The effect of certain types of novocaine block on conditioned food reflexes

Summary The influence of varlous types of novocaine block on conditioned food reflexes were studied. Paranephritic, spinal, and intraperitoneal introduction of novocaine and sovcaine was used. Depression of conditioned reflexes was revealed, but orlentating reaction was preserved. The degree of this depression and its duration were different in various methods of novocaine introduction. Depression was grestest in epidural introduction. Probably, this effect is connected with extinguishing of afferent impulses by novocaine.Presented by Active Member USSR Academy of Medical Sciences, Professor V. N. Chernigovsky     

A comparative immunogenicity-reactogenicity dose-response study of influenza vaccine

This study examined the immunogenic and reactogenic responses of influenza vaccine in 29 healthy nonallergic adults at three vaccine dosages: 0.5 mL, 0.1 mL, and 0.05 mL. After immunization a 7-day assessment of adverse reactions was made and serial serum hemagglutination-inhibition (HAI) antibody responses were measured during a 28-day period. The incidence of adverse reactions was significantly decreased in the group receiving 0.1 mL and 0.05 mL compared with the group receiving 0.5 mL of vaccine. After immunization with 0.1 mL or 0.05 mL vaccine increases in serum HAI antibody to A/Leningrad, A/Taiwan, and B/Ann Arbor influenza antigens were seen comparable to those observed after 0.5 mL. However the magnitude of these rises were lower and were directly correlated with the dose of vaccine. Since immunization of egg-sensitive allergic patients with influenza vaccine poses a risk of localized and systemic reactions, a common clinical practice is to prevent such reactions by vaccine dilution. Although the results of the present study suggest that vaccine dilution results in a decrease in adverse reactions, there is also the risk of decrease protective immunity with this procedure and therefore the practice should not be condoned.     

Anaphylaxis from yellow fever vaccine

BACKGROUND: There are very few reports of anaphylactic reactions to yellow fever (YF) vaccine in the literature, and these date from the 1940s. OBJECTIVE: We sought to estimate the rate of YF vaccine-related anaphylaxis. METHODS: All reports of adverse reactions to YF vaccine submitted to the Vaccine Adverse Event Reporting System between 1990 and 1997 were reviewed for those meeting criteria for probable or possible anaphylactic reactions. RESULTS: Of 243 reports submitted, 40 describe probable or possible anaphylactic reactions. In 22 of these 40, YF vaccine was the only vaccine administered. There were 5,236,820 doses of YF vaccine distributed in the United States during this period. By using all 40 cases, the rate of YF vaccine-related anaphylaxis would be 40 in 5, 236,820 or about 1 in 131,000. In 35 of the reports, information was provided on whether previous doses of YF vaccine had been given. In 34 of these 35, the reaction occurred after the first dose of YF vaccine, suggesting that vaccine constituents other than the viral proteins may have been the allergens. The vaccine is grown in chicken embryos and contains gelatin as a stabilizer. CONCLUSION: YF vaccine can cause anaphylactic reactions. Persons presenting for YF vaccine should be asked if they have had adverse reactions to previous doses of this or other vaccines and if they are allergic to eggs, chicken, or gelatin. Health care workers administering YF vaccine should be prepared to recognize and treat anaphylactic reactions should they occur.     

A/New Jersey/76 influenza vaccine trial in seronegative schoolchildren: Comparison of a subunit vaccine with a whole-virus vaccine

Summary In the present vaccination trial, 202 seronegative schoolchildren comprising both sexes and aged 11 to 12 years were vaccinated i.m. in the upper arm with either the subunit vaccine at a dosage of 600 CCA or 200 CCA or with a whole-virus vaccine at a dosage of 200 CCA, using the double-blind procedure. Both vaccines were prepared from the strain A/New Jersey/76 (x 5 3a-recombinant). The vaccination was followed four weeks later by a booster injection. In tests of local and systemic reactogenicity, it was found that at both dosages the subunit vaccine caused a low frequency of minor adverse reactions. The whole-virus vaccine was marked by a significantly higher rate of adverse reactions, whether of the local or systemic variety. The whole-virus vaccine had, however, a higher immunogenicity than the subunit vaccine, and due to the relatively high rate of adverse reactions it causes, it is not recommended for the vaccination of seronegative children. Because of its low reactogenicity, the subunit vaccine can be given at higher dosage, and it is a matter for consideration whether a better antibody response might not result from two booster injections.     

