Optimization Strategies for DNA Vaccines

Weeratna, Risini D.; McCluskie, Michael J.; Comanita, Lacrimiora; Wu, Tong; Davis, Heather L.

doi:10.1159/000053989

Cited by 9 publications

(5 citation statements)

References 85 publications

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“…In this study we clearly demonstrate that while a parenteral only approach will not induce a detectable mucosal immune response, parenteral immunization can prime for subsequent mucosal responses. We have also previously seen this with a plasmid DNA parenteral prime followed by a protein mucosal boost, whereby the combined strategy resulted in the induction of antigen-speci¢c IgA, despite none being detected with either route alone [27]. Thus there is an interaction between mucosal and systemic immune systems and these should not be regarded as distinct components of the immune system.…”

Section: Discussionmentioning

confidence: 90%

Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA

McCluskie¹

2002

FEMS Immunology and Medical Microbiology

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Synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants to protein antigens administered by parenteral or mucosal routes to BALB/c mice. To date, there have been no studies using combined parenteral/mucosal approaches with CpG DNA as adjuvant. In this study we evaluated different parenteral prime-mucosal boost and mucosal prime-parenteral boost strategies using hepatitis B surface antigen (HBsAg) alone or with different adjuvants: aluminum hydroxide (alum), cholera toxin (CT), CpG ODN. In addition, since CpG ODN has previously been shown to act synergistically with other adjuvants after parenteral or mucosal delivery, we also evaluated adjuvant combinations: alum+CpG ODN and CT+CpG ODN. The effects of adjuvant and administration strategy on systemic and mucosal humoral responses were measured, as well as cell-mediated immune responses (cytotoxic T lymphocyte activity). These results were compared to parenteral only or mucosal only strategies. Our findings demonstrate that parenteral immunization can prime for mucosal responses even when different lymph nodes were being targeted. HBsAg-specific immune responses (IgG in plasma, cytotoxic T lymphocytes) induced by parenteral prime could all be significantly enhanced by mucosal boosting and despite the fact that intramuscular immunization alone could not induce mucosal IgA, it could prime for a subsequent mucosal boost. In addition, the presence of adjuvant at time of boosting could influence the nature of subsequent immune responses (Th1 vs. Th2). Mice primed intranasally could have their systemic immune responses boosted with a parenteral administration and it was also possible to enhance mucosal responses induced by intranasal prime with an intramuscular boost.

show abstract

Section: Discussionmentioning

confidence: 90%

Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA

McCluskie¹

2002

FEMS Immunology and Medical Microbiology

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show abstract

“…In this study we clearly demonstrate that while a parenteral only approach will not induce a detectable mucosal immune response, parenteral immunization can prime for subsequent mucosal responses. We have also previously seen this with a plasmid DNA parenteral prime followed by a protein mucosal boost, whereby the combined strategy resulted in the induction of antigen‐specific IgA, despite none being detected with either route alone [27]. Thus there is an interaction between mucosal and systemic immune systems and these should not be regarded as distinct components of the immune system.…”

Section: Discussionmentioning

confidence: 91%

Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA

McCluskie¹,

Weeratna²,

Payette

et al. 2002

FEMS Immunology &Amp; Medical Microbiology

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Synthetic oligodeoxynucleotides (ODN) containing immunostimulatory CpG motifs (CpG ODN) are potent adjuvants to protein antigens administered by parenteral or mucosal routes to BALB/c mice. To date, there have been no studies using combined parenteral/ mucosal approaches with CpG DNA as adjuvant. In this study we evaluated different parenteral prime^mucosal boost and mucosal primep arenteral boost strategies using hepatitis B surface antigen (HBsAg) alone or with different adjuvants: aluminum hydroxide (alum), cholera toxin (CT), CpG ODN. In addition, since CpG ODN has previously been shown to act synergistically with other adjuvants after parenteral or mucosal delivery, we also evaluated adjuvant combinations: alum+CpG ODN and CT+CpG ODN. The effects of adjuvant and administration strategy on systemic and mucosal humoral responses were measured, as well as cell-mediated immune responses (cytotoxic T lymphocyte activity). These results were compared to parenteral only or mucosal only strategies. Our findings demonstrate that parenteral immunization can prime for mucosal responses even when different lymph nodes were being targeted. HBsAg-specific immune responses (IgG in plasma, cytotoxic T lymphocytes) induced by parenteral prime could all be significantly enhanced by mucosal boosting and despite the fact that intramuscular immunization alone could not induce mucosal IgA, it could prime for a subsequent mucosal boost. In addition, the presence of adjuvant at time of boosting could influence the nature of subsequent immune responses (Th1 vs. Th2). Mice primed intranasally could have their systemic immune responses boosted with a parenteral administration and it was also possible to enhance mucosal responses induced by intranasal prime with an intramuscular boost. ß

