Administration, Oral ; Humans ; Rotavirus Infections ; immunology ; prevention & control ; Viral Vaccines ; administration & dosage ; immunology

More than 99% of cervical cancers have been associated with human papillomaviruses (HPVs), particularly HPV type 16. The clear association between HPV infection and cervical cancer indicates that HPV serves as an ideal target for development of preventive and therapeutic vaccines. Although the recently licensed preventive HPV vaccine, Gardasil, has been shown to be safe and capable of generating significant protection against specific HPV types, it does not have therapeutic effect against established HPV infections and HPV-associated lesions. Two HPV oncogenic proteins, E6 and E7, are consistently co-expressed in HPV-expressing cervical cancers and are important in the induction and maintenance of cellular transformation. Therefore, immunotherapy targeting E6 and/or E7 proteins may provide an opportunity to prevent and treat HPV-associated cervical malignancies. It has been established that T cell-mediated immunity is one of the most crucial components to defend against HPV infections and HPV-associated lesions. Therefore, effective therapeutic HPV vaccines should generate strong E6/E7-specific T cell-mediated immune responses. DNA vaccines have emerged as an attractive approach for antigen-specific T cell-mediated immunotherapy to combat cancers. Intradermal administration of DNA vaccines via a gene gun represents an efficient way to deliver DNA vaccines into professional antigen-presenting cells in vivo. Professional antigen-presenting cells, such as dendritic cells, are the most effective cells for priming antigen-specific T cells. Using the gene gun delivery system, we tested several DNA vaccines that employ intracellular targeting strategies for enhancing MHC class I and class II presentation of encoded model antigen HPV-16 E7. Furthermore, we have developed a strategy to prolong the life of DCs to enhance DNA vaccine potency. More recently, we have developed a strategy to generate antigen-specific CD4+ T cell immune responses to further enhance DNA vaccine potency. The impressive pre- clinical data generated from our studies have led to several HPV DNA vaccine clinical trials.
Female ; Humans ; Oncogene Proteins, Viral/genetics/immunology ; Papillomaviridae/*genetics/immunology ; Papillomavirus Infections/immunology/*prevention & control ; Papillomavirus Vaccines/*administration & dosage ; Repressor Proteins ; Uterine Cervical Neoplasms/*prevention & control ; Vaccines, DNA/*administration & dosage ; Viral Vaccines/administration & dosage

OBJECTIVETo construct human metapneumovirus (hMPV) DNA vaccines and evaluate the cellular and humoral immune response in mice.

METHODSFusion protein FdeltaTM (without transmembrane domain) gene and M gene of hMPV were amplified from cDNA by PCR, then DNA vaccines pcDNA3.1His-FdeltaTM and pcDNA3.1His-M were constructed to verify the expression of F and M protein by Western blotting and indirect immunofluorescent assay (IFA) respectively. Serum IgG and spleen cell CTL were detected with ELISA and ELISPOT assay after the BALB/c mice were immunized intramuscularly with the vaccines.

RESULTSThe candidate DNA vaccines could express FdeltaTM and M protein as detected with Western blotting and IFA. The IgG antibody titers of mice was 1:44 when immunized with pcDNA3.1His-FdeltaTM, but could increase to 1:64 when co-immunized with pcDNA3.1His-M. ELISPOT assay demonstrated that IFN-gamma-secreting effector T cells reached 42 +/- 8.9 in co-immunization group, higher than single vaccine pcDNA3.1His-FdeltaTM group (32 +/- 7.4).

CONCLUSIONDNA vaccine pcDNA3.1His-FdeltaTM could induce specific cellular and humoral immune responses, and the immune response could increase when co-immunization with pcDNA3.1His-M was carried out.

Animals ; Antibodies, Viral ; blood ; Female ; Humans ; Immunization ; Metapneumovirus ; genetics ; immunology ; Mice ; Mice, Inbred BALB C ; Paramyxoviridae Infections ; immunology ; prevention & control ; virology ; Vaccines, DNA ; administration & dosage ; genetics ; immunology ; Viral Proteins ; administration & dosage ; genetics ; immunology ; Viral Vaccines ; administration & dosage ; genetics ; immunology

Adjuvants, Immunologic ; administration & dosage ; Administration, Intranasal ; Animals ; Antibodies, Viral ; blood ; Bacterial Toxins ; administration & dosage ; Capsid Proteins ; Enterotoxins ; administration & dosage ; Escherichia coli Proteins ; administration & dosage ; Female ; Hemagglutination Inhibition Tests ; Human papillomavirus 16 ; immunology ; Immunization ; Interferon-gamma ; biosynthesis ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Viral ; genetics ; immunology ; Papillomavirus Vaccines ; Vaccines, DNA ; administration & dosage ; immunology ; Viral Vaccines ; administration & dosage ; immunology ; Virion ; immunology

OBJECTIVEUsing the advantages of Japanese encephalitis live attenuated and inactivated vaccine, to reduce the rate of immunization reaction and to increase the effect, we conducted a study on the strategy of immunization in Japanese encephalitis using live attenuated vaccine combined with inactivated vaccine.

