Vaccination with multimeric L2 fusion protein and L1 VLP or capsomeres to broaden protection against HPV infection

Abstract

Immunization with L1 as pentavalent capsomeres or virus-like particles (VLPs) generates high and long-lived titers of neutralizing antibodies and protection primarily against the human papillomavirus (HPV) type from which the vaccine was derived. Conversely, vaccination with L2 minor capsid protein derived from multiple HPV types induces lower titer, but more broadly neutralizing and protective antibody responses. We combined the advantages of each protective antigen by immunization with titrated doses of multi-type L2 with either L1 capsomeres or VLP. We observed no significant interference between the L1 and L2 antibody response upon co-administration of L1 vaccines with multi-type L2 vaccines.

Figure 1. Influence of adjuvant upon L2-specific antibody titers

Sera from each mouse was collected 2 weeks after the third dose of the indicated vaccines was titrated in 2-fold dilutions from 1:50 and tested by ELISA using plates coated with L2 11-88×5. (CpG=1018 ISS)

Figure 2. Influence of adjuvant upon L2-specific neutralizing antibody titers

Sera from each mouse was collected 2 weeks after the third dose of the indicated vaccines was titrated in 2-fold dilutions from 1:50 and tested for in vitro neutralization of HPV16 (A), or HPV18 (B), or HPV45 (C) pseudovirions.

Figure 3. Influence of adjuvant upon L2-specific neutralizing antibody titers four months after vaccination

Sera from each mouse was collected four months after the third dose of the indicated vaccines was titrated in 2-fold dilutions from 1:50 and tested for in vitro neutralization of HPV16 (A) or HPV45 (B) or HPV58 (C) pseudovirions.

Figure 4. L1 VLP and L2-specific antibody titers

Sera from each mouse was collected 2 weeks after the third dose of the indicated vaccine antigens in alum+MPL was titrated in 2-fold dilutions from 1:50 and tested by ELISA using plates coated with L2 11-88×5 (A), or HPV16 L1 VLP (B).

Figure 5. Influence of combining L2 11-88×5 with L1-based HPV vaccines upon neutralizing antibody titers

Sera from each mouse was collected two weeks after the third dose of the indicated vaccine antigens in alum+MPL was titrated in 2-fold dilutions from 1:50 and tested for in vitro neutralization of HPV16 (A), HPV18 (B), HPV35 (C), HPV45 (D), or HPV58 (E) pseudovirions.

Figure 6. Influence of combining L2 11-88×5 with L1-based HPV vaccines upon neutralizing antibody titers at four months after vaccination

Sera from each mouse was collected four months after the third dose of the indicated vaccine antigens in alum+MPL was titrated in 2-fold dilutions and tested for in vitro neutralization of HPV16 (A) or HPV45 (B) or HPV58 (C) pseudovirions.