Immunological safety and sensitizing effect of an MB-7-based vaccine against hepatitis A

The influence of a vaccine based on the MB-7 strain of hepatitis A virus (VP-MB-7) designed at the "Vector" Center of Virology and Biotechnology was studied. VP-MB-7 was found to provoke no allergic response and to have an activating effect on the specific and non-specific responses of cell and humoral immunity similar to those evoked by hepatitis A vaccine "Hep-A-in Vac".     

Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID-19 vaccines: A systematic review and meta-analysis

For persons with immediate allergic reactions to mRNA COVID-19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all-severity immediate allergic reactions upon re-vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception-Oct 4, 2021) for studies addressing immediate (≤4 h post-vaccination) all-severity allergic reactions to 2nd mRNA COVID-19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta-analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS-2 assessed risk of bias. Among 20 studies of mRNA COVID-19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re-vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01–0.52) and specificity 0.97 (95%CrI 0.9–1). PEG test sensitivity was 0.02 (95%CrI 0.00–0.07) and specificity 0.99 (95%CrI 0.96–1). PS test sensitivity was 0.03 (95%CrI 0.00–0.0.11) and specificity 0.97 (95%CrI 0.91–1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00–0.08) and specificity was 0.98 (95%CrI 0.95–1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all-severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID-19 vaccines. mRNA COVID-19 vaccine or excipient ST has limited risk assessment utility.     

Human hypersensitivity to a sham vaccine prepared from mosquito-cell culture fluids

A sham vaccine, prepared with the C6/36 cell line derived from larval Aedes albopictus mosquitoes, was skin tested on 12 volunteers. Although no reactions were observed after prick tests, three immediate reactions did occur after intradermal tests. Subcutaneous administration of the C6/36 sham vaccine was initially performed on the nine subjects who did not demonstrate immediate reactions. Five of these subjects developed delayed reactions at the site of the intradermal test within 12 hr after inoculation. A Prausnitz-Küstner test was performed on the back of one unsensitized subject by use of both unheated and heated sera from three subjects who had immediate skin reactions, three who demonstrated a delayed reaction, and one who had a negative skin response. In the Prausnitz-Küstner test, immediate skin reactions were observed with all seven unheated sera but with none of the heated serum aliquots. The determination that skin reactivity was associated with a heat-labile serum factor suggested the mechanism was IgE-mediated. Under close surveillance, the C6/36 sham vaccine was administered subcutaneously to one volunteer who had previously demonstrated an immediate response. This subject developed an anaphylactic reaction characterized by hives at the site and more distantly from the site of the subcutaneous inoculation. Hypersensitivity to A. albopictus larval antigens is common and precludes the use of C6/36 cell culture as a substrate for viral vaccines.     

