Intramuscular injection of plasmid DNA encoding cottontail rabbit papillomavirus E1, E2, E6 and E7 induces T cell-mediated but not humoral immune responses in rabbits

To test the efficacy of genetic vaccination against papillomavirus infection, plasmid DNA encoding cottontail rabbit papillomavirus (CRPV) E1, E2, E6, E7 or without insert were intramuscularly injected into five groups of rabbits. Peripheral blood mononuclear cells (PBMCs) showed specific proliferation upon in vitro stimulation with E1, E2, E6 or E7 proteins in a majority of vaccinated rabbits but Western blot analysis did not detect antibodies specific for these viral proteins in rabbit serum. All rabbits grew papillomas after virus challenge and none of the rabbits showed systemic papilloma regression. These observations showed that intramuscular injection of plasmid DNA encoding CRPV E1, E2, E6 or E7 induced CD4+ T cell-mediated but not humoral immune responses, and did not result in the protection of rabbits from virus infection.     

Reversal of papilloma growth in rabbits therapeutically vaccinated against E6 with naked DNA and/or vesicular stomatitis virus vectors

Persistent infection with high-risk human papillomaviruses (HPVs) is the greatest risk factor for the development of HPV-associated cancers. In this study rabbits bearing persistent and potentially malignant papillomas were used to test the efficacy of vaccination with a recombinant DNA and/or vesicular stomatitis virus (VSV) targeting the cottontail rabbit papillomavirus (CRPV) E6 protein. Immune responses were primed with either vector and boosted twice with the homologous or heterologous E6 vector. Over the course of 18 weeks, E6 vaccination reduced papilloma volumes to one third the volume in the controls, and the rabbits boosted with an heterologous vector tended to mount stronger responses. Small and medium-sized papillomas responded significantly but only slightly better than large papillomas. Finally the initial papilloma burden per rabbit, ranging from <100 mm³ to >1000 mm³, was not prognostic of antitumor efficacy. In summary both E6 vaccines elicited significant therapeutic immunity, and their sequential use tended to be advantageous.     

Therapeutic vaccination of rabbits with a ubiquitin-fused papillomavirus E1, E2, E6 and E7 DNA vaccine

Previously, we showed that intracutaneous vaccination of rabbits with DNA vectors encoding ubiquitin-fused versions of the cottontail rabbit papillomavirus (CRPV) early proteins E1, E2, E6 and E7 protected against subsequent challenge with CRPV. Here, we tested the immunotherapeutic activity of a vaccine composed of the four CRPV DNA vectors (designated UbE1267) in rabbits. The results show that the UbE1267 DNA vaccine, relative to empty vector DNA, virtually eliminated papilloma growth in rabbits with subclinical infection and greatly reduced papilloma volumes in rabbits bearing papillomas at the time of vaccination. These results in a physiologically relevant animal model of high-risk human papillomavirus (HPV) infection indicate that DNA vaccines targeting the early papillomavirus proteins may have a role in the treatment of HPV-associated lesions in humans.     

Immunization of rabbits with cottontail rabbit papillomavirus E1 and E2 genes: protective immunity induced by gene gun-mediated intracutaneous delivery but not by intramuscular injection

We previously demonstrated that gene gun-based intracutaneous vaccination of rabbits with a combination of, but not with individual papillomavirus E1, E2, E6 and E7 genes provided complete protection against cottontail rabbit papillomavirus (CRPV) infection. In the present study, we tested whether vaccination of inbred and outbred rabbits with a combination of CRPV E1 and E2 genes could provide complete protection against virus infection. In the first experiment, gene gun-based intracutaneous vaccination with E1 and E2 genes prevented papilloma formation in the majority of inbred rabbits and promoted systemic papilloma regression in one non-protected rabbit. In contrast, needle-mediated intramuscular injection of E1 and E2 genes did not prevent papilloma formation nor promoted systemic papilloma regression, indicating an absence of strong protective immunity. In the second experiment, six outbred rabbits were immunized by gene gun-based intracutaneous administration of the E1 and E2 genes. Prevention of papilloma formation or systemic papilloma regression was observed in three vaccinated rabbits. Papillomas persisted on the remaining three rabbits, but were significantly smaller than that on control rabbits. These results suggested that gene gun-based intracutaneous vaccination with the combination of papillomavirus E1 and E2 genes induced strong protective antivirus immunity but may be insufficient for complete protection in an outbred population.     

