An immune competent mouse model for the characterization of recombinant measles vaccines

Abstract

Today, immune compromised interferon-α-receptor deficient mice expressing hCD46 (IFNARCD46tg) are usually used for measles virus (MV) based vaccine characterization. However, for the development of MV-based recombinant vaccine candidates (rMV), an immune competent mouse model is desirable in order to induce and evaluate meaningful immune response. In this study, humoral and cellular immune response induced by rMV in immune competent mice expressing human MV receptor CD46 (hCD46tg) were compared with those induced in wild-type black/6, and IFNARCD46tg mice.

 

All three strains developed humoral and cellular response against MV, whereas only hCD46tg and IFNARCD46tg mice developed a humoral response against the transgene. Differences were observed in the magnitude of the response, where the IFNARCD46tg mice displayed the strongest immune responses, followed by the hCD46tg mice and the black/6 mice. Interestingly, hCD46tg and wt black/6 mice showed a predominant CD4⁺ T-cell response against MV-N, whereas IFNARCD46tg mice developed both, CD4⁺ and CD8⁺ T-cell response against MV-N. Analysis of the cytokine profile of MV-N specific CD4⁺ T-cells and transgene (SIVgag) specific CD8⁺ T-cells revealed qualitative differences of the T-cell responses; noticeably a significant reduction of the frequency of CD4⁺IL-2⁺ expressing cells in IFNARCD46tg mice as compared with hCD46tg or wt black/6 mice.

We show in this study significant quantitative and qualitative differences in immune responses between immune competent and immune-compromised mice. Our results therefore highlight the importance of the animal model and support the use of hCD46tg mice as mouse model for the characterization of the immunological profile induced by recombinant measles virus vaccine candidates.

Keywords: :

• measles virus
• CD46
• recombinant vaccine
• mouse model
• humoral immunity
• cellular immunity

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgment

We would like to thank Kaspar Scherler, Jorge Barcos, Orhan Ilter, and Amanda Brogli for excellent technical support and animal care; Angelique Lemckert and Katarina Radosevic for organizing the hCD46tg-A mice; Armando Zuniga and Marian Wiegand for producing rMVs. We achnowledge the NIH AIDS Reagent and Reference Program for HIVand SIV anitbodies and peptides. This work was funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under Contract No. HHSN266200600018C to HYN.