoxynucleotide of 39 bases (ODN39M; antigen: chimeric NS3EnvCo + E2 protein) as adjuvants could significantly induce antibody and Th1 immune responses against different HCV antigens in preclinical studies [22–2297]. For development of novel and potent adjuvants, further and better understanding about the innate and adaptive immune responses is required. The recent studies showed that the combination of various adjuvants can be helpful to boost the efficacy of HCV vaccines. Indeed, inducing several innate receptors seems to be more effective than activating a single receptor. Generally, some of the most successful combinations of adjuvants are the so-called AS01, AS02, AS03, AS04, MF59, and AF03 adjuvant systems. All these adjuvant combinations induce rapid activation of the innate immune response and increase antibody and T-cell responses. However, further studies are needed to determine the most effective adjuvants for HCV vaccine development in clinical trials.
Selection of adjuvants for vaccines targeting specific pathogens
Published in Expert Review of Vaccines, 2019
Indranil Sarkar, Ravendra Garg, Sylvia van Drunen Littel-van den Hurk
HPV effectively evades innate immunity by inhibiting the IFN receptor signaling pathways and activation of ISGs via the E6 and E7 proteins. HPV also downregulates TLR9 and does not induce any danger signal to alert the immune system [93]. This prolongs the duration of infection and delays the onset of adaptive immunity. Thus, an effective CMI is required to clear and control HPV infection. Effective vaccine-induced immunity against HPV should consist of CMI to the early proteins, E2 and E6, and neutralizing antibodies against the virus coat protein L1. Two currently approved HPV vaccines, Cervarix (a bivalent HPV 16/18 vaccine, GSK) and Gardasil (a quadrivalent HPV 6/11/16/18 vaccine, Merck) are highly protective against HPV 6, 11, 16 and 18 [94]. Both are LI VLPs; however, Cervarix is AS04-adjuvanted, while Gardasil is AAHS (amorphous aluminum hydroxyphosphate sulfate)-adjuvanted. VLPs strongly activate the stromal DCs in the injection site that migrate to the dLNs, or may directly bind to the surface of APCs or other immune cells and migrate to the LNs, where they prime naïve B cells [95]. According to a recent study in girls aged 9–14 years, two doses of Cervarix elicited superior HPV-16/18 antibody responses compared to two or three doses of Gardasil. The differences in immunogenicity between the two vaccines may be due to the different types of adjuvants used. AS04 enhances humoral immune responses and CMI by triggering local and transient cytokine responses that promote enhanced activation and presentation ability of APCs [96]. Significantly higher antibody titers are induced in mice immunized with HPV-16 L1 VLPs adsorbed onto AAHS as compared to VLPs adsorbed onto aluminum hydroxide along with induction of an improved L1-specific IFN-γ secreting T cell response [96].
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