A new rabies vaccine in public health practice in the USSR

A new antirabies vaccine prepared on the basis of virus grown in the ovine brain, purified from 85-90% of brain-tissue ballast substances and inactivated with beta-propilactone has been developed at the Moscow Research Institute of Viral preparations (USSR Acad. Med. Sci.). The preparation produces no neuro-allergenic effect in tests on guinea pigs. When injected to humans, the vaccine shows much lower reactogenicity than Fermi vaccine. High antigenic and immunogenic activity of the new vaccine has made it possible to work out a less intensive immunization schedule in comparison with that used for immunization with Fermi vaccine and nonconcentrated tissue-culture vaccine, viz. doses of 3 ml for 12 days or doses of 3 ml for 20 days with two booster immunizations. The preparation has been introduced into medical practice.     

Studies of the effects of BCG and Corynebacterium parvum vaccines in experimental infection of mice with influenza virus. Foot pad test, splenic indicator and histologic changes in the thymus gland, spleen and lymph nodes

Evaluation of the influence of BCG and Coparvax on reticulo-endothelial system in mouse was performed. Mice were stimulated i.p. with BCG vaccine and Coparvax vaccine. Spleen index and histological changes in thymus, spleen and lymph nodes were evaluated after 14 days in mice vaccinated with BCG and after 7 days in mice vaccinated with Coparvax. Foot pad test was also performed by giving vaccine into three feet. Tuberculin was injected into mouse foot pad on the day 7th and 14th and a lysate of Coparvax vaccine on the day 7th. Spleen index and foot pad test showed higher values in mice vaccinated with Coparvax than with BCG. Histological changes of thymus, spleen, and lymph nodes showed morphological differences depending on the type of vaccine used. Both preparations were characterized by stimulating effect on reticuloendothelial system, which was much more pronounced after giving Coparvax vaccine.     

人狂犬病免疫球蛋白使用效果观察

为了解人狂犬病免疫球蛋白的作用效果,我们将观察对象随机分成了A、B、C三组,分别采用三种措施进行狂犬病的预防治疗,即：A组联合使用狂犬病疫苗与人狂犬病免疫球蛋白;B组联合使用狂犬病疫苗与抗狂犬病血清(马源);C组仅注射狂犬病疫苗,并采用小鼠中和试验对这三组成员在免疫后3、7、14、45天及1年时的中和抗体水平进行检测。结果表明：狂犬病疫苗与人狂犬病免疫球蛋白或抗狂犬病血清联合使用,可使体内更早出现抗狂犬病的中和抗体。注射人狂犬病免疫球蛋白后未发生临床副反应。     

The immunity and protective effects of antigen 85A and heat-shock protein X against progressive tuberculosis

The anti-tuberculosis vaccine, Mycobacterium bovis BCG, has been used worldwide, but its protective efficacy is variable against adult pulmonary tuberculosis. In this study, immune responses of antigen 85A (Ag85A) and heat-shock protein X (HspX) antigen of Mycobacterium tuberculosis were investigated during acute and stationary stage of infection in the murine aerosol TB challenge model and their protective effects were evaluated against progressive tuberculosis. A high level of Ag85A-specific IFN-γ production was induced from the early stage of the infection, whereas HspX-specific IFN-γ production was increased in the later stationary stage. As a subunit vaccine, Ag85A and HspX antigen vaccine induced high levels of IFN-γ, and a vaccine comprising both antigens induced the highest level of IFN-γ. At 30 days post-challenge, the Ag85A subunit vaccine was protective against M. tuberculosis challenge, but the HspX subunit vaccine was not. Interestingly, the HspX antigen vaccine induced significant protective efficacy at 90 days post-challenge. Moreover, the combined antigen vaccine induced the highest protective efficacy against M. tuberculosis challenge both at 30 days and 90 days post-challenge. These results suggest that the vaccine comprising Ag85A and HspX antigen which react in different stages of infection is highly protective against progressive tuberculosis.     