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“…It is now well recognized that DNA vaccines are poorly immunogenic in nonhuman primates and humans compared to mice (3,7,17,25,27).…”

mentioning

confidence: 99%

“…Immunostimulatory CpG oligodeoxynucleotides and coexpression of cytokines, e.g., granulocyte-macrophage colony-stimulating factor, interleukin-2 (IL-2), IL-10, IL-12, costimulatory molecules (B7), adhesion molecules (ICAM-1), and various delivery systems (cationic lipids, liposomes, microspheres, and lipid cochleate forms), have been used to increase the immunogenicity of DNA vaccines (17,23,27). Another approach is to use a heterologous boost with recombinant poxviruses (9,21) or with recombinant protein formulated in a suitable adjuvant (11).…”

mentioning

confidence: 99%

Induction of Plasmodium falciparum Transmission-Blocking Antibodies in Nonhuman Primates by a Combination of DNA and Protein Immunizations

Coban

Philipp²,

Purcell

et al. 2004

Infect Immun

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Malaria transmission-blocking vaccination can effectively reduce and/or eliminate transmission of parasites from the human host to the mosquito vector. The immunity achieved by inducing an antibody response to surface antigens of male and female gametes and parasite stages in the mosquito. Our laboratory has developed DNA vaccine constructs, based on Pfs25 (a Plasmodium falciparum surface protein of 25 kDa), that induce a transmission-blocking immune response in mice (C. A. Lobo, R. Dhar, and N. Kumar, Infect. Immun. 67:1688-1693, 1999). To evaluate the safety, immunogenicity, and efficacy of the Pfs25 DNA vaccine in nonhuman primates, we immunized rhesus macaques (Macaca mulatta) with a DNA vaccine plasmid encoding Pfs25 or a Pfg27-Pfs25 hybrid or with the plasmid (empty plasmid) alone. Immunization with four doses of these DNA vaccine constructs elicited antibody titers that were high but nonetheless unable to reduce the parasite's infectivity in membrane feeding assays. Further boosting of the antibody response with recombinant Pfs25 formulated in Montanide ISA-720 increased antibody titers (30-fold) and significantly blocked transmission of P. falciparum gametocytes to Anopheles mosquitoes (ϳ90% reduction in oocyst numbers in the midgut). Our data show that a DNA prime-protein boost regimen holds promise for achieving transmissionblocking immunity in areas where malaria is endemic and could be effective in eradicating malaria in isolated areas where the level of malaria endemicity is low.Plasmodium falciparum, one of the deadliest of the malariacausing species, continues to threaten humans, especially children and pregnant women, in many parts of the world (8). The available drugs and the vector control campaigns used to date have not had a significant impact on the transmission of malaria from humans to mosquitoes. When a female Anopheles mosquito bites an infected human, the male and female gametocytes (formed during the erythrocytic phase of the malaria life cycle) are taken up in the blood meal and rapidly undergo gametogenesis and fertilization. Oocysts and eventually infective sporozoites are formed, thus completing parasite development. It has been shown that the crucial link for malaria transmission, i.e., infectivity of male and female gametocytes, can be blocked in the mosquito vector by antibodies directed against sexual-stage-specific surface antigens when they are ingested along with the parasites in the blood meal (5, 12, 18). It is believed that transmission-blocking immunity will play a significant role in reducing the emergence of vaccine-resistant strains. Such strains could be selected by vaccines targeting erythrocytic asexual forms. Likewise, spread of drug resistance could be diminished by reducing overall malaria transmission (4).P. falciparum zygote-ookinete surface protein 25 (Pfs25) is one of the most promising candidates identified so far for the development of P. falciparum transmission-blocking vaccines. Pfs25 (a 25-kDa surface protein) is expressed at the onset of gametogenesis ...

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Optimization Strategies for DNA Vaccines

Cited by 9 publications

References 85 publications

Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA

Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA

Parenteral and mucosal prime-boost immunization strategies in mice with hepatitis B surface antigen and CpG DNA

Induction of Plasmodium falciparum Transmission-Blocking Antibodies in Nonhuman Primates by a Combination of DNA and Protein Immunizations

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