Preclinical Safety and Biodistribution of Sindbis Virus Measles DNA Vaccines Administered as a Single Dose or Followed by Live Attenuated Measles Vaccine in a Heterologous Prime–Boost Regimen

The purpose of this work was to assess the ability of plasmid DNA encoding hepatitis B virus (HBV) HBsAg encapsulated in poly(dl-lactide-co-glycolic acid) (PLGA) microparticles to induce local and systemic HBsAg-specific immunity following a single dose of oral immunization. RT-PCR analysis demonstrated prolonged transcription of plasmid DNA, consistent with the sustained expression and presentation of target antigen observed by confocal laser scanning microscopy, in gut-associated lymphocyte tissue (GALT) from mice immunized orally with plasmid DNA encapsulated into PLGA microparticles. Oral administration of PLGA-DNA microparticles induced a long-lasting and stable antigen-specific antibody response, both serum total antibody and intestinal IgA, in BALB/c mice. Mice immunized orally exhibited antigen-specific gamma interferon production and cytotoxic T lymphocyte responses in spleen and GALT after restimulation in vitro with HBsAg or tumour cells stably expressing HBsAg. In contrast, naked DNA vaccines given by intramuscular injection induced only systemic cellular and humoral responses to HBsAg, which were much lower than the responses elicited by oral DNA encapsulated in PLGA microparticles at equivalent doses. The results are encouraging with regard to obtaining good compliance and vaccination coverage with candidate plasmid DNA vaccines, especially in developing countries.

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The association of class I HLA alleles and antibody levels after a single dose of measles vaccine

Human Immunology ◽

10.1016/s0198-8859(02)00741-3 ◽

2003 ◽

Vol 64 (1) ◽

pp. 103-109 ◽

Cited By ~ 38

Author(s):

Robert M Jacobson ◽

Gregory A Poland ◽

Robert A Vierkant ◽

V.Shane Pankratz ◽

Daniel J Schaid ◽

...

Keyword(s):

Single Dose ◽

Class I ◽

Measles Vaccine ◽

Hla Alleles ◽

Antibody Levels

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New preclinical safety evaluation for single-dose clinical pharmacology

Toxicology and Applied Pharmacology ◽

10.1016/0041-008x(74)90020-9 ◽

1974 ◽

Vol 28 (2) ◽

pp. 323-327

Author(s):

G.H. Hottendorf ◽

H. Madissoo ◽

D.R. Van Harken

Keyword(s):

Clinical Pharmacology ◽

Single Dose ◽

Safety Evaluation ◽

Preclinical Safety

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Gamma interferon levels among Bangladeshi children after measles vaccination

Bangladesh Medical Research Council Bulletin ◽

10.3329/bmrcb.v40i3.25234 ◽

2015 ◽

Vol 40 (3) ◽

pp. 118-121

Author(s):

S Sultana ◽

S Tabassum ◽

A Nessa ◽

M Jahan

Keyword(s):

Immune Response ◽

Single Dose ◽

Measles Virus ◽

Mononuclear Cells ◽

Gamma Interferon ◽

Age Group ◽

Measles Vaccine ◽

Live Virus ◽

Significant Difference ◽

Measles Vaccination

Gamma interferon (IFN-?) plays an important role in the immune response to live measles virus vaccination. To study the immune response to measles vaccination, IFN-? level was estimated in 30 children. Of these, 24 children vaccinated with a single dose of measles vaccine at nine months of age and 06 children vaccinated with a second dose during the Measles Catch-up Immunization campaign. Measles vaccine strain was cultured in Vero cell line and the Tissue Culture Infective Dose (TCID)50 was used as standard live virus. Peripheral blood Mononuclear cells (PBMCs) was separated by Ficoll- Hypaque density gradient centrifugation and stimulated with measles virus antigens and mitogens (lectin), cultured in CO2 and IFN-? level was measured from culture supernatant by ELISA. On stimulation with measles antigen and lectin respectively, IFN-? level was highest (105 pg/ml and 226.54 pg/ml) in the 109-120 months age group while it was lowest (12.97±8.16 pg/ml and 13.16±8.0 pg/ml) in the 61-72 months age group. No significant difference was observed in IFN-? level after stimulation with either measles antigen or lectin among well-nourished (p<0.8) and mal-nourished (p<0.7) children suggesting that nutritional status did not have any effect on IFN-? level. However, IFN-? level was higher in children who received two dose of measles vaccine than those who received a single dose (p<0.001).Bangladesh Med Res Counc Bull 2014; 40 (3): 118-121

