scholarly journals IMMUNOLOGICAL AND CHEMICAL INVESTIGATIONS OF VACCINE VIRUS

1936 ◽  
Vol 63 (1) ◽  
pp. 69-94 ◽  
Author(s):  
Robert F. Parker ◽  
Thomas M. Rivers

Humoral antibodies and a certain degree of resistance to infection with vaccinia, probably not enduring, are produced in rabbits by the repeated injections of inactive formolized (0.3 per cent) elementary bodies of vaccinia and virus-free filtrates of dermal vaccine virus. Single injections of large amounts of elementary bodies are not as effective as similar amounts administered in small repeated doses. Drastic treatment (10 per cent formaldehyde or boiling for 2 hours) almost completely alters or destroys the antigenicity of elementary bodies. It appears that the production of precipitins and agglutinins does not parallel that of neutralizing antibodies and that the mere presence of such antibodies in the serum of a rabbit as the result of injections of inactive elementary bodies does not necessarily indicate that the animal possesses a great degree of resistance to infection with a potent vaccine virus. The fact that some neutralizing antibodies appeared in the sera of rabbits that had received injections of inactive elementary bodies can be interpreted as indicating that at least not all neutralizing antibodies for vaccine virus are the result of a reaction to an antigen produced by the host in consequence of a vaccinal infection. No evidence was obtained to show that elementary bodies inactivated by our methods (0.3 per cent formaldehyde) would serve as a suitable vaccine for the protection of human beings against smallpox.

1934 ◽  
Vol 60 (2) ◽  
pp. 211-238 ◽  
Author(s):  
Thomas M. Rivers ◽  
Francis F. Schwentker

Monkeys that have recovered from psittacosis pneumonia have an increased resistance to infection with the virus and possess neutralizing antibodies in their sera. Large amounts of active psittacosis virus can be introduced intravenously and intramuscularly into monkeys without the production of a serious infection such as pneumonia. Relatively small amounts of virus introduced intratracheally into monkeys usually lead to psittacosis pneumonia. Monkeys vaccinated intramuscularly with unattenuated psittacosis virus have an increased resistance to the active agent and possess neutralizing antibodies in their sera. The intramuscular introduction of active psittacosis virus in moderate amounts into human beings is relatively harmless, and repeated inoculations lead to the appearance of neutralizing antibodies in the sera of vaccinated individuals.


1896 ◽  
Vol 1 (3) ◽  
pp. 447-481 ◽  
Author(s):  
A. C. Abbott

The deductions that may be drawn from the results of these experiments are as follows: That the normal vital resistance of rabbits to infection by streptococcus pyogenes (erysipelatos) is markedly diminished through the influence of alcohol when given daily to the stage of acute intoxication. That a similar, though by no means so conspicuous, diminution of resistance to infection and intoxication by the bacillus coli communis also occurs in rabbits subjected to the same influences. And that, while in alcoholized rabbits inoculated in various ways with staphylococcus pyogenes aureus, individual instances of lowered resistance are observed, still it is impossible to say from these experiments that in general a marked difference is noticed between alcoholized and non-alcoholized animals as regards infection by this particular organism. It is interesting to note that the results of inoculation of alcoholized rabbits with the erysipelas coccus correspond in a way with clinical observations on human beings addicted to the excessive use of alcohol when infected by this organism. In the course of the work an effort was made to determine if, through the oxidation of alcohol in the tissues to acids of the corresponding chemical group, the increase of susceptibility could be referred to a diminution in the alkalinity of the blood as a result of the presence of such acids. The number of experiments thus far made on this point is too small to justify dogmatic statements, but from what we have gathered there is but little evidence in support of this view. Throughout these experiments, with few exceptions, it will be seen that the alcoholized animals not only showed the effects of the inoculations earlier than did the non-alcoholized rabbits, but in the case of the streptococcus inoculations the lesions produced (formation of miliary abscesses) were much more pronounced than are those that usually follow inoculation with this organism. With regard to the predisposing influence of the alcohol, one is constrained to believe that it is in most cases the result of structural alterations consequent upon its direct action on the tissues, though in a number of the animals no such alteration could be made out by macroscopic examination. I am inclined, however, to the belief, in the light of the work of Berkley and of Friedenwald, done under the direction of Prof. Welch, in the Pathological Laboratory of the Johns Hopkina University, that a closer study of the tissues of these animals would have revealed in all of them structural changes of such a nature as to indicate disturbances of important vital functions of sufficient gravity to fully account for the loss of normal resistance. The conspicuous influence of the alcohol on the gastric mucous membrane in many of these animals, with the consequent disturbance of nutrition, is undoubtedly the explanation of the marked loss in body weight that was observed in many of the animals employed in these experiments. In this light the susceptibility induced by alcohol to excess is somewhat analogous to that induced by starvation, where we see the resistance of animals to particular forms of infection very markedly diminished.