Immunisation with recombinant BCG expressing the cottontail rabbit papillomavirus (CRPV) L1 gene provides protection from CRPV challenge

Recombinant Bacille Calmette-Guerin (rBCG) could potentially be the vaccine vehicle of choice to deliver foreign antigens from multiple pathogens. In this study we have used the cottontail rabbit papillomavirus (CRPV) rabbit model to provide a "proof of concept" that immunisation with rBCG expressing the CRPV major capsid protein, L1 (rBCG/CRPVL1), will protect outbred New Zealand White rabbits against CRPV challenge. Rabbits immunised with rBCG/CRPVL1 (10(7) cfu/ml) were protected 5 weeks post-CRPV challenge. Rabbits immunised with rBCG/CRPVL1 (10(5) cfu/ml) had papillomas, which were smaller and took longer to appear than the control rabbits. None of the negative control rabbits vaccinated with rBCG expressing an irrelevant gene or PBS were protected from CRPV challenge. Sera from rabbits immunised with rBCG/CRPVL1 (10(7) cfu/ml) were able to neutralise 54.5% of CRPV at serum dilutions of 1:200. These results provide evidence that BCG could potentially be used as a vaccine delivery vehicle for human papillomavirus proteins as a possible prophylactic vaccine.     

Therapeutic efficacy of vesicular stomatitis virus-based E6 vaccination in rabbits

Millions of people worldwide are currently infected with human papillomaviruses (HPVs). A therapeutic HPV vaccine would have widespread applicability because HPV-associated lesions are difficult to treat and may progress to carcinoma. We developed three attenuated VSV recombinants expressing the cottontail rabbit papillomavirus (CRPV) early protein E6 for use as vaccines. In cultured cells, two vectors expressed different levels of the E6 protein, and one expressed a ubiquitin-E6 fusion protein. All three were tested for therapeutic efficacy in the cottontail rabbit papillomavirus (CRPV)-rabbit model. Mock vaccination had no effect on papilloma growth. In contrast, inoculation with any of the VSV-E6 vaccines reduced the rate of papilloma growth to as little as 24% the rate in the controls. In five experiments, these effects were achieved after a single immunization. Furthermore, complete papilloma regression occurred in some rabbits observed for 4 months. A VSV-based papillomavirus E6 vaccine could have significant advantages over other therapeutic HPV vaccine candidates described to date.     

Vaccination inhibits the human adenoviral transduction in a mouse keratoconjunctivitis model

Adenovirus infections are a major cause of epidemic keratoconjunctivitis (EKC), which can lead to corneal subepithelial infiltrates and multifocal corneal opacity. In the current study, we investigated the use of an E1/E3-deleted adenovirus serotype 5 (Ad5) vector as a vaccine administered intramuscularly (IM) or intranasally (IN) against subsequent challenges with a luciferase-expressing Ad5 (Ad5-Luci) vector via eyedrop. We evaluated the adaptive immune response to Ad5 vector vaccination and confirmed a robust polyfunctional CD8 T cell response in splenic cells. Neutralizing Ad5 antibodies were also measured in the sera of vaccinated mice as well as Ad5 antibody in the eye wash solutions. Upon challenge with Ad5-Luci vector 8 weeks post the primary immunization, transduction was significantly reduced by > 70% in the vaccinated mice, which was slightly better in IM- vs. that in IN-vaccinated animals. Resistance to subsequent challenge was observed 10 months post primary IM vaccination, with sustained reduction up to 60% in the Ad5-Luci vector transduction. Passive immunization of naive mice with antisera from IM to vaccinated mice subsequently challenged with the Ad5-Luci vector resulted in approximately 40% loss in transduction efficiency. Furthermore, the mice that received IM immunization with or without CD8 T cell depletion showed > 40% and 70% reductions, respectively, in Ad8 genomic copies after Ad8 topical challenge. We conclude that Ad-vector vaccination successfully induced an adaptive immune response that prevented subsequent Ad transduction in the cornea and conjunctiva-associated tissues in a mouse model of adenovirus keratoconjunctivitis, and that both cellular and humoral immunity play an important role in preventing Ad transduction.     