LLR株口服轮状病毒活疫苗在制品稳定性观察

对LLR株口服轮状病毒活疫苗生产中各阶段产物(在制品)放置于-20℃、2～8℃,进行稳定性观察,用细胞微量病变滴定法(CCID50)结合酶联免疫吸附试验(ELISA)检测其病毒感染滴度。结果显示,LLR株口服轮状病毒活疫苗单一收获物-20℃放置18个月,病毒滴度不低于5.50logCCID50/ml,原液-20℃放置18个月,病毒滴度不低于5.50logCCID50/ml。2～8℃存放49d,疫苗原液的病毒滴度不低于5.75logCCID50/ml,疫苗半成品病毒滴度不低于5.50logCCID50/ml。结果表明,LLR株口服轮状病毒活疫苗生产各阶段产物在-20℃及2～8℃存放,其稳定性良好。     

Investigations on the efficacy of monovalent Pseudomonas aeruginosa vaccine for oral administration in Pseudomonas aeruginosa experimental infection

Therapeutic efficacy of Pseudomonas aeruginosa vaccine for oral use (10(10) killed germs/ml), prepared from strain 4922, belonging to serotype XV, by Meitert-Meitert scheme, on 4 experimental models in mice (pneumonia, infected burn, septicaemia and urinary tract infection) was studied in comparison with monovalent Ps. aeruginosa vaccine serotype XV (10(9) killed germs/ml) for subcutaneous use and also with associated administration of the two vaccine variants. Mice immunization by using vaccine for oral use was performed by 0.5 ml vaccine per day, for 10 days and vaccine for subcutaneous use was administrated in a volume of 0.5 ml x 2, at 3 days interval. Mice immunization by using the two vaccine types, in association was concomitantly performed and in the same quantity as for separate immunization. In experimental pneumonia, Ps. aeruginosa vaccine for oral use protected mice in 35% of cases, those with infected burns were protected in 33.3% of cases, those with septicemia--in 96.6% of cases and those with urinary tract infection in 50% of cases. As compared to Ps. aeruginosa vaccine for subcutaneous use, the results obtained by vaccine for oral use are less favourable but associated administration of both vaccine variants led to superior results. Thus, in experimental pneumonia, it was obtained a surviving rate of 65% for animals immunized with both vaccine types, in comparison with 50% for animals immunized with vaccine for subcutaneous use only, and in Ps. aeruginosa infected burn, it was obtained a recovering rate of 79.1% for the animals immunized by using both vaccines, in comparison with 70.8% surviving for animals immunized with vaccine for subcutaneous use. In experimental septicaemia and urinary tract infection, combined use of both vaccine variants determined animals surviving and recovering in percents similar to those obtained by separate administration of vaccine for subcutaneous use (in septicemia--100% protection; in urinary tract infection--75% protection).     

Comparative characterisitic of changes in the adrenals against a background of immunization with viral and bacterial antigens]

The effect of alcoholic typhoid vaccine and of the cultural vaccine against the tickborne encephalitis on the adrenocortical secretion in guinea pigs was studied. Functional condition of the adrenal glands was assessed histochemically. Immunization was accompanied by increase in the activity of the adrenal cortex, the most pronounced the first 3 days. Comparative analysis showed that typhoid vaccine produced a more pronounced stree on the adrenal gland function.     

Swelling of the brain in mice caused by pertussis vaccine--its quantitative determination and the responsible factors in the vaccine

Intracerebral injection of vaccine into the mouse induced swelling of the brain. The swelling reached the maximum in the intensity by day 1 and persisted for several days. A method for quantitative determination of the brain-swelling activity of the vaccine was developed. A positive regression coefficient was found only between the brain-swelling and the lymphocytosis-promoting activities. Such activity was no longer shown with the vaccine heat-treated for 30 min at 80 C, but it was restored upon addition of the lymphocytosis-promoting factor (LPF) that caused no brain swelling by itself. The activity, therefore, was ascribed to cooperation of LPF and a certain heat-stable component other than endotoxin contained by pertussis vaccine.     