Preservative-free influenza vaccine

OBJECTIVE: To investigate the immunogenicity of and tolerance towards the preservative-free inactivated influenza vaccine Begrivac. METHODS: In this prospective, single-centre, non-controlled study, efficacy was evaluated by the change in influenza antibody titre from baseline to 21 days following vaccination. The safety variables included post-injection reactions and adverse events. Blood samples were taken on day 21 and the antibody titre assayed by haemagglutination inhibition test. RESULTS: All three of the European efficacy requirements for influenza vaccines are satisfied by the new preservative-free vaccine described in this report. The mean geometric increase in titre and the proportion of vaccination responders were greater in patients of the adult group than in the elderly. Thus for strain A/Beijing/262/95 66% of subjects seroconverted and 28% showed a significant increase in antibody titre (total 94%), compared to a total of 45 patients (76%) in the elderly group. For strain A/Sydney/5/97 the corresponding figures were total 55 (90%) adult and 47 (80%) elderly, and for B/Beijing/184/93 46 (75%) adult and 31 (53%) elderly. Sixty four subjects (53%) reported adverse events, mainly local reactions at the injection site such as pain, erythema and induration, and systemic reactions such as headache and fatigue. CONCLUSIONS: The absence of preservative in this novel vaccine preparation does not have any detectable impact on its efficacy or safety and tolerability profile.     

Acellular pertussis vaccine in adults: Adverse reactions and immune response

An acellular pertussis vaccine JNIH-6 containing pertussis toxin and filamentous hemagglutinin was evaluated in adult volunteers with regard to adverse reactions and antibody response. Adverse reactions were few and mild. A late onset local reaction was seen in 22 of the 47 vaccinees (47 %) as compared to none of the 20 subjects receiving a placebo, the carrier solution of aluminium phosphate of the vaccine. The reaction, which manifested itself on the 6th to 8th day after vaccination, consisted in all cases of an induration and/or swelling considered insignificant by the majority of the subjects. The reaction was only found in vaccinees receiving a first dose of vaccine and was independent of the prevaccination antitoxin level. The vaccine induced a highly satisfactory antibody response to both filamentous hemagglutinin and pertussis toxin.     

Immunogenicity and safety of a new inactivated hepatitis a vaccine in a comparative study

A multicentre, controlled, randomised, open, comparative trial including 839 healthy adult volunteers was carried out in order to compare the immunogenicity and reactogenicity of two vaccines against hepatitis A virus (HAV) during primary immunization and after booster injection. The first vaccine was produced by Pasteur Mérieux (PM), and the second vaccine by Smith-Kline Beecham (SKB). The vaccination schedule consisted of 2 doses (months 0, 6) for PM and 3 doses (months 0, 1, and 6) for SKB. Two weeks after the first dose, the seroconversion rates among initially HAV seronegative subjects (n = 608) were 93.4% and 76.1% for the PM and SKB vaccines, respectively, the corresponding geometric mean titres (GMTs) were 59.0 mlU/ml versus 30.8 mlU/ml (modified RIA HAVAB assay, Abbott Laboratories). Two months after the beginning of immunization (one dose versus two doses) the GMTs were 138.4 and 161.6 mlU/ml, respectively. At month 7, the seroconversion rates were 100% for both vaccines, and the GMTs were 4, 189 and 3, 163 mlU/ml, respectively. After the first dose of vaccine, 24.6% and 19.6% of the PM and SKB vaccinees reported local reactions. The rates for systemic reactions were 27.2% and 25.0%, respectively. Lower rates for local and systemic reactions were seen after booster injections and statistical differences were not observed between the two vaccines. The study also demonstrated that vaccination was as well tolerated in subjects with anti-HAV antibodies as in HAV seronegative subjects. Logistic regression analysis revealed a significant vaccine effect on seroconversion rates only at week 2 (P<10^?4). The same conclusions were drawn from the analysis of GMT by multivariate regression. When both times (week 2 and week 8) were analysed together, a statistically significant effect of interaction between time and vaccine was observed, indicating that the kinetics of antibody responses were different. © 1995 Wiley-Liss, Inc.     

Properties of rabies vaccine freed of neuroallergenic factor from brain tissue

Fixed rabies virus in the form of infected sheep brain suspension was freed from approx. 80% of ballast proteins, inactivated by beta-propiolactone and lyophilized. The vaccine thus obtained was devoid of neuroallergenicity when tested on guinea pigs and was highly antigenic and immunogenic. The vaccine caused no generalized reactions in volunteers; local reactions were weak and of short duration. Antibody formation was intensive in all volunteers.     