Author(s):  
Wei Wang ◽  
Esmeralda Alvarado-Facundo ◽  
Russell Vassell ◽  
Limone Collins ◽  
Rhonda E Colombo ◽  
...  

Abstract Background Low vaccine effectiveness against A(H3N2) influenza in seasons with little antigenic drift has been attributed to substitutions in hemagglutinin (HA) acquired during vaccine virus propagation in eggs. Clinical trials comparing recombinant HA vaccine (rHA) and cell-derived inactivated influenza vaccine (IIV) to egg-derived IIVs provide opportunities to assess how egg-adaptive substitutions influence HA immunogenicity. Methods Neutralization titers in pre- and postimmunization sera from 133 adults immunized with 1 of 3 types of influenza vaccines in a randomized, open-label trial during the 2018–2019 influenza season were measured against egg- and cell-derived A/Singapore/INFIMH-16-0019/2016-like and circulating A(H3N2) influenza viruses using HA pseudoviruses. Results All vaccines elicited neutralizing antibodies to all H3 vaccine antigens, but the rHA vaccine elicited the highest titers and seroconversion rates against all strains tested. Egg- and cell-derived IIVs elicited responses similar to each other. Preimmunization titers against H3 HA pseudoviruses containing egg-adaptive substitutions T160K and L194P were high, but lower against H3 HA pseudoviruses without those substitutions. All vaccines boosted neutralization titers against HA pseudoviruses with egg-adaptive substitutions, but poorly neutralized wild-type 2019–2020 A/Kansas/14/2017 (H3N2) HA pseudoviruses. Conclusion Egg- and cell-derived 2018–2019 season influenza vaccines elicited similar neutralization titers and response rates, indicating that the cell-derived vaccine did not improve immunogenicity against the A(H3N2) viruses. The higher responses after rHA vaccination may be due to its higher HA content. All vaccines boosted titers to HA with egg-adaptive substitutions, suggesting boosting from past antigens or better exposure of HA epitopes. Studies comparing immunogenicity and effectiveness of different influenza vaccines across many seasons are needed.


1939 ◽  
Vol 69 (6) ◽  
pp. 857-866 ◽  
Author(s):  
Thomas M. Rivers ◽  
S. M. Ward ◽  
R. D. Baird

Continued cultivation of vaccine virus in a medium consisting of minced chick embryo tissue and Tyrode's solution has resulted in a virus qualitatively changed to such an extent that considerable amounts of it can be injected intradermally into human beings without danger or inconvenience. Individuals who are vaccinated intradermally with the cultured virus should be revaccinated dermally six months to a year later with a potent calf lymph virus in order to obtain a satisfactory immunity to smallpox without being subjected to the dangers and inconvenience associated with primary vaccinations with calf lymph virus.


