Epidemic management in a measles outbreak in 2023,the return of vaccine-preventable diseases:A single center,retrospective observational study

Objective:To investigate the importance of immunization in preventing measles infection and to determine the most useful laboratory tests for confirmation of measles.Methods:This study included pediatric cases evaluated with a presumed diagnosis of measles between December 2022 and June 2023,at Marmara University Pendik Training and Research Hospital.The effects of vaccination status and underlying disease on the clinical course,treatments,and complications were evaluated.Results:In total,117 patients were enrolled in the study with a median age of 80 months(IQR:32.5-125.0).Twelve patients with contact history were asymptomatic and had an underlying disorder,and intravenous immunoglobulin was given to them for post-exposure prophylaxis.Fifty-one patients had confirmed measles diagnosis.Ribavirin treatment was given to three patients(a newborn,a girl with rhabdomyosarcoma,and a healthy boy)with respiratory distress.Seventy-eight percent of confirmed measles cases were unvaccinated,and all hospitalized cases were unvaccinated or under-vaccinated.Four full-vaccinated children had confirmed measles infection.Measles PCR from nasopharyngeal swabs was negative in all of them,and their diagnosis was established with anti-measles IgM positivity.Conclusions:The measles vaccine is the most effective way to protect from measles and measles-related complications.Although measles can also occur in fully vaccinated patients,the disease is milder than in unvaccinated patients.Using ELISA and RT-PCR tests together may be beneficial in patients with high clinical suspicion for early diagnosis.

Vaccination and Measles Epidemic in the Republic of Congo

Measles is a highly infectious, vaccine-preventable viral disease. Often forgotten, it is potentially fatal. Its main symptoms are: fever, cough, conjunctivitis, rhinitis and skin rash. Serological diagnoses by ELISA test based on the detection of anti-measles virus immunoglobulins M and G (IgM and IgG), are used respectively for the confirmation of suspected cases notified by means of clinical signs of the disease in health structures of the twelve departments of the Republic of Congo involved in the epidemiological surveillance of the disease, and for the evaluation of the immunity conferred by vaccination. During 2021, 459 suspected cases of measles were reported and sampled throughout the country, despite the administration under the Expanded Routine Immunization Program (EPI), of 2 doses of the combined measles-rubella vaccine (RR1 and RR2) in 2020. The notification rate was higher in the south of the country, more precisely in the health structures of the departments of Pointe-Noire (42%) and Brazzaville (11%). During the year 2021, 459 suspected cases of measles were notified and sampled throughout the country with a high notification rate in the south of the country, more precisely in the health structures of the Pointe-Noire departments (42%) and Brazzaville (11%). The samples consisting of human blood (serum) were sent to the National Public Health Laboratory and analyzed by various ELISA tests for the detection of anti-measles immunog-lobulins M and G. The analysis of the results obtained shows that the measles virus circulated in all departments of the country. 154 cases (33.55%) were confirmed positive by IgM ELISA and 98 positive cases (63.63%) were patients vaccinated against measles. Vaccination coverage in RR1 of [50%-95% [(first dose) as well as the lowest RR2 < 50% (second dose) undoubtedly because the COVID-19 pandemic could be the cause of the high frequency of cases positive vaccinated. The non-detection of IgG immunoglobulins in vaccinated patients observed by IgG ELISA tests revealed that 63.26% of vaccinated patients were not immunized against the measles virus. These results confirm those obtained during the Elisa IgM analysis and make it possible to deduce that the quality, the number of doses not properly administered, the individual characteristics of the people as well as the poor conservation of the administered vaccine (non-compliance with the cold chain) would explain the high proportion of positive cases of vaccinated measles observed.