Allergic reactions to Japanese encephalitis vaccine

The JEV widely is used in Asian countries each year and is an important vaccine for travelers to the East from other parts of the world. JE virus is a zoonotic disease with natural reservoirs and cannot be eliminated. Although a declining incidence of JE has been observed in Asia because of reduced transmission by agricultural approaches and vaccination, the most important control measure now, and in the future, is vaccination of humans against JE. The inactivated vaccine, produced from infected mouse-brain-derived tissue, is the only commercially available vaccine. There are several concerns with the use of this vaccine. It is expensive, requires two or three doses to achieve protective efficacy, and, in practice, requires further booster doses to maintain immunity. The apparent increase in allergic reactions in the first part of the 1990s has set focus on the safety of the JEV. A cheap, live attenuated SA 14-14-2 vaccine is used almost exclusively in China and parts of Korea, but there have been no trials of SA 14-14-2 vaccine outside JE endemic countries. The vaccine seems to be highly efficient, and few adverse events have been observed; however, PHK cells are used for the production of this vaccine, and these cells are not approved by the WHO. A satisfactory cell substrate is needed. A committee under the WHO has proposed that for the live JEV, there should be validity of the assays for retrovirus when applied to PHK cell substrate and validity of the mouse assays for neurovirulence. Further information should be reviewed on the long-term follow-up of recipients of the vaccine. Several new types of vaccines have reached the phase of clinical trials; however, studies remain to be completed. Until a new vaccine is available, the priority of surveillance of adverse events and the continuous reporting of such events to the users of the vaccines must be of importance. This fact is highlighted by the possibility of the varying frequency of adverse events with different batches over the years. The WHO offers information and recommendations for vaccines in the EPI and issues a series of updated papers on other vaccines that are of international public health importance (eg, JEV). The development of alternative efficient, safe, and appropriately priced JEVs is recommended, as is intensified surveillance of adverse events. Prospective vaccine studies of safety may be limited because of sample size and because rare adverse events may not be detected. Several new initiatives have been taken to improve surveillance of adverse events to vaccines within the past 10 years. In Japan, there is an increasing awareness of the importance of efforts taken to improve vaccine safety, and surveillance of adverse events and possibilities of compensation for vaccine-related injuries are in place. In Vietnam, a database to detect adverse events after vaccination has been established; the project involves active visits to data collectors at the vaccination sites. Comparative studies of adverse events, such as one recent study from Japan and the United States, are important for the evaluation of the reporting systems. The reporting rate for JEV adverse events from Japan was approximately one order of magnitude lower than that in the United States. Japan had strict predefined reporting criteria and time limits for observations. If time limits for the observation are too strict (eg, defining a possible neurologic reaction to occur within 1 week after vaccination), later reactions will not be included (eg, if ADEM is elicited by a vaccine, the symptoms cannot be expected to occur until weeks after the vaccination). The passive surveillance systems have limitations with an underreporting of adverse events, depending on clinical seriousness, temporal proximity to vaccination, awareness of healthcare workers, and tradition of reporting particular events. In developed countries, surveillance of adverse events is formalized, although not necessarily optimal. An increase in reporting would be expected when the reporting of adverse events is mandatory. Reports have been sent to VAERS, the Vaccine Safety Datalink Project, and the European Union Pharmacovigilance System. A Brighton collaboration has been implemented to enhance comparability of vaccine safety data. Public health authorities in specific countries, such as the CDC in the United States and the National Advisory Committee in Canada, regularly have published information on the JE situation in Asia and the preventive measures to be taken, including information on the vaccines and adverse reactions. The conventional recommendation is that travelers should be vaccinated if they will spend more than 1 month in a JE endemic area or in areas with epidemic transmission with even shorter periods. Although the risk for JE for short-term travelers is considered small (1 case per 1 million travelers per year), sporadic cases, including deaths, have been reported among tourists traveling to endemic areas. Risk for travelers in rural districts in the season of risk is considerably higher (range, 1 case per 5000 travelers to 1 case per 20,000 travelers per week). Doctors who advise travelers should be updated on the latest JE occurrences in Asia. Updates on the JE situation can be found on bulletins at http://www.promedmail.org or are available from the WHO or CDC. The allergic reactions primarily described after vaccination with the inactivated mouse-brain-derived JEV have been observed in several countries during the 1900s. Allergic reactions, including the mucocutaneous and neurologic reactions reported after JE vaccination, may vary in frequency, and these reactions should be evaluated meticulously yearly. This step enables recommendations, including information on possible side effects, to be given in an optimal way.     