Protection of rabbits against cutaneous papillomavirus infection using recombinant tobacco mosaic virus containing L2 capsid epitopes

Cottontail rabbit papillomavirus (CRPV) and rabbit oral papillomavirus (ROPV) represent distantly related, cutaneous and mucosal tissue tropic papillomaviruses respectively that can infect the same host. These two viruses were used to test the effectiveness of an L2 peptide-based vaccine (aa 94-122) that was delivered on the surface of recombinant tobacco mosaic virus (rTMV) particles. Groups of NZW rabbits received combinations of CRPVL2, ROPVL2 and CRPV+ROPVL2 rTMV vaccines, and were then challenged with infectious CRPV and ROPV. The rabbits developed antibodies that reacted to whole L2 protein and these sera were able to neutralize CRPV pseudovirions at half-maximal titers that were between 50 and 500. Rabbits receiving the CRPV L2 vaccine alone or in combination with ROPV L2 vaccines were completely protected against CRPV infections. Those rabbits vaccinated with the ROPV L2 vaccines showed a weak response in some rabbits against CRPV infection. These studies demonstrate that L2-based vaccines provide strong protection against experimental papillomavirus infection that is most likely based upon the induction of virus-neutralizing antibody. Notably, we observed some limited cross-protection induced by the L2 sequences tested in these vaccines. Finally, the study demonstrated that rTMV were excellent agents for the induction of strong protection in a pre-clinical disease model of papillomavirus infection.     

Factors associated with complete immunization coverage in children aged 12¿23 months in Ambo Woreda, Central Ethiopia

ABSTRACT: BACKGROUND: Vaccination is a proven tool in preventing and eradicating communicable diseases, but a considerable proportion of childhood morbidity and mortality in Ethiopia is due to vaccine preventable diseases. Immunization coverage in many parts of the country remains low despite the efforts to improve the services. In 2005, only 20% of the children were fully vaccinated and about 1 million children were unvaccinated in 2007. The objective of this study was to assess complete immunization coverage and its associated factors among children aged 12-23 months in Ambo woreda. METHODS: A cross-sectional community-based study was conducted in 8 rural and 2 urban kebeles during January- February, 2011. A modified WHO EPI cluster sampling method was used for sample selection. Data on 536 children aged 12-23 months from 536 representative households were collected using trained nurses. The data collectors assessed the vaccination status of the children based on vaccination cards or mother's verbal reports using a pre-tested structured questionnaire through house-to-house visits. Bivariate and multivariate logistic regression analyses were used to assess factors associated with immunization coverage. RESULTS: About 96% of the mothers heard about vaccination and vaccine preventable diseases and 79.5% knew the benefit of immunization. About 36% of children aged 12-23 months were fully vaccinated by card plus recall, but only 27.7% were fully vaccinated by card alone and 23.7% children were unvaccinated. Using multivariate logistic regression models, factors significantly associated with complete immunization were antenatal care follow-up (adjusted odds ratio(AOR=2.4, 95% CI: 1.2- 4.9), being born in the health facility (AOR=2.1, 95% CI: 1.3-3.4), mothers' knowledge about the age at which vaccination begins (AOR= 2.9, 95% CI: 1.9-4.6) and knowledge about the age at which vaccination completes (AOR=4.3, 95% CI: 2.3-8), whereas area of residence and mother's socio-demographic characteristics were not significantly associated with full immunization among children. CONCLUSION: Complete immunization coverage among children aged 12-23 months remains low. Maternal health care utilization and knowledge of mothers about the age at which child begins and finishes vaccination are the main factors associated with complete immunization coverage. It is necessary that, local interventions should be strengthened to raising awareness of the community on the importance of immunization, antenatal care and institutional delivery.     