Knowledge and associated factors of healthcare workers on measles vaccine and cold chain management at health institutions in Gondar,Ethiopia

Objective:To assess the knowledge of healthcare workers on the measles vaccine and its cold chain management.Method:An institutional-based cross-sectional study was conducted from February 1 to March 30,2022 in Gondar City Administration public health institutions among 165 healthcare workers.Data were collected using a structured questionnaire.In addition,an on-spot observation checklist was used to assess the availability,status and management of the cold chain.A logistic regression model was used to assess the relationship between the outcome and predictor variables.Crude and adjusted odds ratios were calculated with 95%confidence intervals.Results:Overall,87(52.7%;95%CI 44.8%-60.5%)of the healthcare workers had unsatisfactory knowledge regarding the measles vaccine and its cold chain management.One hundred thirty-six(82.4%)healthcare workers correctly mentioned the recommended range of temperature(2-8℃)for measles vaccine storage.Healthcare workers aged 18-29 years(P=0.001)and 30-44 years(P=0.014)were observed as determinants of unsatisfactory knowledge on the measles vaccine and its cold chain management.One hundred and five(63.6%)of the healthcare workers did not correctly mention the type of measles vaccine used in routine immunization.More than one-third(36.4%)of the healthcare workers perceived that the measles vaccine is not safe and could cause measles.Conclusions:More than half of the healthcare workers in the study area had unsatisfactory knowledge on the measles vaccine and its cold chain management.It is necessary to provide technical support and in-service training for healthcare workers to ensure optimal immunization effectiveness.

Primary Research of Immunological Mechanism of Combined Hepatitis A-Measles-Varicella Vaccine

To explore the primary humoral and cellular immunological mechanism of the combined hepatitis A-measles-varicella vaccine, the mice were inoculated with hepatitis A-measles-varicella vaccine by intraperitoneally and two weeks later, blood was collected to observe the mice＇s immunological status. Antibody level was measured to appraise the humoral immunity. At the same time, T lymphocyte surface marker, NK cell activity, LAK cell activity, delayed type hypersensitivity of skin, Mφ phagocytic function, mRNA level of cytokine IL-2 and IFN-γ plus lymphocyte transformation test were used to analyze the cellular immunity. The humoral immunity results show that the combined hepatitis A-measles-varicella vaccine produce the same antibody level as their corresponding univalent vaccine, and maintained fine immunogenicity and security. The result of cellular immunity shows that the combined vaccine could activate physical immunocyte, increase the regulative ability of cytokine, enhance the physical immune function and immune defense ability. The present research proved the security and better humoral and cellular immunity of combined hepatitis A-measles-varicella vaccine from the immunological point of view, which laid good foundation for further study and development.

Contributions of the Measles Follow-Up Vaccination Campaign to Improving the Vaccination Coverage of Children Aged 6 - 59 Months in the Democratic Republic of the Congo in 2019

Background: In accordance with its measles elimination strategic plan 2012-2020, the Democratic Republic of the Congo (DRC) organized a follow-up vaccination campaign against measles from October to December 2019 in 26 provinces. This study aims to establish the contribution of this supplementary vaccination campaign to protecting children against measles. Methods: The survey was carried out in November 2020 among households of the DRC, according to the 2018 revised version of the World Health Organization’s stratified cluster sampling method, using multiple stage sampling. It targeted 280 children aged 6 - 59 months per stratum or province, with 10 children in each of the 28 selected clusters. Data collection using tablets with centralized and real-time data processing was preceded by enumeration to refine the household sampling frame. Clusters and households were selected by random draw. Data collected with CS Pro 7 software were analyzed with SPSS, Epi info 7 and Excel software to determine indicators and make before-after comparisons using the McNemar test, at a precision threshold of 5%. Results: Of the 8535 surveyed children, 89.5% were vaccinatedduring the follow-up campaign and 81.6% were vaccinated before. Only 3.7% had correctly completed campaign vaccination cards. Estimated vaccination coverage increased from 80.8% before the campaign to 92.6% after the campaign (p 0.001). Vaccination coverage after campaign against measles improved in all provinces (p < 0.001) except Bas-Uele and Maniema. Thirteen provinces reached the national coverage target of 95%, compared to five before the campaign. The proportion of zero-dose children dropped significantly after this campaign from 19.2% to 7.4% (p 0.001), and even fell below 1% in six provinces. Conclusion: This measles vaccination campaign improved overall vaccination coverage by 10% and reached more unvaccinated children. Efforts must continue to improve the retention of vaccination card, the adherence of unvaccinated children and the effectiveness of routine vaccination.