Effects of pertussis vaccine on the lipid metabolism of hamsters

Administration of pertussis vaccine to hamsters markedly affected their lipid metabolism. Four days after the administration of the vaccine a severe fatty liver was observed. Concomitantly, a rise in the serum levels of free fatty acids, triacylglycerols and ketone bodies was detected. It is suggested that an altered regulation of adipose tissue lipolysis might be at least partially responsible for the observed effects.     

浓缩狂犬病疫苗接种后不良反应与血清抗体水平分析

报导了≥２．５ＩＵ浓缩狂苗人体接种后的不良反应其反应率为１．３１％与以往未浓缩常规苗的反应率为０．７３％比较两者具有显著性差异（Ｘ２＝６．９４,Ｐ＜０．０１）,浓缩苗以注射１～３针时的不良反应多,临床表现以局部极痛、红肿、瘙痒、急性荨麻疹和过敏性休克等。但其血清抗体阳转率７天时为４０．０％以上,１４天时为１００％,而常规苗仅是４０．０％,抗体滴度浓缩苗第７天时达到有效保护水平（中和试验）。显示了其抗体产生早,水平高特点,关于如何减少浓缩狂苗不良反应问题,作者提出了几点建议     

Potentiation of the efficacy of murine L1210 leukemia vaccine by a novel immunostimulator 7-thia-8-oxoguanosine: Increased survival after immunization with vaccine plus 7-thia-8-oxoguanosine

Summary We have investigated the ability of a novel immunopotentiator, 7-thia-8-oxoguanosine (7T8OG) to increase the efficacy of a weakly immunogenic murine L1210 leukemia vaccine. The vaccine was prepared by irradiating L1210 leukemia cells in a cesium source with a total of 6000-R dose. DBA/2 mice were treated with 150 mg/kg 7T8OG and/or with vaccine consisting of 10⁷ irradiated cells. In combination therapy, mice first received the vaccine and then were injected with 75 mg/kg 7T8OG 2 h and 4 h after vaccination. One week after the last treatment all mice were inoculated with 10⁴ live leukemia cells intraperitoneally. Control, untreated mice (n = 66) injected with 10⁴ live leukemia cells had a mean survival time ± standard error of 10.5±0.2 days. Treating mice (n = 66) with one, two or three doses of 7T8OG administered i.p. 1 week apart did not increase survival (mean survival time = 10.7 days). Mice immunized with one, two or three doses of vaccine had 14.5±1.1, 45.4±6.2 and 68.3±10.6 days mean survival, respectively. 7T8OG-stimulated vaccination increased the survival dramatically. The best survival was noted when the mice were treated with 2× (vaccine + 7T8OG). Immunization of mice (n = 30) with this treatment regimen increased the mean survival to 156±10.0 days. Over 90% of mice that were treated this way had a cumulative survival time greater than 160 days. In contrast, only 12% of the mice immunized twice with the leukemia vaccine alone survived over 160 days. These results suggest a rationale for the use of this immuno-potentiator with various vaccines for a more effective immunization.     

Enhancing effects of the chemical adjuvant levamisole on the DNA vaccine pVIR‐P12A‐IL18‐3C

DNA‐based vaccination is an attractive alternative for overcoming the disadvantages of inactivated virus vaccines; however, DNA vaccines alone often generate only weak immune responses. In this study, the efficacy of LMS as a chemical adjuvant on a DNA vaccine (pVIR‐P12A‐IL18‐3C) encoding the P1‐2A and 3C genes of the FMDV and swine IL‐18, which provides protection against FMDV challenge, was tested. All test pigs were administered booster vaccinations 28 days after the initial inoculation, and were challenged with 1000 ID₅₀ FMDV O/NY00 20 days after the booster vaccination. Positive and negative control groups were inoculated with inactivated virus vaccine and PBS respectively. The DNA vaccine plus LMS induced greater humoral and cell‐mediated responses than the DNA vaccine alone, as evidenced by higher concentrations of neutralizing and specific anti‐FMDV antibodies, and by higher concentrations of T‐lymphocyte proliferation and IFN‐γ production, respectively. FMDV challenge revealed that the DNA vaccine plus LMS provided higher protection than the DNA vaccine alone. This study demonstrates that LMS may be useful as an adjuvant for improving the protective efficiency of DNA vaccination against FMDV in pigs.     