1915 ◽  
Vol 21 (6) ◽  
pp. 539-570 ◽  
Author(s):  
Hideyo Noguchi

Vaccine virus freed from all associated bacteria by means of suitable disinfecting agents can be propagated in a pure state in the testicles of rabbits and bulls. The virus cultivated in this manner is not only devoid of all bacteria, but appears capable of indefinite transfer from one animal to another. Sixty passages in rabbits of a pure strain have been made within one year. Several transfers from testicle to testicle are required to bring about accurate adaptation of the virus to the testicular parenchyma, so that continued propagation in this way can be certainly secured. During the first transfers from testicle to testicle the activity of the virus may be less than the original skin specimen from which the pure strain was derived; but as the transfers proceed the activity rises until, when the adaptation is complete, the activity of the testicular equals that of the skin strain. The multiplication of the virus within the testicle is maximum on the fourth or fifth day after inoculation; the quantity of virus remains about stationary until the eighth day, when diminution begins. At the expiration of five weeks no more virus could be detected in the testicle. The vaccinal processes in the skin, cornea, and testicle of rabbits are practically identical whether the virus employed for the inoculation has been the original skin strain or the pure testicular strain; and the skin lesions produced in the calf with the two strains are also identical. In conformity with the finding mentioned in the last paragraph it has been found that human beings react to the pure testicular strain of vaccine virus in an entirely typical manner. In the case both of original vaccination and revaccination the vaccinal effects cannot be distinguished from those arising from uncomplicated skin virus. Pure strains of testicular virus are readily produced, and once secured they may be propagated in a pure state by the method described in rabbits or bulls without difficulty and with economy. The pure strains thus obtained should supply an ideal form of virus for employment in the vaccination of human beings.


2019 ◽  
Vol 21 (95) ◽  
pp. 62-65
Author(s):  
L. P. Livoschenko ◽  
E. M. Livoschenko

Non-plastic diseases are a problem both in medical and veterinary practice. The most common diseases in poultry caused by oncogenic viruses include lymphoid leukemia (LL) and Marek's disease (MD). A vaccine has been developed for HM. On breeds and lines of birds with high resistance to neoplasm, the vaccine is much better. It is possible to solve this problem by increasing the specific and overall resistance, by creating genetically disease-resistant lines and crosses of the bird. However, this requires some knowledge about the mechanism of disease resistance, the interaction of the pathogen with the body, ways to increase resistance, its correction, sensitivity of lines and hybrids to pathogens of the most common diseases. This requires criteria or markers that are indicators of the body's immunocompetence. The studies were performed on chickens of Leghorn D4 line and Poltava clay P37. The level of antibodies to leukemia-sarcoma complex (VLSC) viruses was determined in the neutralization reaction by a conventional method. As a viral material, a 30% suspension of tumors obtained from infected chickens with Raus sarcoma virus was used. The article presents data on the influence of epizootic categories of poultry on the resistance of embryos to oncornaviruses. For research, the bird by status with respect to antibodies to oncoviruses was divided into four categories: A+ the presence of antibodies; A- the absence of antibodies; B+ the presence of the virus; B- no virus. When selecting a resistant bird for neoplasm, only two categories A-B- and A+ B- are theoretically relevant. The possibility of obtaining offspring with or without antibodies, depending on the status of this phenomenon in his parents, was established. According to the data obtained in 60.0% of cases, the bird, free from neutralizing antibodies against HRV, can be obtained by mating cocks and chickens free of these antibodies. However, the absence of antibodies from parents cannot guarantee such in their offspring (approximately 40.0% were with antibodies). It may be that some of the offspring of the antibody-free bird do not have genetic resistance to infection and react with antibody production when in contact with the virus. If the chickens and roosters had antibodies, their offspring were only free from them in 31.3% of cases. These data, however, indicate that resistance to infection is inherited from offspring and from parents resistant to natural infection with oncoviruses, which makes it more likely to obtain resistant offspring (P < 0.01). There is also a pattern of getting families free of counteracting factors: they are more likely to get from chickens and cocks that have no antibodies. However, not always the absence of antibodies in roosters and chickens guaranteed the absence of antibodies in their offspring.


2001 ◽  
Vol 82 (9) ◽  
pp. 2191-2197 ◽  
Author(s):  
Ad Vos ◽  
Andreas Neubert ◽  
Elke Pommerening ◽  
Thomas Müller ◽  
Leopold Döhner ◽  
...  