Measles Virus IgG Avidity Assay for Use in Identification of Measles Vaccine Failures in Tianjin, China

Objective To identify measles vaccine failures in Tianjin, China using a measles virus Ig G avidity assay.Methods The China Information System for Disease Control and Prevention(CISDCP) was used to collect information about measles cases and blood specimens in Tianjin from 2013 to 2015. Measlesspecific Ig M and Ig G antibodies were detected using Enzyme-Linked Immunosorbent Assay(ELISA).Avidity testing for measles Ig G was performed using a commercial enzyme immunoassay(EIA).Results A total of 284 confirmed measles cases were identified. Of this total, 262(92.25%) were in patients aged ≥ 20 years. High avidity was exhibited in 172(60.56%) cases, while 80(28.17%) cases demonstrated low avidity. High avidity was detected in only 21.43% of cases in patients aged < 1 year.The proportion of high avidity increased with age, and was significantly higher in patients aged 30–39 years at 70.07%(χ~2 = 17.27, P = 0.002). Of the 52 measles cases in patients with a history of vaccinations,41(78.85%) cases showed high avidity, indicating secondary vaccine failures(SVF). In these vaccinations,there was no significant difference(P > 0.05) in clinical severity between high avidity and low avidity cases. However, regardless of vaccination status, clinical severity was significantly lower in high avidity cases(P < 0.001) than in low avidity cases. The percentages of positive measles Ig M results in high avidity and low avidity cases were 66.28% and 91.25%, respectively. Geometric Mean Concentration(GMC) was significantly lower in high avidity cases at 33.73 U/m L, compared to 166.07 U/m L in low avidity cases.Conclusions Low clinical severity and inconclusive Ig M antibody results are more likely in high avidity measles cases. Measles cases were more common in adults. Therefore, a further dose of vaccines should be recommended for 30–39 years in Tianjin.

Clinical Trial of Measles and Rubella Combined Vaccine Produced by POLYVAC in Vietnam

A clinical trial of measles and rubella combined vaccine (MR: MRVAC) produced by POLYVAC was conducted in Vietnam in 2016. A total of 756 subjects were enrolled, and 504 were allocated to MRVAC and 252 to control MR vaccine groups. Paired sera were obtained in 733, and the number of subjects was 403 aged 1 - 2 years, 164 aged 2 - 18 years, and 166 aged 18 - 45 years. Antibodies against measles and rubella viruses were evaluated by EIA. Most subjects had been immunized with a single dose of Expanded Programme on Immunization (EPI) measles vaccine at 9 months of age. Only 41 of 403 subjects aged 1 - 2 years were negative for measles antibody before vaccination, and all became seroconverted. A serological response of more than a 2-fold increase against measles was noted in 214 (47%, 95% CI;42.4% - 51.6%) of 458 initially seropositive individuals immunized with MRVAC and 65 (28%, 95% CI;22.3% - 33.8%) of 234 in the control group, and geometric mean titer (GMT) after vaccination was 25.49-5.60 in MRVAC and 25.03-5.24 in control group. Seroconversion against rubella virus after immunization with MRVAC was noted in 267 (98.5%, 95% CI;97.1% - 100%) of 271 initially seronegative subjects, similar to that after immunization with control group. GMT after immunization with MRVAC was 24.88-5.11 significantly lower than that after immunization with control vaccine (25.59-5.80). Most subject ≥ 2 years of age had rubella antibody because of MR vaccination campaign and no significant serological response was observed in initially seronegatives. MRVAC was highly immunogenic and safe vaccine and the domestic production of MR vaccine would contribute to realizing the goal of eliminating measles and rubella.