Mucosally delivered peptides prime strong immunity in HLA-A2.1 transgenic rabbits

DNA vaccines delivered subcutaneously by gene-gun have generated strong protective and therapeutic immunity in rabbits. Recent studies have shown that peptides delivered by the mucosal routes also stimulate local and systemic immune responses. Since mucosal delivery is easier to administer and more cost-effective when compared to gene-gun delivery, we were interested to learn whether mucosally delivered peptides would prime protective immunity comparable to that of gene-gun-delivered DNA in rabbits. Our newly developed HLA-A2.1 transgenic rabbit model was used to test the hypothesis. We chose an HLA-A2.1 restricted cottontail rabbit papillomavirus (CRPV) E1 epitope (E1/303-311, MLQEKPFQL) for the peptide immunization studies because it provided complete protection when used as a DNA vaccine. Adjuvant has been widely used to boost immunity for vaccines. In this study, three adjuvants reported to be effective for rabbits (TT helper motif, PADRE and CpG2007) were tested with the peptide vaccine. Peptide alone or fused to TT helper or PADRE to create chimeric peptides was delivered by two mucosal routes (ocular and intranasal) together. Partial protection was found in HLA-A2.1 transgenic rabbits when peptide was delivered mucosally in the presence of adjuvant. When a subsequent booster of a half-dose of the corresponding DNA vaccine was delivered, complete protections were achieved. We conclude that mucosal peptide immunization can be combined with a single DNA vaccination to provide strong protective immunity in rabbits.     

Vaccination with a gE-negative bovine herpesvirus type 1 vaccine confers insufficient protection to a bovine herpesvirus type 5 challenge

In the present study, cross-protection to bovine herpesvirus type 5 (BHV-5) induced by bovine herpesvirus type 1 (BHV-1) vaccination was examined following inoculation of rabbits and calves with a glycoprotein E (gE)-negative BHV-1 vaccine and subsequent challenge with BHV-5. Rabbits (n=5) and calves (n=8) were vaccinated [five rabbits intranasally (IN), four calves IN and four intramuscularly (IM)] with 7.1 log(10)median tissue culture infective dose (TCID(50)) of the BHV-1 vaccine. Rabbits and calves were challenged IN [rabbits 2 weeks post-vaccination (pv); calves 5 weeks pv] with 9.1log(10)TCID(50) of BHV-5. Two out of five vaccinated rabbits died after challenge with typical BHV-5 disease, as did 3/5 non-vaccinated controls. In calves, 4/8 vaccinated animals displayed mild signs of disease, whereas 6/6 non-vaccinated controls developed signs of disease, so severe that 2/6 had to be killed. Besides, nasal virus shedding post-challenge was not reduced by vaccination. At necropsy, on day 21 post-challenge, typical BHV-5 lesions were evident in brain tissues of both vaccinated and non-vaccinated calves. Dexametasone administration at 180 days post-infection did not reactivate clinical signs despite BHV-5 shedding in nasal secretions of both vaccinated and non-vaccinated calves. These results show that the BHV-1 vaccine evaluated here did not confer protection to BHV-5 in rabbits. In calves, BHV-1 vaccination did confer some protection to BHV-5 induced clinical disease, but it did not prevent infection and had no effect on nasal virus shedding or on the development of encephalitic lesions.     