The immunogenic properties of an E1-deleted, human adenovirus type 5 (Ad5) vaccine virus with activity against rabies were examined in mice, foxes and dogs using different routes of administration. NMRI mice received 105·8, 105·3, 104·3, 103·3 and 102·3 TCID50 by peroral or intramuscular (i.m.) administration. Furthermore, six mice received 105·8 TCID50 intracerebrally (i.c.). The construct elicited marked seroconversion in mice after oral administration. Immunoreactivity in mice was even more pronounced i.m. and i.c. After direct oral administration (108·0 TCID50) in foxes, six of eight animals developed rabies virus-neutralizing antibodies (VNA). All foxes immunized by direct injection (107·7 TCID50) in the membrane of the jejunum were shown to seroconvert. Pre-existing immunity against canine adenovirus did not hinder the development of rabies VNA after oral application of the construct (108·0 TCID50). Fox cubs (24–29 days old) born from rabies-immune vixens were shown to develop very high levels of rabies VNA after i.m. administration (108·0 TCID50), indicating that the immunogenicity of the construct could surpass maternally transferred immunity. In dogs, the construct (108·0 TCID50) induced a very strong immune response after i.m. administration. However, no immune response was detectable in dogs after direct oral administration (108·3 TCID50) or after endoscopic deposition in the smaller intestine (108·0 TCID50). Hence, it must be concluded that the construct is not suitable for oral vaccination of dogs against rabies.


1999 ◽  
Vol 73 (10) ◽  
pp. 8435-8440 ◽  
Author(s):  
Ulf Dittmer ◽  
Brent Race ◽  
Kim J. Hasenkrug

ABSTRACT Vaccination of mice with a live attenuated vaccine virus induces potent protection against subsequent challenge with pathogenic Friend retroviral complex. The kinetic studies presented here demonstrate protection from acute splenomegaly as early as 1 week postvaccination. At this time point virus-specific cytotoxic T lymphocytes (CTL) were demonstrable in direct chromium release assays. However, during the first 2 weeks after vaccination protection was incomplete since the mice were not protected against establishment of low-level persistent infections in the spleen. By 3 weeks postvaccination the animals were protected against the establishment of persistent virus as well as acute splenomegaly. The timing of this complete protection correlated with the presence of both virus-neutralizing antibodies and primed CTL in the immunized mice. Within 3 days of virus challenge, vaccinated mice showed high levels of activated B cells and CD4+ and CD8+ T cells, indicating an efficient priming of all lymphocyte subsets. Despite very limited replication of the vaccine virus, the protective effect was long lived and was still present 6 months after immunization.


1917 ◽  
Vol 25 (4) ◽  
pp. 539-543 ◽  
Author(s):  
Simon Flexner ◽  
Harold L. Amoss

The virus of poliomyelitis contained within the spinal cord and medulla of human beings and monkeys withstands glycerolation for many years. The specimens tested had been kept for 4 and 6 years respectively in 50 per cent glycerol at refrigerator temperature. The symptoms and lesions caused by this virus are identical with those produced by that contained in the more recently collected spinal cord and medulla. The specimens had lost a part of their activity under the conditions described, necessitating larger and repeated doses to induce infection. Whether this difference is due merely to quantitative reduction in number of viable microorganisms or to qualitative alterations under the influence of the mildly antiseptic glycerol has not been determined. An ineffective inoculation of tissues containing the virus does not increase resistance, but rather diminishes it, so that a subsequent injection, inadequate in itself, may cause experimental poliomyelitis. This power of survival under adverse conditions may not be without significance in respect to the recrudescence of poliomyelitis in a given locality and after a lapse of years. Hitherto this phenomenon has been accounted for by assuming a fresh importation of a virus of pronounced pathogenic power. It is possible that the explanation in some instances resides in the renewed activity of specimens of the virus surviving from a previous epidemic, while in other instances a fresh introduction actually takes place from a remote focus of infection. The infectious nervous tissues employed in these experiments did not yield in culture streptococci or other ordinary bacteria.


1936 ◽  
Vol 63 (1) ◽  
pp. 33-41 ◽  
Author(s):  
Richard E. Shope

In the experiments presented, Virus myxomatosum was observed to produce only a localized fibromatous or myxomatous orchitis when injected into the testicles of cottontail rabbits. This type of disease was quite unlike the acute fatal illness which the virus caused in domestic rabbits. 10 serial passages of Virus myxomatosum through cottontail rabbits, covering a total elapsed time of 140 days, failed to alter its pathogenicity for domestic rabbits. Although it proved impossible to convert the myxoma virus into fibroma virus by serial passage in cottontail rabbits, it was found that these animals, recovered from myxoma, had a solid resistance to infection with the fibroma virus. Furthermore, their sera possessed neutralizing antibodies effective against the fibroma virus as well as Virus myxomatosum. A similar cross-immunological relationship was observed in the cases of domestic rabbits that had survived an attack of infectious myxoma.


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