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A Single Dose of a DNA Vaccine Encoding Apa Coencapsulated with 6,6′-Trehalose Dimycolate in Microspheres Confers Long-Term Protection against Tuberculosis in Mycobacterium bovis BCG-Primed Mice

Clinical and Vaccine Immunology ◽

10.1128/cvi.00148-13 ◽

2013 ◽

Vol 20 (8) ◽

pp. 1162-1169 ◽

Cited By ~ 8

Author(s):

Dyego Carlétti ◽

Denise Morais da Fonseca ◽

Ana Flávia Gembre ◽

Ana Paula Masson ◽

Lívia Weijenborg Campos ◽

...

Keyword(s):

Single Dose ◽

Dna Vaccine ◽

Mycobacterium Bovis ◽

Bacterial Load ◽

Lung Parenchyma ◽

Content Type ◽

Boost Regimen ◽

Trehalose Dimycolate ◽

Tb Infection Control

ABSTRACTMycobacterium bovisBCG prime DNA (Mycobacterium tuberculosisgenes)-booster vaccinations have been shown to induce greater protection against tuberculosis (TB) than BCG alone. This heterologous prime-boost strategy is perhaps the most realistic vaccination for the future of TB infection control, especially in countries where TB is endemic. Moreover, a prime-boost regimen using biodegradable microspheres seems to be a promising immunization to stimulate a long-lasting immune response. The alanine proline antigen (Apa) is a highly immunogenic glycoprotein secreted byM. tuberculosis. This study investigated the immune protection of Apa DNA vaccine against intratrachealM. tuberculosischallenge in mice on the basis of a heterologous prime-boost regimen. BALB/c mice were subcutaneously primed with BCG and intramuscularly boosted with a single dose of plasmid carryingapaand 6,6′-trehalose dimycolate (TDM) adjuvant, coencapsulated in microspheres (BCG-APA), and were evaluated 30 and 70 days after challenge. This prime-boost strategy (BCG-APA) resulted in a significant reduction in the bacterial load in the lungs, thus leading to better preservation of the lung parenchyma, 70 days postinfection compared to BCG vaccinated mice. The profound effect of this heterologous prime-boost regimen in the experimental model supports its development as a feasible strategy for prevention of TB.

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Positive Effect of Single-Dose Measles Vaccination in Reducing the Incidence of Pneumonia in Children with Measles

Journal of Tropical Pediatrics ◽

10.1093/tropej/fmaa085 ◽

2020 ◽

Author(s):

Zafer Bağcı ◽

Yunis Yusuf Daki

Keyword(s):

Single Dose ◽

Length Of Hospital Stay ◽

Vaccination Rate ◽

Hospitalization Rate ◽

High Morbidity ◽

Measles Vaccine ◽

Hospitalization Rates ◽

Training And Research ◽

Measles Vaccination ◽

Positive Effect

Abstract Aim Measles is a worldwide common, highly infectious and vaccine-preventable contagious disease with high morbidity and mortality rates. We investigated the effects of administering single-dose measles vaccination in children with measles on the incidence of pneumonia and hospitalization. Materials and methods We retrospectively analysed the hospital records of children aged 0–18 years who were diagnosed with measles within a year before the study in a training and research hospital in Mogadishu, Somalia. We compared the measles vaccine ratios, hospitalization rates, hospitalization duration and pneumonia development rates. Results We found that 34 (15.6%) patients had received measles vaccination, while 184 (84.4%) did not receive the vaccination. All the vaccinated patients received only a single dose of the vaccine. The proportion of those who had received pneumonia vaccine (14/34, 41.2%) was significantly lower than that of those who had never received a dose of measles containing vaccine (179/184, 97.3%) (p = 0.001). Moreover, patients who were immunized [n = 3 (3.1%)] had a significantly lower hospitalization rate than those who were not immunized [n = 94 (96.9%)] (p = 0.001). Conclusion The risk of pneumonia in children with measles vaccination, rate of hospitalization and length of hospital stay was significantly lower in children who had received even a single dose of the vaccine when compared with that in those who had not vaccinated. The results of this study reiterate the need for more effective global measles vaccination.

