Characterization of Immune Responses Induced by Intramuscular Vaccination with DNA Vaccines Encoding Measles Virus Hemagglutinin and/or Fusion Proteins

Song, Man Ki; Vindurampulle, Christofer J.; Capozzo, Alejandra Victoria; Ulmer, Jeffrey B.; Polo, John M.; Pasetti, Marcela F.; Barry, Eileen M.; Levine, Myron M.

doi:10.1128/jvi.79.15.9854-9861.2005

Cited by 29 publications

(20 citation statements)

References 53 publications

(59 reference statements)

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“…Second, albeit the fusion Ag alone might be insufficient for protection, CMI can be enhanced if fusion is given along with the hemagglutinin Ag (17), and such responses may synergize the protective effect of neutralizing Abs. A single DNA construct encoding both hemagglutinin and fusion Ags has practical advantages over coadministration of two different plasmids (17).…”

Section: Dna Vaccines Encoding Measles Virus (Mv)mentioning

confidence: 99%

“…A modified plasmid replicon pSINCP that incorporates nonstructural protein gene sequences from a human DC tropic Sindbis-virus was engineered to contain MV hemagglutinin, or both the hemagglutinin and fusion genes, resulting in plasmids pMSIN-H (3) and pMSINH-FdU (17). These constructs were selected for two reasons.…”

Section: Dna Vaccines Encoding Measles Virus (Mv)mentioning

confidence: 99%

“…CCL-10) grown in DMEM supplemented with 10% FCS (Invitrogen Life Technologies) were transfected with Sindbis-based constructs using LipofectAMINE (Invitrogen Life Technologies) as previously described (17). Briefly, 2 g of plasmid DNA were added to 5 ϫ 10 5 cells/well in a 6-well tissue culture plate.…”

Section: Western Immunoblot and Densitometric Analysismentioning

confidence: 99%

“…Pursuing a more efficient DNA vaccine approach to tackle the neonatal immune system, we developed Sindbis virus-based DNA plasmids encoding the MV hemagglutinin (3) and both the MV hemagglutinin and fusion glycoproteins (3,17). A modified plasmid replicon pSINCP that incorporates nonstructural protein gene sequences from a human DC tropic Sindbis-virus was engineered to contain MV hemagglutinin, or both the hemagglutinin and fusion genes, resulting in plasmids pMSIN-H (3) and pMSINH-FdU (17).…”

Section: Dna Vaccines Encoding Measles Virus (Mv)mentioning

confidence: 99%

“…The Sindbis virus-derived replicon pSINCP (Chiron) was used as the backbone for the construction of DNA plasmids encoding full-length MV hemagglutinin (pMSIN-H), MV fusion without the 5Ј nontranslated region (pMSIN-FdU), both under the control of a subgenomic promoter (3,17), and MV hemagglutinin and fusion in a bicistronic construct (pMSINHFdU) containing two separate subgenomic promoters (17). Plasmids were purified using endo-free Qiagen columns as indicated by the manufacturer and dissolved in sterile PBS to a final concentration of 0.6 and 1 mg/ml for vaccination of neonatal and adult mice, respectively.…”

Section: Plasmid Constructsmentioning

confidence: 99%

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Neonatal Immunization with a Sindbis Virus-DNA Measles Vaccine Induces Adult-Like Neutralizing Antibodies and Cell-Mediated Immunity in the Presence of Maternal Antibodies

Capozzo

Ramírez

Polo

et al. 2006

The Journal of Immunology

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Infants younger than age 9 mo do not respond reliably to the live attenuated measles vaccine due the immaturity of their immune system and the presence of maternal Abs that interfere with successful immunization. We evaluated the immune responses elicited by Sindbis virus replicon-based DNA vaccines encoding measles virus (MV) hemagglutinin (H, pMSIN-H) or both hemagglutinin and fusion (F, pMSINH-FdU) glycoproteins in neonatal mice born to naive and measles-immune mothers. Despite the presence of high levels of maternal Abs, neonatal immunization with pMSIN-H induced long-lasting, high-avidity MV plaque reduction neutralization (PRN) Abs, mainly IgG2a, that also inhibited syncytium formation in CD150+ B95-8 cells. IgG secreting plasma cells were detected in spleen and bone marrow. Newborns vaccinated with pMSINH-FdU elicited PRN titers that surpassed the protective level (200 mIU/ml) but were short-lived, had low syncytium inhibition capacity, and lacked avidity maturation. This vaccine failed to induce significant PRN titers in the presence of placentally transferred Abs. Both pMSIN-H and pMSINH-FdU elicited strong Th1 type cell-mediated immunity, measured by T cell proliferation and IFN-γ production, that was unaffected by maternal Abs. Newborns responded to measles DNA vaccines with similar or even higher PRN titers and cell-mediated immunity than adult mice. This study is the first demonstration that a Sindbis virus-based measles DNA vaccine can elicit robust MV immunity in neonates bypassing maternal Abs. Such a vaccine could be followed by the current live attenuated MV vaccine in a heterologous prime-boost to protect against measles early in life.

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Section: Dna Vaccines Encoding Measles Virus (Mv)mentioning

confidence: 99%

Section: Dna Vaccines Encoding Measles Virus (Mv)mentioning

confidence: 99%

Section: Western Immunoblot and Densitometric Analysismentioning

confidence: 99%