Cervical cancers (CxCa) may arise due to persistent infection with one of 13 high-risk (hr) mucosal human papillomavirus (HPV) types. Although cervical (PAP) screening has greatly reduced the incidence of CxCa, screening is less effective to prevent cervical adenocarcinoma (AC) associated with HPV16, HPV18 and other genus Alpha species 7 types. Common cutaneous HPV types cause skin, palmo-plantar, or plane warts, a common nuisance in children and immunosuppressed patients and frequent cause of medical consultation. In addition, genus Beta HPV types are implicated in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. The three licensed HPV vaccines (2-, 4-, 9-valent) are based upon virus-like particles (VLP) self-assembled from L1 major capsid protein. Vaccinations induce a type-restricted protective immune response against mucosal HPV types causing 70-90% of all CxCa and 90% of genital warts (4-, 9-valent vaccines). However, neither vaccine protects against cutaneous HPV, nor the remaining hr types. Thus, cervical screening needs to be maintained even in vaccinated women, further burdening health care systems. A strategy to develop broad-spectrum HPV vaccines is based on the minor structural protein L2 that contains type-common epitopes that induce low-titer cross-neutralizing antibodies. L2 is immunologically subdominant in co-assembled L1+L2 VLP, but its immunogenicity is increased when type-common L2 epitopes (e.g. ‘RG1 of HPV16 L2) are inserted into surface loops of HPV L1-VLP. In this thesis work, chimeric VLP antigens were designed to specifically target hr Alpha 7 HPV associated with cervical AC (HPV18L1-45RG1), cutaneous types causing warts (HPV1L1-4RG1), or NMSC-associated Beta HPV (HPV5L1-17RG1, HPV16L1-17RG1, HPV16L1-5L2(aa53-72) and HPV18L1-5L2(aa53-72)). Antisera to chimeric VLP were evaluated by in vitro neutralization assays, for which also 12 novel Beta type pseudovirions (PsV) were designed, and in vivo using a mouse vaginal challenge model. While chimeric VLP displaying RG1 peptides induced cross-neutralization to several tested HPV types, chimeric VLP based upon HPV5L2 aa53-72 (a homolog of a cross-neutralization HPV16 epitope) did not, suggesting possible structural and/or antigenic differences between cutaneous and mucosal hr HPV capsids. In vivo, HPV18L1-45RG1 VLP immunization conferred protection against challenge with HPV18/45/39/68 but not HPV59 or 16. Antisera to HPV5L1-17RG1 VLP partially protected against PsV challenge with Beta HPV20/24/96, but not against HPV5/38/76, whereas antisera to HPV16L1-17RG1 VLP fully protected against challenge with HPV20/96/16, and partially against HPV5/24/38, but not against HPV76. Passive transfer of immune serum raised against HPV1L1-4RG1 VLP partially protected against HPV4. In summary, novel L1-RG1 VLP immunogens have been generated as broader-spectrum HPV vaccine candidates, to protect against hr mucosal HPV types associated with AC and cutaneous HPV causing warts or being linked to skin cancer development.