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Measles seroprevalence of an adolescent population vaccinated with a single dose of measles vaccine before their first birthday

International Journal of Adolescent Medicine and Health ◽

10.1515/ijamh.2005.17.4.337 ◽

2005 ◽

Vol 17 (4) ◽

Author(s):

Nuray Öksüz Kanbur ◽

Orhan Derman ◽

Tezer Kutluk

Keyword(s):

Single Dose ◽

Measles Vaccine ◽

Adolescent Population

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Preclinical toxicological evaluation of measles virus vaccine strain in non-human primates: A two-month intravenous study

Biomedical Research and Therapy ◽

10.15419/bmrat.v8i6.676 ◽

2021 ◽

Vol 8 (6) ◽

pp. 4382-4393

Author(s):

Dang Thanh Chung ◽

Ho Thi Long ◽

Hoang Van Tong ◽

Ngo Thu Hang ◽

Ngo Thu Huong ◽

...

Keyword(s):

Vaccine Strain ◽

Measles Virus ◽

Safety Data ◽

Safety Evaluation ◽

Post Injection ◽

Measles Vaccine ◽

Igg Antibody ◽

Toxicological Evaluation ◽

Target Organs ◽

Preclinical Safety

Introduction: Based on its ability to kill tumor cells, the vaccine strain of the measles virus is used for oncolytic virotherapy. However, the dose required for cancer therapy is much higher than that used for vaccination. Therefore, this study was conducted to evaluate the preclinical toxicology of the vaccine strain of measles virus in monkeys. Methods: 16 healthy Macaca mulata monkeys were randomly divided into four groups, of which one was a control. A preclinical safety evaluation of the vaccine strain of the measles virus was performed, and the three experimental groups were intravenously injected with the strain at doses of 105 TCID50, 106 TCID50 and 107 TCID50 respectively. Results: There were no significant abnormalities in the physical, clinical, haematological, and biochemical parameters following the intravenous injection with measles vaccine at doses of 105 TCID50, 106 TCID50 and 107 TCID50. The vaccine strain of measles virus remained in the plasma until the 30th day and disappeared on the 60th, and it did not persist in the tissues on days 30 and 60 post injection. Measles IgG antibody was negative on days 0, 1, 3, and 8 and was positive on days 15, 30, and 60 post administration of the measles virus. The histopathology of target organs was not affected in all groups on days 30 and 60 post injection. Conclusions: The systematic preclinical safety data of the present study confirms the safety of two months of concentrated measles vaccine administration in the Macaca mulata monkey for clinical trials.

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Sindbis Virus-Based Measles DNA Vaccines Protect Cotton Rats against Respiratory Measles: Relevance of Antibodies, Mucosal and Systemic Antibody-Secreting Cells, Memory B Cells, and Th1-Type Cytokines as Correlates of Immunity

Journal of Virology ◽

10.1128/jvi.02191-08 ◽

2009 ◽

Vol 83 (6) ◽

pp. 2789-2794 ◽

Cited By ~ 18

Author(s):

Marcela F. Pasetti ◽

Karina Ramirez ◽

Aldo Resendiz-Albor ◽

Jeffrey Ulmer ◽

Eileen M. Barry ◽

...

Keyword(s):

B Cells ◽

Virus Vaccine ◽

Neutralizing Antibodies ◽

Measles Virus ◽

Sindbis Virus ◽

Dna Vaccines ◽

Memory B Cells ◽

Cotton Rats ◽

To Receive ◽

Antibody Secreting Cells

ABSTRACT Measles remains an important cause of pediatric morbidity and mortality in developing countries, especially among infants who are too young to receive the current licensed live attenuated measles vaccine. We developed two Sindbis virus DNA vaccines encoding the measles virus hemagglutinin (pMSIN-H) and fusion proteins (pMSINH-FdU) and examined their immunogenicities and protective efficacies when administered alone or followed by the live measles virus vaccine in cotton rats. Neutralizing antibodies, mucosal and systemic antibody-secreting cells, memory B cells, and gamma interferon-secreting T cells developed after priming and increased after boosting. pMSIN-H priming conferred 100% protection against pulmonary measles, whereas pMSINH-FdU protected only in conjunction with the live measles virus vaccine boost.

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