• IMMUNE NETWORK
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• v.3 no.2
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• pp.110-117
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• 2003

Background: The usefulness of DNA vaccine at priming step of heterologous prime-boost vaccination led to DNA vaccine closer to practical reality. DNA vaccine priming followed by recombinant viral vector boosting via systemic route induces optimal systemic immunity but no mucosal immunity. Mucosal vaccination of the reversed protocol (recombinant viral vector priming-DNA vaccine boosting), however, can induce both maximal mucosal and systemic immunity. Here, we tried to address the reason why the mucosal protocol of prime-boost vaccination differs from that of systemic vaccination. Methods: To address the importance of primary immunity induced at priming step, mice were primed with different doses of DNA vaccine or coadministration of DNA vaccine plus mucosal adjuvant, and immunity including serum IgG and mucosal IgA was then determined following boosting with recombinant viral vector. Next, to assess influence of humoral pre-existing immunity on boosting $CD8^+$ T cell-mediated immunity, $CD8^+$ T cell-mediated immunity in B cell-deficient (${\mu}K/O$) mice immunized with prime-boost regimens was evaluated by CTL assay and $IFN-{\gamma}$-producing cells. Results: Immunity primed with recombinant viral vector was effectively boosted with DNA vaccine even 60 days later. In particular, animals primed by increasing doses of DNA vaccine or incorporating an adjuvant at priming step and boosted by recombinant viral vector elicited comparable responses to recombinant viral vector primed-DNA vaccine boosted group. Humoral pre-existing immunity was also unlikely to interfere the boosting effect of $CD8^+$ T cell-mediated immunity by recombinant viral vector. Conclusion: This report provides the important point that optimally primed responses should be considered in mucosal immunization of heterologous prime-boost regimens for inducing the effective boosting at both mucosal and systemic sites.

• Clinical and Experimental Vaccine Research
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• v.11 no.2
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• pp.209-216
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• 2022

Purpose: This study was performed to investigate humoral immune response and adverse events upon the heterologous prime-boost with a single dose of the mRNA-1273 vaccine among fully CoronaVac-vaccinated, infection-naïve healthcare workers in Indonesia. Materials and Methods: One hundred twenty-five eligible healthcare workers were recruited from one hospital for this prospective cohort study. Blood collection was conducted twice, i.e., on 7 days before and 28 days after the booster vaccination. The titer of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies was quantified accordingly. The post-vaccination adverse event was recorded for both CoronaVac and mRNA-1273 vaccinations. Any breakthrough infection was monitored during the follow-up period. Wilcoxon matched-pairs signed rank test was used to test differences between groups. Results: A significant increase was observed in the titer of anti-SARS-CoV-2 RBD antibodies upon receiving the mRNA-1273 booster (geometric mean titers of 65.57 and 47,445 U/mL in pre-and post-booster, respectively), supporting the argument to use heterologous prime-boost vaccination to improve the protection against COVID-19 in a high-risk population. The mRNA1273 vaccine, however, caused a higher frequency of adverse events than the CoronaVac vaccine. Nonetheless, the adverse events were considered minor medical events and temporary as all subjects were not hospitalized and fully recovered. Of note, no breakthrough infection was observed during the follow-up to 12 weeks post-booster. Conclusion: The heterologous prime-boost vaccination of healthcare workers with a single dose of the mRNA-1273 vaccine generated a significant elevation in humoral immune response towards RBD of SARS-CoV-2 and was associated with a higher frequency, but minor and transient, adverse events.