METHODSObserving the safety and immune effects of different groups.

RESULTSData on side effect showed that the rate of moderate and severe systematic reactions of the group who were inoculated with combined vaccine was 0.73%, with local reaction 1.46% while the combined rate of moderate and severe systematic reaction of the group who were inoculated with inactivated vaccine was 2.8%. Under the detection of serum neutralizing antibody, the GMT rose from 1:1.05 - 1:3.35 before vaccination to 1:47.34 - 1:101.30 after vaccination in the different groups. Neutralizing antibody was detected in 97.67% of the combined group. There was a significant difference by comparing neutralizing antibody seroconversion rate of the combined group with the inactivated group (chi(2) = 3.89, P < 0.05), but no significant difference with attenuated group (chi(2) = 0.74, P > 0.05).

CONCLUSIONResults showed that in children who previously had been immunized with two doses of inactivated vaccine, the booster administration of live attenuated vaccine was both effective and safe.

Antibodies, Viral ; blood ; Child, Preschool ; Encephalitis Virus, Japanese ; immunology ; Humans ; Immunization ; Japanese Encephalitis Vaccines ; administration & dosage ; adverse effects ; immunology ; Vaccines, Attenuated ; immunology ; Vaccines, Inactivated ; immunology

Vaccination is one of the most successful applications of immunology and for a long time has depended on parenteral administration protocols. However, recent studies have pointed to the promise of mucosal vaccination because of its ease, economy and efficiency in inducing an immune response not only systemically, but also in the mucosal compartment where many pathogenic infections are initiated. However, successful mucosal vaccination requires the help of an adjuvant for the efficient delivery of vaccine material into the mucosa and the breaking of the tolerogenic environment, especially in oral mucosal immunization. Given that M cells are the main gateway to take up luminal antigens and initiate antigen-specific immune responses, understanding the role and characteristics of M cells is crucial for the development of successful mucosal vaccines. Especially, particular interest has been focused on the regulation of the tolerogenic mucosal microenvironment and the introduction of the luminal antigen into the lymphoid organ by exploiting the molecules of M cells. Here, we review the characteristics of M cells and the immune regulatory factors in mucosa that can be exploited for mucosal vaccine delivery and mucosal immune regulation.
Administration, Oral ; Animals ; Antigens, Bacterial/*immunology ; Antigens, Viral/*immunology ; Bacterial Vaccines/administration & dosage/*immunology ; Humans ; Immunity, Mucosal ; Intestinal Mucosa/cytology/*immunology ; Peyer's Patches/cytology/*immunology ; Viral Vaccines/administration & dosage/*immunology

To investigate the feasibility of using recombinant adeno-associated virus type 1 vector as prophylactic vaccine against HPV16 infection, rAAV1-mod. HPV16L1, the recombinant AAV1 vector containing codon-modified HPV16 L1 gene, was constructed. C57BL/6 mice were immunized with purified rAAV1 vector through intramuscular and intranasal inoculation routes, and the titer of neutralizing antibody was determined by neutralization assay based on HPV16 pseudovirus. The result shows that the single dose of rAAV1-mod. HPV16L1 can induce specific neutralizing antibody in serum through both inoculation routes. Compared with intranasal group, intramuscular group can induce higher titer of neutralizing antibody. Eliciting strong and prolonged neutralizing antibody in serum, the rAAV1-mod. HPV16L1 is one of promising HPV16 prophylactic vaccine candidates.
Animals ; Antibodies, Viral ; blood ; Capsid Proteins ; genetics ; immunology ; Dependovirus ; genetics ; Female ; Mice ; Mice, Inbred C57BL ; Oncogene Proteins, Viral ; genetics ; immunology ; Papillomavirus Vaccines ; administration & dosage ; immunology ; Vaccination ; Vaccines, Synthetic ; administration & dosage ; immunology