Epidemic Outbreaks in Plovdiv Region (Bulgaria) of Vaccine-Preventable Diseases: Measles, Mumps, Hepatitis A

Aim: To analyze the reasons for epidemic outbreaks of measles, mumps and viral hepatitis A and to propose measures to prevent them in future. Materials and methods: Тhe incidence of measles, mumps and hepatitis A in Plovdiv region was studied for the period 2006-2010. An analysis of the age structure of the patients was made, while taking into account the time for routine immunization performed against measles and mumps (first and second dose). Results: In 2006-2009 single cases of measles were found occasionally, but in 2010 they were 2787 (incidence 395/100,000). Most of them (51%) were for ages 13 months-12years, 27%-0-13 months and 11%-13 to 18 years. The incidence of mumps for 2006-2010 varied widely, and has increased significantly in 2007 (130/100,000) and 2008 (169/100,000). The majority of patients (over 34%) during the epidemics were aged 13 months-12years, and over 26% of them-13-19 years. For the period 2006-2010 the incidence of hepatitis A ranged from 2.98/100, 000 (2009) to 426/100,000 (2006). Over 50% of the cases involved children aged up to 9 years. For the three diseases over 80% of patients were individuals of Roma origin. Conclusions: 1. Epidemic spread of measles in 2010 was mainly due to shortcomings in the routine immunization carried as a prevention of the disease. 2. There are two reasons for the outbreak of mumps: А) Failure to administer the second vaccine dose at 12 years in Bulgaria until 2001. B) Shortcomings in routinely performed immunization. 3. The extremely high incidence of hepatitis A in 2006 (and in the rest of the years) is due to the lack of routine immunization. 4. Essential for the outbreaks in all three diseases are the poor hygienic living conditions, the low social status and the lack of health promotion of the population at risk 5. To prevent future outbreaks of the diseases hereby in question, we suggest it is appropriate: А) To introduce compulsory immunization against hepatitis A;B) To carry out periodic catch-up vaccination campaigns against measles and mumps.

Immunological Adjuvant Function of Aluminium Phosphate and Chicken IL-18 in NDV F Gene Vaccine

[Objective] This study aimed to investigate the immunological adjuvant function of aluminium phosphate and chicken IL-18 in NDV F gene vaccine. [Method] The vaccine （0.2 ml） containing aluminum phosphate adjuvant （90 μg）, pcDNA/F （200μg）, and pcDNA/chlL-18 （200 μg） was prepared. The 7 d old chick- ens to be tested were randomly divided into six groups （12 chickens in each group） and immunized through intramuscular injection with inactivated Newcastle disease vaccines, pcDNA/F＋pcDNA/chlL-18＋phosphate aluminum, pcDNA/F, pcDNA/F.＋pcDNA/ chlL-18, pcDNA/F＋aluminum phosphate, and physiological saline respectively; the secondary immunization was conducted with the same dose when the chickens were 21 d old. Their blood was sampled 0, 7, 14, 21, 28 d after first immunization. Anti- body titer was detected with ELISA and T cell transformation rate was measured with MIT. Experimental chicken will be challenged with 30 LD50 NDV virulence 28 d after first immunization. [Result] The survival rate of the chickens immunized with pcDNA/F＋aluminium phosphate＋pcDNA/chlL-18 achieved 8/12, higher than that of those immunized with pcDNA/F 4/12 and pcDNA/F＋pcDNA/chlL-18 （6/12）. The NDV antibody titer of the chickens immunized with pcDNA/F＋ aluminum phosphate, pcD- NA/F＋pcDNA/chlL-18 and pcDNA/F＋pcDNA/chlL-18＋aluminum phosphate is not differ- ent （P〉0.05）, but significantly lower than that of the chickens immunized with tradi- tional vaccine （P〈0.05）. The T cell transformation rate of the chickens immunized with pcDNA/F＋pcDNA/chlL-18＋aluminium phosphate was obviously higher than that of the chickens immunized with pcDNA/F （P〈0.05）. The T cell transformation rates of chickens immunized with pcDNA/F and the traditional vaccine showed no signifi- cant difference （P〉0.05）. [Conclusion] Combination of aluminium phosphate and pcD- NA/chlL-18 can significantly enhance the immune effect of NDV F gene vaccine.

