Attenuated<i>Salmonella enterica</i>Serovar Typhi and<i>Shigella flexneri</i>2a Strains Mucosally Deliver DNA Vaccines Encoding Measles Virus Hemagglutinin, Inducing Specific Immune Responses and Protection in Cotton Rats

Pasetti, Marcela F.; Barry, Eileen M.; Losonsky, Genevieve A.; Singh, Mahender; Medina‐Moreno, Sandra; Polo, John M.; Ulmer, Jeffrey B.; Robinson, Harriet L.; Sztein, Marcelo B.; Levine, Myron M.

doi:10.1128/jvi.77.9.5209-5217.2003

Cited by 65 publications

(39 citation statements)

References 55 publications

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“…Female BALB/c mice (8-10 wk old) were immunized i.m. with 100 g of pMSIN-H, pMSINH-FdU, or pSINCP suspended in PBS (50 l per hind leg) as previously described (3). All mice received a booster dose 14 or 28 days after the initial immunization.…”

Section: Mice and Immunizationsmentioning

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%

“…4 Ags have been pursued as promising measles vaccine candidates. Several studies have shown a degree of protective efficacy using a variety of DNA plasmids encoding MV hemagglutinin and fusion glycoproteins in cotton rats (3,4) and rhesus macaques (5)(6)(7).…”

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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: Mice and Immunizationsmentioning

confidence: 99%

Section: Dna Vaccines Encoding Measles Virus (Mv)mentioning

confidence: 99%

Section: Plasmid Constructsmentioning

confidence: 99%

mentioning

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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“…5 Mucosal administration of currently licensed measles vaccine is a component of the WHO measles morbidity reduction and elimination strategy 6 as well as heterologous prime-boost approaches to closing the window of susceptibility. 7 Aerosol administration has been determined to be safe and efficacious, but it has not been determined whether nasal, bronchial, or alveolar deposition is necessary. 8 Intranasal administration of live-attenuated influenza vaccine is licensed, but intranasal administration of live-attenuated measles vaccine has not been well studied.…”

Section: Introductionmentioning

confidence: 99%

A Clinical Study to Assess the Safety and Immunogenicity of Attenuated Measles Vaccine Administered Intranasally to Healthy Adults

Simon¹,

Pasetti²,

Viret³

et al. 2007

Human Vaccines

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Background. Despite the availability of a safe and effective vaccine for over four decades, measles remains one of the most common infectious disease killers of children in the world. Mucosal administration of currently licensed measles vaccine has been proposed to address issues of needle safety and improve vaccine uptake.Methods. Healthy adult volunteers were randomized to receive live-attenuated monovalent measles virus vaccine (Moraten Berna) via the standard subcutaneous (SQ) or the experimental intranasal (IN) route in a randomized, double-masked fashion. Safety, reactogenicity, immunogenicity, and shedding were assessed.Results. Safety, reactogenicity, and viral shedding were not significantly different in the two study groups. Immunogenicity was markedly lower in the group of volunteers that received vaccine via the IN route. Plaque reduction neutralization (PRN) geometric mean titers (GMT) were 125 (95% confidence interval [CI] 68-228) milli International Units per milliliter (mIU/mL) on day 28 in recipients of IN vaccine versus 645 (95% CI 468-889) mIU/mL in recipients of vaccine SQ; p<0.001 by Mann-Whitney Rank Sum. 50% of measles non-immune individuals mounted titers above the protective threshold of PRN 200 mIU/mL after IN administration versus 100% of volunteers who received the vaccine SQ.Conclusion. Intranasal administration of live-attenuated measles vaccine was safe and well tolerated, but failed to mount significant immune responses when compared to subcutaneous administration. It is possible that higher doses or smaller particle size are necessary for successful intranasal measles vaccination and boosting.

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Bacterial gene therapy strategies

Vassaux

Nitcheu

Jezzard

et al. 2005

The Journal of Pathology

117

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The ability of bacteria to mediate gene transfer has only recently been established and these observations have led to the utilization of various bacterial strains in gene therapy. The types of bacteria used include attenuated strains of Salmonella, Shigella, Listeria, and Yersinia, as well as non-pathogenic Escherichia coli. For some of these vectors, the mechanism of DNA transfer from the bacteria to the mammalian cell is not yet fully understood but their potential to deliver therapeutic molecules has been demonstrated in vitro and in vivo in experimental models. Therapeutic benefits have been observed in vaccination against infectious diseases, immunotherapy against cancer, and topical delivery of immunomodulatory cytokines in inflammatory bowel disease. In the case of attenuated Salmonella, used as a tumour-targeting vector, clinical trials in humans have demonstrated the proof of principle but they have also highlighted the need for the generation of strains with reduced toxicities and improved colonization properties. Altogether, the encouraging results obtained in the studies presented in this review justify further development of bacteria as a therapeutic vector against many types of pathology.

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AttenuatedSalmonella entericaSerovar Typhi andShigella flexneri2a Strains Mucosally Deliver DNA Vaccines Encoding Measles Virus Hemagglutinin, Inducing Specific Immune Responses and Protection in Cotton Rats

Cited by 65 publications

References 55 publications

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

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

A Clinical Study to Assess the Safety and Immunogenicity of Attenuated Measles Vaccine Administered Intranasally to Healthy Adults

Bacterial gene therapy strategies

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