This study aims to construct inactivated coxsackievirus A16 (CVA16) vaccine and to investigate its protective effect in ICR mice. A clinical isolate of CVA16, 521-01T, was cultured in VERO cells, inactivated by formaldehyde, and purified by ultracentrifugation for vaccine preparation. Purity and other characteristics of the vaccine were determined by SDS-PAGE and Western blot. Female ICR mice were subcutaneously inoculated with inactivated CVA16 or Al(OH)3-absorbed CVA16, followed by booster immunization at the end of 2 and 4 weeks. CVA16-specific IgG titers in serum were determined by ELISA, and titers of neutralizing antibodies were determined by viral neutralization assay. The immunity of T lymphocytes was evaluated by IFN-gamma ELISPOT assay. The protective effect was evaluated by challenging the neonatal offspring (< 48 hours) of vaccinated female mice with 1 000 LD50 of CVA16 521-01T. The mortality rates of different groups were compared. The results showed that Al(OH)3 +CVA16 could induce high titers of specific IgG antibodies in ICR mice. After being boosted two times, the serum IgG antibody titer could reach up to 1 : 1 x 10(5) (P = 0.000), and neutralizing antibody titer was higher than 1 : 256. Additionally, more spot forming cells were induced in the immunized groups than in the negative controls. The maternal antibodies showed protective effect in 100% of the neonatal mice challenged with 1 000 LD50 of CVA16 521-01T. The inactivated CVA16 vaccine has ideal immunogenicity and immunoprotective effect. This research lays a foundation for the development and evaluation of CVA16 vaccines.
Animals ; Antibodies, Neutralizing ; immunology ; Antibodies, Viral ; immunology ; Enterovirus ; immunology ; Enterovirus Infections ; immunology ; prevention & control ; virology ; Female ; Humans ; Immunization ; Mice ; Mice, Inbred ICR ; T-Lymphocytes ; immunology ; virology ; Vaccines, Inactivated ; administration & dosage ; immunology ; Viral Vaccines ; administration & dosage ; immunology

To evaluate the adjuvant effect of recombinant enterovirus 71 (EV71) subunit vaccine formulated with chitosan, rabbits were orally immunized with recombinant VP1 (rVP1) or rVP1 mixed with chitosan adjuvant. Levels of virus-specific IgG and IgA antibodies in sera, mucosal wash buffer (intestine, nasal cavity, and lung), and feces were determined by indirect enzyme-linked immunosorbent assay (ELISA). The titers of neutralizing antibodies against EV71 were determined using cytopathic effect-based neutralizing assay, and levels of cytokines (IFN-gamma and IL-4) secreted from in vitro-cultured rabbit splenic lymphocytes under antigen stimulation were also determined by ELISA. Results showed that immunization with rVP1 alone could only induce low levels of serum IgG and mucosal IgA, while rVP1 combined with chitosan adjuvant were able to induce significantly higher levels of antibodies, rVP1 can only induce neutralizing antibodies when used in combination with chitosan. Levels of IFN-gamma and IL-4 in the group immunized with rVP1 plus chitosan were significantly higher than those in the group immunized with rVP1 only or those in the control groups. Our study lays the foundation for development of oral VP1 vaccine against EV71 infection.
Adjuvants, Immunologic ; administration & dosage ; Animals ; Antibodies, Viral ; immunology ; Chitosan ; administration & dosage ; immunology ; Enterovirus A, Human ; genetics ; immunology ; Enterovirus Infections ; immunology ; prevention & control ; virology ; Female ; Humans ; Rabbits ; Vaccination ; Vaccines, Subunit ; administration & dosage ; genetics ; immunology ; Viral Proteins ; administration & dosage ; genetics ; immunology ; Viral Vaccines ; administration & dosage ; genetics ; immunology

Despite the intensive vaccination policy that has been put in place to control Newcastle disease virus (NDV), the recent emergence of NDV genotype VII strains in Korea has led to significant economic losses in the poultry industry. We ssessed the ability of inactivated, oil-emulsion vaccines derived from La Sota or Ulster 2C NDV strains to protect chickens from challenge with Kr-005/00, which is a recently isolated Korean epizootic genotype VII strain. Six-week-old SPF chickens were vaccinated once and challenged three weeks later via the eye drop/intranasal route. All vaccinated birds were fully protected from disease, regardless of the vaccine strains used. All vaccinated and challenged groups showed significant sero-conversion 14 days after challenge. However, some vaccinated birds, despite being protected from disease, shed the challenge virus from their oro-pharynx and cloaca, albeit at significantly lower titers than the unvaccinated challenged control birds. The virological, serological, and epidemiological significance of our observations with regard to NDV disease eradication is discussed.
Administration, Intranasal ; Animals ; Chickens ; Cloaca/virology ; Disease Outbreaks/prevention & control/*veterinary ; Korea ; Newcastle Disease/*immunology/prevention & control ; Newcastle disease virus/*immunology ; Ophthalmic Solutions ; Poultry Diseases/*immunology/prevention & control ; *Vaccines, Inactivated/administration & dosage ; Viral Vaccines/*administration & dosage ; Virus Shedding/drug effects