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

Correlates of first dose of measles vaccination delivery and uptake in Indonesia

Objective:To determine health systems-related,familial,and cultural factors which influence the delivery and uptake of measles vaccination in Indonesia.Methods:Logistic regression analysis of data collected during the 2007 Indonesian Demographic and Health Survey was undertaken by the authors to investigate these factors.The 2007 Indonesian Demographic and Health Survey dataset is a nationally representative,randomly sampled survey containing 15 065 children aged between 9 and 59 months.Results:72.8%of children had received the measles vaccine.Vaccination coverage was similar for males and females;however,coverage was higher amongst urban children,80.1%,compared to 68.5%in rural areas.The key findings of the regression analysis were congruent with the results of previous research targeting vaccination coverage.After controlling for all other factors,maternal age,maternal education,wealth, the use of a skilled birth attendant,and postnatal check-ups were positively and significantly (P【 0.01) correlated with measles vaccination.The number of children per household was negatively correlated(P【0.01).Conclusions:In order to enhance measles vaccination coverage in Indonesia,delivery to,and uptake by,rural and low socio-economic populations require substantial improvements.Mass health education and health systems improvements are also required.

Relationship between Self-Reported Vaccination History and Measles and Rubella Antibody Titers in Medical and Nursing Students

In hospitals, infection control for measles and rubella is important. Medical and nursing students as well as healthcare workers must have immunity against these diseases. Many countries have adopted requirements for healthcare workers’ documented vaccination history or laboratory tests as evidence of their immunity. Evaluating a written vaccination history is difficult in many cases. Therefore, we compared measles and rubella antibody titers with self-reported vaccination history and we evaluated the association between the history and measles and rubella antibody titers, using the medical and nursing students’ data. We analyzed 564 data for measles and 558 data for rubella. Vaccination history was requested to be completed as accurately as possible. Students with one or more measles or rubella vaccinations had high positive ratios of titer, and the ratio was significantly higher than that of the students without vaccinations. The positive ratio between the two-dose and one-dose vaccination groups was not significantly different for measles or rubella (measles: p = 0.534, rubella: p = 0.452). Although it should be requested that the history is complete by using other resources, such as referring to maternity passbooks or proof of vaccination, self-reported history may be useful to confirm immunity, even if there is a possibility that the history is not accurate.

A Comparative Study on the Hemato-Biochemical and Immunological Effects of the Hexavalent FMD Vaccine Alone or in Combination with Trivalent FMD Vaccine in Cattle

Foot and mouth disease is the most contagious disease of mammals and has a great potential for causing severe economic loss in susceptible cloven-hoofed animals. Routine prophylactic vaccination in Egypt from 2012 till now has been conducted with Trivalent and/or hexavalent vaccine of MERIAL, against virus strains (O manisa + O-3039 + A Iran 05 + A Saudi 95 + Asia 1 + Sat2). This study aimed to evaluate the hemato-biochemical and immunological changes associated with the use of hexavalent vaccine alone or in combination with trivalent FMD vaccine. This study was carried out on 24 cattle divided into three groups eight cattle each. Group I served as control. Group II were selected from farms vaccinated with hexavalent FMD vaccine. Group III were selected from farms vaccinated with a combination of trivalent and hexavalent FMD vaccine. The results showed that both vaccinated groups showed a significant increase in total leukocytic count. Sera from hexavalent-trivalent vaccinated cattle demonstrated a significant increase in serum cortisol concentrations. Significant increase in serum activity of aspartate aminotransferase was recorded in animals vaccinated with a combination of hexavalent and trivalent vaccine. In addition, both regimes resulted in a significant increase in serum blood urea nitrogen compared to control. Both regimes induced a significant increase in serum levels of ceruloplasmin while phagocytic activity of neutrophils and phagocytic index was enhanced only by the hexavalent vaccine. Both vaccinated groups had significantly increased serum values of gamma globulins. These results suggested that hexavalent vaccine produced higher levels of safety and protective effects against FMD in cattle as compared to those produced by a combination of hexavalent and trivalent vaccines. It is also advisable to include the hexavalent vaccine within the program of obligatory and imperative vaccination against FMD.

Enlightenment and Reference of Vaccine Clinical Trial Design Based on Immunological Surrogate Endpoints in the United States

Objectives To explore the optimization method of vaccine clinical trial design based on immunological surrogate endpoint to improve the quality and efficiency of vaccine clinical research and development.Methods As to the problems in the vaccine clinical research in China,the relevant guidelines and literatures of FDA and WHO were used to analyze and summarize the methods of optimizing the design of vaccine clinical trials.Results and Conclusion The adaptive design guidelines are established to guide clinical trial design,encourage the development and application of immunological surrogate endpoints,establish qualification process for drug development tools and information disclosure procedures to improve vaccine development efficiency.