Persistence of an Escherichia coli-Shigella flexneri Hybrid in the Intestinal Tract of Macaca mulatta

A live oral vaccine prepared from an Escherichia coli-Shigella flexneri 4b hybrid was administered by gavage to Macaca mulatta. In the three main studies involving 160 monkeys, three doses were used, generally consisting of 5 x 10(9) to 60 x 10(9) cells per dose, with an interval between doses of 6, 7, or 14 days. Rectal swab cultures at the time of the last vaccine dose, and 14 to 58 days later, revealed that the hybrid persisted in the intestinal tract for at least 7 days in 16%, and for at least 21 days in 8%, of the monkeys. Our findings are comparable to those of Formal et al. for shedding of an E. coli-S. flexneri 2a hybrid. Protection studies with the E. coli-S. flexneri 4b hybrid are indicated.     

Cellular immune response to an engineered cell-based tumor vaccine at the vaccination site

The engineered expression of the immune co-stimulatory molecules CD80 and CD137L on the surface of a neuroblastoma cell line converts this tumor into a cell-based cancer vaccine. The mechanism by which this vaccine activates the immune system was investigated by capturing and analyzing immune cells responding to the vaccine cell line embedded in a collagen matrix and injected subcutaneously. The vaccine induced a significant increase in the number of activated CD62L(-) CCR7(-) CD49b(+) CD8 effector memory T cells captured in the matrix. Importantly, vaccine responsive cells could be detected in the vaccine matrix within a matter of days as demonstrated by IFN-gamma production. The substitution of unmodified tumor cells for the vaccine during serial vaccination resulted in a significant decrease in activated T cells present in the matrix, indicating that immune responses at the vaccine site are a dynamic process that must be propagated by continued co-stimulation.     

Modulation of humoral immune response through probiotic intake

Thirty healthy volunteers were randomised into three different treatment groups and consumed Lactobacillus GG, Lactococcus lactis or placebo (ethyl cellulose) for 7 days. On days 1, 3 and 5, an attenuated Salmonella typhi Ty21a oral vaccine was given to all subjects to mimic an enteropathogenic infection. All subjects responded well to the vaccine, but no significant differences were observed in numbers of IgA-, IgG- and IgM-secreting cells among the different groups. There was a trend towards a greater increase in specific IgA among the subjects receiving the vaccine in combination with Lactobacillus GG. Those receiving L. lactis with their vaccine evinced significantly higher CR3 receptor expression on neutrophils than those receiving either the placebo or Lactobacillus GG. These results indicate that probiotics may influence differently the immune response to oral S. typhi vaccine and that the immunomodulatory effect of probiotics is strain-dependent.     

Single immunization with MF59-adjuvanted inactivated whole-virion H7N9 influenza vaccine provides early protection against H7N9 virus challenge in mice

H7N9 influenza infection in humans would result in severe respiratory illness. Vaccination is the best way to prevent influenza virus. In this paper, we investigated the effect of early protection provided by inactivated whole-virion H7N9 influenza vaccine in a mouse model.Mice were immunized intramuscularly once with different doses of inactivated whole-virion H7N9 influenza vaccine alone or in combination with MF59 adjuvant. Specific IgM and IgG antibody titers in sera of mice were detected by ELISA 3, 5 and 7days after immunization. To evaluate the early protection provided by the vaccine, mice were challenged with lethal dose (40LD₅₀) of homologous virus 3, 5 and 7 days after immunization respectively. The survival rate and body weight change of mice during 21 days after challenge and the residual lung virus titer on 3rd day after challenge were determined. The results demonstrated that mice could obtain effective protection 3 days after immunization with the vaccine at a high dose, and 5–7 days after immunization even at a low dose. Thus early immune responses induced by inactivated whole-virion H7N9 vaccine could provide effective protection.     