Evaluation of the protective effects of a nanogel-based vaccine against rabbit hepatitis E virus

Infection with hepatitis E virus (HEV) has raised serious public health concerns worldwide. In this study, a nanogel-based vaccine encapsulating the capsid protein of rabbit HEV was developed and its protective efficacy was compared with a subunit vaccine. A total of 23 rabbits were divided into 5 groups: (1) negative control (n = 4), (2) positive control (n = 4), (3) nanogel control (n = 5), (4) nanogel vaccine (n = 5), and (5) subunit vaccine (n = 5). Rabbits were vaccinated two times, at weeks 0 and 1, with nanogel and subunit vaccines, respectively, and challenged with rabbit HEV at week 4. By week 11, rabbits vaccinated with the nanogel vaccine produced higher antibodies than those vaccinated with the subunit vaccine. Fecal viral shedding and viremia were identified in rabbits of the positive and nanogel control groups at weeks 6–10. However, there was no viral shedding and viremia in rabbits immunized with both the nanogel and subunit vaccines. Alanine aminotransferase and aspartate aminotransferase levels were not elevated in any rabbit. However, histopathological examination revealed much less hepatic inflammation in rabbits of the nanogel vaccine group compared to the positive and nanogel control groups. Significant increases in IL-12 and IFN–γlevels were identified from rabbits immunized with the nanogel vaccine. Collectively, these results indicate that the newly developed nanogel vaccine induced sufficient immunity leading to complete protection from HEV infection in rabbits. Application of this vaccine should be considered as a preventive measure against HEV infection in other animal species and humans.     

Hepatitis E vaccine immunization for rabbits to prevent animal HEV infection and zoonotic transmission

Hepatitis E virus (HEV) infection has become a significant global public health concern as increasing cases of acute and chronic hepatitis E are reported. HEV of animal origin was proved to be a possible source of human infection and a previous study showed that the recent licensed HEV 239 vaccine can serve as a candidate vaccine to manage animal sources of HEV infection. However, previous immunization strategy for rabbits was the same as that for human, which is too costly to conduct large-scale animal vaccination. In an effort to reduce the costs, three vaccination schemes were assessed in the present study. Forty specific pathogen-free (SPF) rabbits were divided randomly into five groups with eight animals for each and inoculated intramuscularly with different doses of HEV 239 and placebo, respectively. All animals were challenged intravenously with swine HEV-4 and rabbit HEV of different titers 7 weeks after the initial immunization and then fecal virus excretion was monitored for 10 weeks. The results indicated that immunizing rabbits with two 10 μg doses of the vaccine is superior to vaccination with two 20 μg doses or a single 30 μg dose, which can protect rabbits against homologous and heterologous HEV infection. These findings could enable implementation of large-scale animal vaccination to prevent rabbit HEV infection and zoonotic transmission.     

Hepatitis A vaccine in healthy adults: a comparison of immunogenicity and reactogenicity between two- and three-dose regimens

Inactivated hepatitis A virus (HAV) vaccine was administered to 55 healthy seronegative adult volunteers to evaluate the immunogenicity and adverse reactions of two doses of HAV vaccination (25 units) in comparison with a three-dose regimen. The volunteers were randomly assigned to receive one of the two regimens: 26 were vaccinated with two doses at 0 and 24 weeks (Group 1), and 29 were vaccinated with three doses at 0, 2, and 24 weeks (Group 2). The vaccine was well tolerated and there was no serious adverse reaction. In both groups, the seroconversion rate was 100% at week 28. At week 52, all remained positive for anti-HAV regardless of a two- or three-dose regimen. No statistically significant difference in seroconversion rates and geometric mean titers could be demonstrated between the two groups. Thus, the two-dose regimen may be favorable to save cost and time for active immunization against hepatitis A.     

