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Comparative Study
. 2010 Jun 17;28(28):4478-86.
doi: 10.1016/j.vaccine.2010.04.039. Epub 2010 Apr 29.

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

Subhashini Jagu  1 , Kihyuck Kwak, Robert L Garcea, Richard B S Roden
Affiliations
Comparative Study

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

Subhashini Jagu et al. Vaccine. .

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.

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Conflict of interest statement

Competing Interests: RBSR is a paid consultant of Merck & Co, Inc., and Knobbe Martens Olson & Bear LLC. SJ and RBSR have received unrestricted educational grant funding from GlaxoSmithKline. RBSR and SJ are co-inventors on L2 patents licensed to Shantha Biotechnics, Ltd., PaxVax, Inc. and Acambis, Inc. The terms of these arrangements are being managed by Johns Hopkins University in accordance with its conflict of interest policies.

Figures

Figure 1
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
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
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
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
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
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.
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