Determination of the epinephrine-refractory hypoglycaemic activity of whole-cell pertussis vaccine in mice

A new assay method has been developed for the quantitative estimation of the inhibitory effect of pertussis vaccine on epinephrine-induced hyperglycaemia in mice. The statistical analysis of the assay was based on logarithm-transformed estimates of the blood glucose levels. The method was sufficiently sensitive to detect the activity of 0.004 millilitre of commercial combined diphtheria-tetanus-whole cell pertussis vaccine. The estimated common variance was as small as 0.0034 and the assay was highly reproducible. Among commercial vaccines there was a significant difference in activity. The activity of a stock pertussis vaccine was inactivated by 5 mM glutaraldehyde at 37 degrees C for 30 min, but resisted treatment with 40 mM formaldehyde at 37 degrees C for 5 days. The extent of inactivation with the chemicals was calculated by a parallel line assay as the activity relative to that of untreated control pertussis vaccine.     

Preventive properties of the blood sera from persons vaccinated with a Proteus vaccine made from soluble antigen complexes

In experiments of the passive protection of mice the protective properties of sera obtained from humans before and after their immunization with Proteus vaccine used as a monopreparation or in combination with staphylococcal toxoid and/or pyoimmunogen were studied. When introduced in a single subcutaneous injection, Proteus vaccine prepared from soluble antigenic complexes ensured an increase in the protective properties of sera. The second injection of the vaccine essentially enhanced the protective potency of the sera of the immunized donors. The therapeutic injection of Proteus vaccine ensured the essential increase of the protective properties of the sera. This increase could be experimentally detected within at least 25-30 days from the beginning of immunization. The immunization of volunteers with Proteus vaccine in combination with pyoimmunogen and adsorbed staphylococcal toxoid ensured the maximum increase of the protective properties of their sera.     

Studies on the Protection Test of Pertussis Vaccine. Immunization Period and Protectivity

In order to confirm the data reported in the previous papers, variously prepared pertussis vaccines were employed in the present investigation. Pertussis organisms grown either on a solid or in a liquid semisynthetic medium were treated by: (1) heating at 56 C for 30 min, (2) storage in 0.1% formalin at 37 C for 5 days, (3) storage in 0.1% formalin at 25 C for 5 days, and (4) simple addition of sodium ethyl-mercuri thiosalicylate (merthiolate) as a preservative. Freeze-dried vaccines were made from these preparations four and a half months later. Mice were immunized intraperitoneally and challenged intracerebrally with a virulent strain of Bordetella pertussis 10 or 17 days later. The data were analyzed statistically assuming the probit corresponding to the percentage of survivors at any dose be a linear function of the logarithms of the dose. The 50% effective doses (ED₅₀) and slopes of each vaccine were found to be uniform. More accurate estimates of ED₅₀ were obtained by employing a pooled slope in each experiment. From these ED₅₀ values, the relative potency was estimated by comparing the value of a vaccine to that of a dried merthiolate-vaccine. For vaccines derived from solid cultures, with an immunization period of 17 days, the relative potency of the vaccine heated at 56 C was 0.63 (95% fiducial limits=0.52 to 0.76); the value for the formalinized vaccine at 37 C was 0.40 (0.30 to 0.53) and one at 25 C was 0.51 (0.34 to 0.77). Vaccines derived from liquid cultures showed a relative potency of 20 to 50% less than that of corresponding vaccine derived from a solid culture. The potency obtained for the 17 day immunization period was usually higher than that for the 10 day period. Using the overall-pooled slope, an experimental design which will be appropriate for statistical analysis is discussed.     

The effect of tularemia vaccine on the radioresistance of white rats exposed to x-irradiation

A single epicutaneous vaccination of Wistar rats with tularemic live vaccine 15 days before X-irradiation with doses of 6.0, 8.0 and 2.0 + 6.0 Gy was shown to increase their radioresistance. With higher doses (up to 8.0 Gy) the effect of the vaccine was less pronounced.