Efficacy and durability of a recombinant subunit West Nile vaccine candidate in protecting hamsters from West Nile encephalitis

The efficacy of a new recombinant subunit West Nile virus (WNV) vaccine candidate was determined in a hamster model of meningoencephalitis. Groups of hamsters were immunized subcutaneously with a WNV recombinant envelope protein (80E) with or without WNV non-structural protein 1 (NS1) mixed with adjuvant or adjuvant alone. At 2 weeks, 6 months, and 12 months after two immunizations at 4 week intervals with the respective immunogens, groups of animals were challenged via the intraperitoneal route with a virulent strain of WNV. The two recombinant antigen preparations gave similar results; hamsters in both groups had a strong antibody response following immunization, and none of the animals became ill or developed detectable viremia after challenge with WNV at 2 weeks or 6 months post-booster vaccination. In contrast, mortality among the control animals at 2 weeks post-booster challenge was 73%, and at 6 months post-booster, the mortality was 53% among the control animals. When challenged 12 months after the booster vaccination, a low level viremia was detected in some of the vaccinated hamsters, and one hamster became sick, but recovered. In contrast, all of the control animals that received adjuvant only developed a viremia, and the mortality rate was 77%. These results with the recombinant subunit WNV vaccine are very encouraging and warrant further animal studies to evaluate its potential use to protect humans against WNV disease.     

Differential determinants and reasons for the non- and partial vaccination of children among Nigerian caregivers

BackgroundVaccination has saved millions of lives. However, the vaccination rate in Nigeria remains low. We differentiate reasons for incomplete vaccination by status: not- and partially- vaccinated, and examine the association between sociodemographic characteristics of caregivers and reasons for incomplete vaccination.MethodsData from the Multiple Indicator Cluster Survey (MICS) conducted in Nigeria in 2016 and 2017 was analyzed. The logistic regression was used to evaluate associations between sociodemographic characteristics of caregivers and incomplete vaccination according to different reasons.ResultsThe most common reason for non-vaccination is that caregivers have no faith in immunization (27.0%), followed by lack of awareness of the need for immunization (26.0%) and the perception that the place where immunization is given is too far/inconvenient (24.3%). The most common reason for partial vaccination is that caregivers thought the children had already been fully immunized (44.8%), followed by the inconvenient location for immunization (15.3%) and supply-side issues such as shortage of vaccine stock and absence of vaccinators (14.4%). Among caregivers whose children are never vaccinated, a lower level of education is correlated with more likelihood of having no faith in immunization and poorer households are more likely to state a lack of awareness of the need for immunization need and an inconvenient place as the reasons for non-vaccination. Among caregivers whose children are only partially vaccinated, educated and wealthier caregivers are more likely to state that they thought their children were fully vaccinated, while poorer caregivers tend to give an inconvenient immunization place as the reason for incomplete vaccination. Supply-side barriers are not systematically correlated with educational attainment or wealth level of caregivers.ConclusionBarriers to vaccination are different according to vaccination status: not- and partially- vaccinated, as is the association between sociodemographic characteristics of caregivers and reasons for incomplete vaccination. The policy to increase vaccination take-up should take these differentials into consideration.     

Durable immunity to oncogenic human papillomaviruses elicited by adjuvanted recombinant Adeno-associated virus-like particle immunogen displaying L2 17–36 epitopes

Vaccination with the minor capsid protein L2, notably the 17–36 neutralizing epitope, induces broadly protective antibodies, although the neutralizing titers attained in serum are substantially lower than for the licensed L1 VLP vaccines. Here we examine the impact of other less reactogenic adjuvants upon the induction of durable neutralizing serum antibody responses and protective immunity after vaccination with HPV16 and HPV31 L2 amino acids 17–36 inserted at positions 587 and 453 of VP3, respectively, for surface display on Adeno-Associated Virus 2-like particles [AAVLP (HPV16/31L2)]. Mice were vaccinated three times subcutaneously with AAVLP (HPV16/31L2) at two week intervals at several doses either alone or formulated with alum, alum and MPL, RIBI adjuvant or Cervarix. The use of adjuvant with AAVLP (HPV16/31L2) was necessary in mice for the induction of L2-specific neutralizing antibody and protection against vaginal challenge with HPV16. While use of alum was sufficient to elicit durable protection (>3 months after the final immunization), antibody titers were increased by addition of MPL and RIBI adjuvants. To determine the breadth of immunity, rabbits were immunized three times with AAVLP (HPV16/31L2) either alone, formulated with alum ± MPL, or RIBI adjuvants, and after serum collection, the animals were concurrently challenged with HPV16/31/35/39/45/58/59 quasivirions or cottontail rabbit papillomavirus (CRPV) at 6 or 12 months post-immunization. Strong protection against all HPV types was observed at both 6 and 12 months post-immunization, including robust protection in rabbits receiving the vaccine without adjuvant. In summary, vaccination with AAVLP presenting HPV L2 17–36 epitopes at two sites on their surface induced cross-neutralizing serum antibody, immunity against HPV16 in the genital tract, and long-term protection against skin challenge with the 7 most common oncogenic HPV types when using a clinically relevant adjuvant.     