• IMMUNE NETWORK
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• v.5 no.2
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• pp.89-98
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• 2005

Background: DNA vaccination represents an anticipated approach for the control of numerous infectious diseases. Used alone, however, DNA vaccine is weak immunogen inferior to viral vectors. In recent, heterologous prime-boost vaccination leads DNA vaccines to practical reality. Methods: We assessed prime-boost immunization strategies with a DNA vaccine (minigene, $gB_{498-505}$ DNA) and recombinant vaccinia virus $(vvgB_{498-505})$ expressing epitope $gB_{498-505}$ (SSIEF ARL) of CD8+ T cells specific for glycoprotein B (gB) of herpes simplex virus (HSV). Animals were immunized primarily with $gB_{498-505}$ epitope-expressing DNA vaccine/recombinant vaccinia virus and boosted with alternative vaccine type expressing entire Ag. Results: In prime-boost protocols using vvgBw (recombinant vaccinia virus expressing entire Ag) and $vvgB_{498-505}$, CD8+ T cell-mediated immunity was induced maximally at both acute and memory stages if primed with vvgBw and boosted with $vvgB_{498-505}$ as evaluated by CTL activity, intracellular IFN-staining, and MHC class I tetramer staining. Similarly $gB_{498-505}$ DNA prime-gBw DNA (DNA vaccine expressing entire Ag) boost immunization elicited the strongest CD8+ T cell responses in protocols based on DNA vaccine. However, the level of CD8+ T cell-mediated immunity induced with prime-boost vaccination using DNA vaccine expressing epitope or entire Ag was inferior to those based on vvgBw and $vvgB_{498-505}$. Of particular interest CD8+ T cell-mediated immunity was optimally induced when $vvgB_{498-505}$ was used to prime and gB DNA was used as alternative boost. Especially CD7+ T cell responses induced by such protocol was longer lasted than other protocols. Conclusion: These facts direct to search for the effective strategy to induce optimal CD8+ T cell-mediated immunity against cancer and viral infection.

• Journal of Microbiology and Biotechnology
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• v.28 no.6
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• pp.1022-1029
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• 2018

Tuberculosis (TB) remains a serious health issue around the word. Adenovirus (Ad)-based vaccine and modified vaccinia virus Ankara (MVA)-based vaccine have emerged as two of the most promising immunization candidates over the past few years. However, the performance of the homologous and heterologous prime-boost immunization regimens of these two viral vector-based vaccines remains unclear. In the present study, we constructed recombinant Ad and MVA expressing an Ag85B-TB10.4 fusion protein (AdH4 and MVAH4) and evaluated the impact of their different immunization regimens on the humoral and cellular immune responses. We found that the viral vector-based vaccines could generate significantly higher levels of antigen-specific antibodies, $IFN-{\gamma}$-producing splenocytes, $CD69^+CD8^+$ T cells, and $IFN-{\gamma}$ secretion when compared with bacillus Calmette-$Gu{\acute{e}}rin$ (BCG) in a mouse model. AdH4-containing immunization regimens (AdH4-AdH4, AdH4-MVAH4, and MVAH4-AdH4) induced significantly stronger antibody responses, much more $IFN-{\gamma}$-producing splenocytes and $CD69^+CD8^+$ T cells, and higher levels of $IFN-{\gamma}$ secretion when compared with the MVAH4-MVAH4 immunization regimen. The number of $IFN-{\gamma}$-producing splenocytes sensitive to $CD8^+$ T-cell restricted peptides of Ag85B (9-1p and 9-2p) and Th1-related cytokines ($IFN-{\gamma}$ and $TNF-{\alpha}$) in the AdH4-MVAH4 heterologous prime-boost regimen immunization group was significantly higher than that in the other viral vector-based vaccine- and BCG-immunized groups, respectively. These results indicate that an immunization regimen involving AdH4 may have a higher capacity to induce humoral and cellular immune responses against TB in mice than that by regimens containing BCG or MVAH4 alone, and the AdH4-MVAH4 prime-boost regimen may generate an ideal protective effect.

• Journal of Microbiology and Biotechnology
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• v.18 no.7
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• pp.1326-1334
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• 2008