Cancer vaccines: prospects and problems

Cytokines provided locally at tbe tumor site mayinitiate an effective anti-tumor immune responsewhich leads to rejection of a tumor which otherwisegrows progressively. Experimentillly, this can betested by gene transfer into cultured tumor cellsfollowed by the analysis of the tumorigenicity of suchgenetically engincered cells. This approach allows

In Vivo Kinetics and Biodistribution of a Hantaan Virus DNA Vaccine after Intramuscular Injection in Mice

To study the kinetics in vivo of a Hantaan virus DNA vaccine, we constructed a fusion DNA vaccine, pEGFP/S, by cloning the S segment of Hantavirus into the vector, pEGFP-C1, which encodes Green fluorescent protein EGFP. In this report, we provide evidence that pEGFP/S was distributed and persistently expressed for more than 60 days in several organs after inoculation. Our findings suggest that the persistent immune responses induced by a Hantaan virus DNA vaccine are likely due to the plasmid pEGFP/S deposited in vivo, which acts as a booster immunization.

Controlling Dengue: Effectiveness of Biological Control and Vaccine in Reducing the Prevalence of Dengue Infection in Endemic Areas

With the increased prevalence of dengue infection in tropical countries, concerned members of the public are now pressing their local health ministries to act immediately and effectively in managing the rising numbers of reported cases. This includes reviews of the methodologies and the effectiveness of current combative systems to find other possible novel approaches that might yield better results. One of those novel approaches is the integration of a parasite into mosquito vector, manipulating the parasite-host interaction to reduce the transmission of dengue in endemic hotspots. Another alternative is by Sanofi-Pasteur’s dengue vaccine that showed over 60.8% success rate in reducing severe dengue infection in children aged 9 - 16 during its final clinical implementation phase. This report will compare and contrast these two novel ideas to determine which of the approaches are more likely to be effective in the long run. The aspects covered will include the application, effectiveness, functionality, and problems with these approaches. The results could then be utilised by governments or organizations to select precise and effective methods in reducing the prevalence of dengue infections in their countries.

Measles in a Neonatal Unit during Epidemic Period in 2011

The incident of the measles has diminished in the last decades thanks to the widespread use of the vaccine in The United States and Europe. Nevertheless, recently we are seeing new epidemics of measles due to the lack of coverage in some social areas. Measles during pregnancy is associated with high maternal morbidity and mortality, being a frequent cause of abortion in preterm deliveries. We report two cases of measles attended in the Unit of Neonatology held coinciding with the epidemic lived in this area during the last year.

Evaluation of the Kinetic Change of the Immunogenicity of Dengue-2 DNA Vaccine in Mice Administered by Different Administration Routes

A plasmid DNA vaccine is able to induce both humoral and cellular immune responses;however, the kinetic change of the Th1/Th2 response, antibody avidity, cytokine secretion, and neutralization activity after different priming and boosting strategies have not been evaluated. A plasmid DNA, designated pCBD2 and previously shown to efficiently induce an immune response very similar to that by a wild type virus, was evaluated kinetically in this study. Our results suggest that a DNA vaccine delivered by the gene gun (gg) route produced higher and longer DENV-2-specific antibody titers than those induced through the intramuscular (im) route. Although the gg group induced a Th2 response and im delivery induced a Th1 response, priming by gg delivery, followed by a boosting by im delivery, did not shift the immune response from a Th2 to Th1 response. Furthermore, the antibody avidity (AI) measured by ELISA demonstrated a gradual increase of AI from low (AI range from 6.8% - 9.6%) on day 42 to high (AI value > 30) on day 119 in all but the gene-gun immunization group, in which an AI value of 23 was observed. Although there was lower avidity in the gg group, the mice sera from all three groups of mice demonstrated significant neutralization activity. This is the first report about the kinetics of immunogenicity of a DNA vaccine through different administration strategies, which suggests that gene gun delivery of a DNA vaccine can induce an immune response containing both neutralizing and nonneutralizing antibodies at high titers important for neutralization.