Adolescent immunization rates and the effect of socio-demographic factors on immunization in a cosmopolitan city (ERZURUM) in the eastern Turkey

OBJECTIVE: Pediatric vaccinations have decreased the incidence and mortality from infectious diseases in children, but adolescents continue to be adversely affected by vaccine preventable disease. The present study was performed to determine the status of adolescents immunization and to investigate the effect of several socio-demographic factors on immunization. MATERIAL AND METHOD: Using the cluster-sampling method, 817 adolescents were selected in 24 high schools (15,000 students) in central district of Erzurum (Turkey). Adolescents were categorized as completely vaccinated, incompletely vaccinated, unvaccinated or vaccination status unknown. RESULTS: Of the 817 adolescents, 6.9% were completely vaccinated, 24.4% were incompletely vaccinated and 64.1% were unvaccinated. The vaccination status of 4.6% of adolescents was unknown. A significantly correlation was seen between the number of siblings, the level of mother and father education, the level of parent's socio-economics status, health insurance and immunization status. CONCLUSION: Our findings indicated a small percentage of adolescents receive all of the recommended vaccine. In immunization programs in Turkey, priority should be given to increase adolescent immunization rate with a middle school and/or adolescents, vaccination.     

Protective activity and immunogenicity of two recombinant anthrax vaccines for veterinary use

In this study, the efficacy of two experimental vaccines against Bacillus anthracis toxinaemia was evaluated in the rabbit model. A recombinant Protective Antigen (rPA) mutant and a trivalent vaccine (TV) composed by the rPA, a inactive mutant of Lethal Factor (mLF-Y728A; E735A) and a inactive mutant of Edema Factor (mEF-K346R), both emulsified with mineral oils, were evaluated for their immunogenicity and protective activity in New Zealand white rabbits. Rabbits vaccinated subcutaneously with rPA and TV rapidly produced high level of anti-PA, anti-LF and anti-EF antibodies, which were still present 6 months later. In the efficacy test, these vaccines protected 100% of rabbits challenged with B. anthracis virulent strain 0843 one week after the vaccination. Moreover, all animals vaccinated twice with rPA and TV, resisted B. anthracis infection 6 months later. Our data indicate that rPA and TV could be good vaccine candidates for inducing protection against B. anthracis infection in target animal host. They could successfully be used in an emergency with simultaneous long-acting antibiotics to halt incubating infections or during an anthrax epidemic.     

国产麻疹流行性腮腺炎风疹联合疫苗初免效果及免疫程序探讨

目的为观察麻疹、流行性腮腺炎(腮腺炎)、风疹联合疫苗(MMR疫苗)的安全性和免疫原性,并探讨其免疫程序.方法选择91名8月龄儿童,接种MMR疫苗,观察接种后局部反应和全身反应,并检测接种后6周血清麻疹、腮腺炎、风疹抗体阳转率和几何平均滴度(GMT).结果91名8月龄儿童接种MMR疫苗后,有8名儿童发生一过性发热,2名儿童发生皮疹,2名儿童发生局部弱反应.麻疹、风疹、腮腺炎血凝抑制(HI)抗体阳转率分别为98.61%、100.00%、74.07%,GMT分别为145.25、1248.71、14.29.结论MMR疫苗对8月龄儿童接种具有较好的安全性和免疫原性,将其初免月龄定为8月龄儿童是可行的.