The prime-boost vaccination with DNA vaccine and recombinant viral vector has emerged as an effective prophylactic strategy to control infectious diseases. Here, we compared the protective immunities induced by multiple alternating immunizations with DNA vaccine (pCIgB) and replication-incompetent adenovirus (Ad-gB) expressing glycoprotein gB of pseudorabies virus (PrV). The platform of pCIgB-prime and Ad-gB-boost induced the most effective immune responses and provided protection against virulent PrV infection. However, priming with pCIgB prior to vaccinating animals by the DNA vaccine-prime and Ad-boost protocol provided neither effective immune responses nor protection against PrV. Similarly, boosting with Ad-gB following immunization with DNA vaccine-prime and Ad-boost showed no significant responses. Moreover, whereas the administration of Ad-gB for primary immunization induced Th2-type-biased immunity, priming with pCIgB induced Th1-type-biased immunity, as judged by the production of PrV-specific IgG isotypes and cytokine IFN-$\gamma$. These results indicate that the order and injection frequency of vaccine vehicles used for heterologous prime-boost vaccination affect the magnitude and nature of the immunity. Therefore, our demonstration implies that the prime-boost protocol should be carefully considered and selected to induce the desired immune responses.

• Journal of Microbiology and Biotechnology
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• v.25 no.4
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• pp.526-536
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• 2015

Leptospirosis is a worldwide zoonotic disease caused by pathogenic Leptospira, a genus of which more than 250 serovars have been identified. Commercial bacterin vaccines are limited in that they lack both cross-protection against heterologous serovars and long-term protection. This study investigated in mice the immunogenicity of an anti-leptospirosis vaccine, using the outer membrane proteins LipL32 and Loa22 as antigens. The immunogenicity of this vaccine formulation was compared with those induced by vaccines based on LipL32 or Loa22 alone. A DNA-encapsulated chitosan nanoparticle was used for in vivo DNA delivery. Using a unique DNA plasmid expressing both lipL32 and loa22 for vaccination, higher antibody responses were induced than when combining plasmids harboring each gene separately. Therefore, this formulation was used to test the immunogenicity when administered by a heterologous prime (DNA)-boost (protein) immunization regimen. The specific antibody responses against LipL32 (total IgG and IgG1) and Loa22 (IgG1) were higher in mice receiving two antigens in combination than in those vaccinated with a single antigen alone. Although no significant difference in splenic CD4⁺ T cell proliferation was observed among all groups of vaccinated mice, splenocytes from mice vaccinated with two antigens exhibited higher interferon-γ and IL-2 production than when using single antigens alone upon in vitro restimulation. Taken together, the immunogenicity induced by LipL32 and Loa22 antigens in a heterologous primeboost immunization regimen using chitosan as a DNA delivery system induces higher immune response, and may be useful for developing a better vaccine for leptospirosis.

• Proceedings of the Microbiological Society of Korea Conference
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• 2000.10a
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• pp.78-82
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• 2000

The AIDS epidemic continues unabated in many part of the world. After near two decades, no vaccine is available to combat the spread of this deadly disease. Much of the HIV -1 vaccine effort during the past decade has focused on the viral envelope glycoprotein, largely because it is the only protein that can elicit neutralizing antibodies (Nabs). Eliciting broadly cross-reactive Nabs has been a primary goal. The intrinsic genetic diversity of the viral envelope, however, has been one of the major impediments in vaccine development. We have recently completed a comprehensive study examining whether it is possible to elicit broadly acting Nabs by immunizing monkeys with mixtures of envelope proteins from multiple HIV -1 isolates. We compared the humoral immune responses elicited by vaccination with either single or multiple envelope proteins and evaluated the importance of humoral and non-humoral immune response in protection against a challenge virus with a homologous or heterologous envelope protein. Our results show that (1) Nab is the correlate of sterilizing immunity, (2) Nabs against primary HIV -1 isolates can be elicited by the live vector-prime/protein boost approach, and (3) polyvalent envelope vaccines elicit broader Nab response than monovalent vaccines. Nonetheless, our findings clearly indicate that the increased breadth of Nab response is by and large limited to strains included in the vaccine mixture and does not extend to heterologous non-vaccine strains. Our study strongly demonstrates how difficult it may be to elicit broadly reactive Nabs using envelope proteins and sadly predicts a similar fate for many of the vaccine candidates currently being evaluated in clinical trials. We have started to evaluate other vaccine candidates (e.g. genetically modified envelope proteins) that might elicit broadly reactive Nabs. We are also exploring other vaccine strategies to elicit potent cytotoxic T lymphocyte responses. Preliminary results from some of these experiments will be discussed.