Specific immune response to vaccination with an inactivated flue vaccine depending on prevaccine status and age of the person vaccinated

Specific antibody immune response to vaccination with commercial inactivated trivalent vaccine A(H1N1) + A(H3N2) + B (IgA, IgG, IgG, subclasses G1, G3, G4, and accumulation of antiCD8) was studied in subjects aged 20-95 years. The initial immune status before vaccination is significant for a positive immune response to the vaccine. Subjects responding to immunization by an increment in specific IgG had a much lower prevaccination level of these antibodies than subjects without these Ig conversion. Antibody immune response to vaccination depended on patient's age. All vaccinees aged 20-25 years developed an increment in IgG to at least one of influenza antigens used. Specific postvaccinal immune response to inactivated influenza vaccine included accumulation of G1, G3, and A antibodies, but not G4 or E antibodies. This latter fact suggests the absence of sensitizing effect of vaccination. In elderly subjects an increment in G1, G3, and A antibodies may not involve an increase in the total level of IgG. In part of elderly subjects secretion of specific antibodies was observed in the presence of increased concentration of antilymphocytic antibodies (antiCD8), indicating a possibility of autoimmune reactions in subjects of this age after injection of inactivated influenza vaccine.     

The influence of novocaine on pessimal inhibition in various links of the reflex arc

Summary The mechanism of the action of novocaine was studied experimentally. It was demonstrated that in resorptive action of novocaine it increases the pessimal inhibition in the reflex centers of the spinal cord the vegetative ganglia and the neuro-muscular apparatus. Experiments were performed according to the teaching of Vedensky on the functional mobility of the excitable formations.Presented by Active Member AMS USSR V. V. Zakusov     

Characteristics of the immune response in children multiply inoculated with an inactivated influenza vaccine

The observations involved 1082 children ranging in ages from 11 to 14 years who had been annually given from one to four injections of inactivated chromatographic influenza vaccine. An additional group consisted of 242 children who after three years of vaccination with the inactivated vaccine were given a live influenza vaccine type A (H1N1) and A (H3N2) for children. The studies showed that the highest immunological effect in children was achieved after two years of vaccination with the inactivated influenza vaccine. No positive effect on the immune response in children was demonstrated by the addition of a live vaccine into the immunization schedule against the background of multiple immunizations with the inactivated one. Different types of responses in children to immunization against influenza were observed.     

Reactogenicity and immunogenicity of a surface-antigen-adsorbed influenza virus vaccine in children.

An influenza virus vaccine containing the purified surface haemagglutinin and neuraminidase antigens of A/Victoria/75 and B/Hong Kong/73 viruses adsorbed to an aluminium hydroxide gel was assessed for reactogenicity and immunogenicity in children aged 4 to 11 years, since there is no influenza virus vaccine available for this age group. Significant serum haemagglutination-inhibiting antibody responses to the A/Victoria/75 and B/Hong Kong/73 haemagglutinin antigens present in the vaccine were observed in 47% and 35%, respectively, of the children vaccinated, with a single dose. The vaccine induced no significant local or systemic reactions.     

The absence of differences in cellular immunity in elderly individuals with and without delayed local cutaneous reactions to influenza vaccine.

