Development of human papillomavirus chimaeric L1/L2 candidate vaccines

McGrath, Marieta; Villiers, Gillian K. de; Shephard, Enid G.; Hitzeroth, Inga I.; Rybicki, Edward P.

doi:10.1007/s00705-013-1713-8

Cited by 18 publications

(22 citation statements)

References 54 publications

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“…The other chimaeric L1s did not form distinct particles, and elicited significantly weaker humoral immune responses for the same dose of protein. The L1:L2 [108][109][110][111][112][113][114][115][116][117][118][119][120] particle formation was in contrast to repeated previous expression of this and the other chimaeras in insect cells, where only loose aggregates of capsomers were formed for L1:L2 [108][109][110][111][112][113][114][115][116][117][118][119][120] [95,96].…”

Section: Papillomavirus Vaccinesmentioning

confidence: 90%

Plant-based vaccines against viruses

Rybicki

2014

Virology Journal

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Plant-made or "biofarmed" viral vaccines are some of the earliest products of the technology of plant molecular farming, and remain some of the brightest prospects for the success of this field. Proofs of principle and of efficacy exist for many candidate viral veterinary vaccines; the use of plant-made viral antigens and of monoclonal antibodies for therapy of animal and even human viral disease is also well established. This review explores some of the more prominent recent advances in the biofarming of viral vaccines and therapies, including the recent use of ZMapp for Ebolavirus infection, and explores some possible future applications of the technology.

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Section: Papillomavirus Vaccinesmentioning

confidence: 90%

Plant-based vaccines against viruses

Rybicki

2014

Virology Journal

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“…Indeed, L2 cleavage on its N‐terminus by a host‐derived furin protease exposes epitopes upon the VLP capsid surface, including a well‐defined epitope 17‐36 recognised by the cross‐neutralising antibody, RG‐1 . VLPs containing L1 and L2 are also being investigated as alternative vaccines along with co‐administration of L1VLPs and L2 protein.…”

Section: Prophylactic Vaccinesmentioning

confidence: 99%

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

McKee

Bergot

Leggatt

2015

Reviews in Medical Virology

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It has been more than 7 years since the commercial introduction of highly successful vaccines protecting against highrisk human papillomavirus (HPV) subtypes and the development of cervical cancer. From an immune standpoint, the dependence of cervical cancer on viral infection has meant that HPV proteins can be targeted as strong tumour antigens leading to clearance of the infection and the subsequent protection from cancer. Commercially available vaccines consisting of the L1 capsid protein assembled as virus-like particles (VLPs) induce neutralising antibodies that deny access of the virus to cervical epithelial cells. While greater than 90% efficacy has been demonstrated at the completion of large phase III trials in young women, vaccine developers are now addressing broader issues such as efficacy in boys, longevity of the protection and inducing cross-reactive antibody for oncogenic, non-vaccine HPV strains. For women with existing HPV infection, the prophylactic vaccines provide little protection, and consequently, the need for therapeutic vaccines will continue into the future. Therapeutic vaccines targeting HPVE6 and E7 proteins are actively being pursued with new adjuvants and delivery vectors, combined with an improved knowledge of the tumour microenvironment, showing great promise. This review will focus on recent progress in prophylactic and therapeutic vaccine development and implementation since the publication of end of study data from phase III clinical trials between 2010 and 2012. Copyright © 2015 John Wiley & Sons, Ltd. INTRODUCTIONTargeting cancers for immunotherapy is often complicated by a lack of immunogenic tumour peptides. Mutated or overexpressed self-antigens are frequently the targets and invoke a generally low affinity/avidity T and B cell response. In contrast, the tight association between infection with HPV and cervical cancer means that foreign viral proteins encoded by HPV can provide the basis of either prophylactic or therapeutic cancer vaccines [1,2]. The natural course of anogenital HPV infection results in overwhelming clearance of the virus in 98% of individuals with an immune component suggested by the increased risk of HPV-associated cancers in immune-compromised organ transplant recipients [3,4]. However, HPV genotype-specific antibodies against the viral capsid proteins (L1 and L2) are produced at only low levels in about half the patients, can take close to a year to develop after natural infection and associate with higher viral loads in the cervix [5]. Thus, natural antibody may reflect the non-lytic, localised, intracellular nature of the infection leading to poor immunogenicity for immunoglobulin production and a greater emphasis on T-cell immunity for viral clearance. In contrast, prior immunization with HPV capsid proteins in animal studies induces high titres of antibody that are protective against challenge infection. Early studies in dogs demonstrated that prior immunization with L1 capsid protein could protect beagles from mucosal challenge with canine oral ...

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“…Another strategy for presenting L2 epitopes to the immune system is the use of HPV L1 VLPs as a display scaffold [63,69,70]. The rationale for these studies is that multivalent display of L2 on HPV16 VLPs will enhance its immunogenicity without sacrificing a strong anti-HPV16 response.…”

Section: Strategies For Targeting Hpv L2mentioning

confidence: 99%

Second-generation prophylactic HPV vaccines: successes and challenges

Tyler

Tumban

Chackerian

2013

Expert Review of Vaccines

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The role of human papillomavirus (HPV) as the causative factor in cervical cancer has led to the development of the HPV vaccines Gardasil and Cervarix. These vaccines effectively protect against two HPV types associated with 70% of cervical cancer cases. Despite this success, researchers continue to develop second generation HPV vaccines to protect against more HPV types and allow increased uptake in developing countries. While a reformulated vaccine based on the current technology is currently in clinical trials, another strategy consists of targeting highly conserved epitopes in the minor capsid protein of HPV, L2. Vaccines targeting L2 induce broadly neutralizing antibodies, capable of blocking infection by a wide range of HPV types. Several vaccine designs have been developed to optimize the display of L2 epitopes to the immune system and to reduce the cost of manufacture and distribution. L2-based vaccines show considerable promise as a potential next-generation HPV vaccine.

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Development of human papillomavirus chimaeric L1/L2 candidate vaccines

Cited by 18 publications

References 54 publications

Plant-based vaccines against viruses

Plant-based vaccines against viruses

Recent progress in vaccination against human papillomavirus‐mediated cervical cancer

Second-generation prophylactic HPV vaccines: successes and challenges

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