Specific memory B cell response and participation of CD4⁺ central and effector memory T cells in mice immunized with liposome encapsulated recombinant NE protein based Hepatitis E vaccine candidate

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• 作者：Shruti P. Kulkarni^a ; Subrat Thanapati^a ; Vidya A. Arankalle^b ; ^{varankalle@yahoo.com" class="auth_mail" title="E-mail the corresponding author} ; Anuradha S. Tripathy^a ; ^{anuradhastripathy@hotmail.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：HEV ; Hepatitis E Virus ; rNEp ; recombinant neutralizing epitope protein ; PI ; post immunization ; VI ; vaccine immunized ; VI-5μgμ ; mice immunized with 5g rNEp+ adjuvant ; VI-1μgμ ; mice immunized with 1g rNEp+ adjuvant ; ASCs ; antibody secreting cells ; TCM ; T central memory ; TEM ; T effector memory
• 刊名：Vaccine
• 出版年：2016
• 出版时间：21 November 2016
• 年：2016
• 卷：34
• 期：48
• 页码：5895-5902
• 全文大小：1327 K

文摘

Liposome encapsulated neutralizing epitope protein of Hepatitis E virus (HEV), rNEp, our Hepatitis E vaccine candidate, was shown to be immunogenic and safe in pregnant and non-pregnant mice and yielded sterilizing immunity in rhesus monkeys.

Methods

The current study in Balb/c mice assessed the levels and persistence of anti-HEV IgG antibodies by ELISA, frequencies of B, memory B, T and memory T cells by flow cytometry and HEV-specific IgG secreting memory B cells by ELISPOT till 420 days post immunization (PI) with 5 μg rNEp encapsulated in liposome based adjuvant (2 doses, 4 weeks apart). Mice immunized with a lower dose (1 μg) were assessed only for anamnestic response post booster dose.

Results

Vaccine candidate immunized mice (5 μg dose) elicited strong anti-HEV IgG response that was estimated to persist for lifetime. At day 120 PI, frequency of memory B cells was higher in immunized mice than those receiving adjuvant alone. Anti-HEV IgG titers were lower in mice immunized with 1 μg dose. A booster dose yielded a heightened antibody response in mice with both high (>800 GMT, 5 μg) and low (⩽100 GMT, 1 μg) anti-HEV IgG titers. At day 6th post booster dose, HEV-specific antibody secreting plasma cells (ASCs) were detected in 100% and 50% of mice with high and low anti-HEV IgG titers, respectively, whereas the frequencies of CD4⁺ central and effector memory T cells were high in mice with high anti-HEV IgG titers only.

Conclusions

Taken together, the vaccine candidate effectively generates persistent and anamnestic antibody response, elicits participation of CD4⁺ memory T cells and triggers memory B cells to differentiate into ASCs upon boosting. This approach of assessing the immunogenicity of vaccine candidate could be useful to explore the longevity of HEV-specific memory response in future HEV vaccine trials in human.