Two groups of elderly subjects who received bivalent influenza virus vaccine were identified. Those in Group I manifested marked local reactions, suggestive of delayed hypersensitivity reactions, whereas those in Group II, matched with Group I for vaccine preparation, had no cutaneous reactions. In vitro assays of immune function were performed on pairs of subjects from the two groups and included serum immunoglobulin and complement levels, antibody response to vaccine, lymphocyte transformation to mitogens (phytohemagglutinin, pokeweed mitogen and concanavalin A) and antigens (streptokinase-streptodornase, influenza virus vaccine antigens and multiple mixed lymphocytes), and polymorphonuclear leukocyte chemotactic responsiveness. There was no demonstrable correlation between delayed local cutaneous reaction and preservation of in vitro cell-mediated immune function in these elderly individuals.     

IL-12对小鼠肥大细胞瘤基因疫苗的免疫学作用

目的 研究小鼠肥大细胞瘤P815基因疫苗和鼠IL-12对该疫苗的免疫学作用。方法 将小鼠肥大细胞瘤P815特异抗原基因P1A克隆到真核表达质粒pCI-neo中；用P815细胞对DBA/2小鼠右腹侧皮下注射，构建P815小鼠肿瘤模型；以重组基因疫苗单独或与鼠IL-12真核表达质粒一起肌肉注射，观察肿瘤的消长，特异细胞毒T淋巴细胞激活和抗全的生成情况。结果 重组基因疫苗在体外有很好的表达，注射后CTL的杀伤效率为40%，IL-12共注射的CTI，杀伤效率达到60%，免疫后，30%小鼠的肿瘤出现消退；同IL-12共注射则有50%的小鼠的肿瘤出现消退，2种情况下都不能检测到任何特异抗体的产生。结论 重组P1A肿瘤疫苗能有效激活机体的肿瘤特异免疫应答；基因疫苗对小鼠P815肿瘤的治疗作用主要归因于细胞免疫；IL-12有增强这种免疫应答的作用。     

狂犬病疫苗免疫接种后抗体水平分析

目的了解惠州市犬咬伤人群全程接种疫苗后机体受到保护的情况,为狂犬病疫苗预防接种工作提供依据。方法采用酶联免疫法检测抗狂犬病毒抗体。结果狂犬病疫苗暴露后人群不同年龄组差异有统计学意义（χ2=33.78,P〈0.05）,随着年龄的增大,接种狂犬疫苗后抗体阳性率呈下降趋势,不同性别的抗体水平差异无统计学意义。结论全程接种狂犬病疫苗后产生较为良好的免疫效果。     

An immunotherapeutic vaccine for multibacillary leprosy

On January 30, 1998, a vaccine for leprosy based on Mycobacterium w (the code word under which this species hitherto unspecified was investigated) was launched for public use for therapeutic purposes. The vaccine has completed phase III immunotherapeutic trials as an adjunct to chemotherapy in urban and rural leprosy control centres and has received the authorization from the Drugs Controller of India for industrial manufacture. It will be made available by M/s Cadila Pharmaceuticals, Ahmedabad. As an adjunct to chemotherapy, the vaccine expediates bacterial clearance and accelerates clinical regression of lesions. It shortens significantly the period for release from treatment (RFT) of patients. It is effective in inducing a fall of bacterial index (BI) in multibacillary patients who are either nonresponders or slow responders to the standard multidrug therapy and who have persistent BI over long periods. An additional benefit of immunization with this vaccine is the conversion of >60% of LL, 71% of BL and 100% of BB patients from lepromin negativity to lepromin positivity status. A significant number of vaccinated patients showed histopathological upgrading and eventually attainment of a state of nonspecific infiltration without dermal granulomas. The vaccine was well tolerated and the incidence of Type 2 reactions and their severity was less in combined immuno cum chemotherapy group than in the group receiving only chemotherapy. This review describes the nature of the vaccine and the way it was developed.