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Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen., Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study, we evaluated the durability of protection from intranasal (i.n.) pertussis vaccines in mice. Mice that convalesced from B. pertussis infection served as a control group. Mice were immunized with a mock vaccine (phosphate-buffered saline [PBS]), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particles (IRI-1501). We utilized two study designs: short term (challenged 35 days after priming vaccination) and long term (challenged 6 months after boost). The short-term study demonstrated that immunization with i.n. vaccine candidates decreased the bacterial burden in the respiratory tract, reduced markers of inflammation, and induced significant serum and lung antibody titers. In the long-term study, protection from bacterial challenge mirrored the results observed in the short-term challenge study. Immunization with pertussis antigens alone was surprisingly protective in both models; however, the alum and IRI-1501 adjuvants induced significant B. pertussis-specific IgG antibodies in both the serum and lung and increased numbers of anti-B. pertussis IgG-secreting plasma cells in the bone marrow. Our data indicate that humoral responses induced by the i.n. vaccines correlated with protection, suggesting that long-term antibody responses can be protective.

Background: To evaluate the persistence of antibody for 10 years, and investigate the effect of one or two booster doses with Kanghua human diploid cells rabies vaccine (HDCV) in China. Methods: Participants were re-recruited at year 10 post the primary phase 3 clinical study. Some of them in Kanghua HDCV group who had been boosted one dose at year 8, received one more dose at this boosted study. Participants who never boosted were randomly assigned to boost 1 or 2 doses of Kanghua HDCV. Blood samples were collected at day 0, 1, 3, 7, and 14. Safety was evaluated from day 0–14. Results: At year 10 after primary vaccination, the seroconversion rates of neutralizing antibody were 98.28–100% in Kanghua and Pasteur groups. After booster, the seroconversion rate in each group reached to 100% from day 7 to day 14. GMCs were similar in the groups with the same booster doses, and two doses of booster induced higher levels of antibody. The reported rates of solicited local and systemic adverse reaction were low, and no serious adverse events were found through the boosted study. Conclusion: 5 doses of Kanghua HDCV maintained long-term immunity at least 10 years. One or two doses of booster, rapidly triggered 100% protection against rabies virus. Trial registration: ClinicalTrials.gov: NCT03774628

Immunotherapy has gained great momentum with chimeric antigen receptor T cell (CAR-T) therapy, in which patient’s T lymphocytes are genetically manipulated to recognize tumor-specific antigens increasing tumor elimination efficiency. In the last years, CAR-T cell immunotherapy for hematological malignancies achieved a great response rate on patients and is a very promising therapy for several other malignancies. Each new CAR design requires a preclinical proof-of-concept experiment using immunodeficient mouse models. The absence of a functional immune system in these mice makes them simple and suitable to be mathematically modeled. In this work, we developed a three population mathematical model to describe tumor response to CAR-T cell immunotherapy in immunodeficient mouse models, encompassing interactions between a non-solid tumor and CAR-T cells (effector and long-term memory). We account for several phenomena, such as tumor-induced immunosuppression, memory pool formation, and conversion of memory into effector CAR-T cells in the presence of new tumor cells. Individual donor and tumor specificities were considered as uncertainties in the model parameters. Our model is able to reproduce several CAR-T cell immunotherapy scenarios, with different CAR receptors and tumor targets reported in the literature. We found that therapy effectiveness mostly depends on some specific parameters such as the differentiation of effector to memory CAR-T cells, CAR-T cytotoxic capacity, tumor growth rate, and tumor-induced immunosuppression. In summary, our model can contribute to reduce and optimize the number of in vivo experiments with in silico tests to select specific scenarios that could be tested in experimental research. Such in silico laboratory was made available in a Shiny R-based platform called CARTmath. It is an open-source, easy to run simulator, available at github.com/tmglncc/CARTmath or directly on the webpage cartmath.lncc.br, containing this manuscript results as examples and documentation. The developed model, together with the CARTmath platform, provides potential use for assessing different CAR-T cell immunotherapy protocols and associated efficacy, becoming an accessory towards in silico trials.

To the Editor The COVID-19 pandemic has been consistently on the rise across the globe. The recovered patients getting long-term sequelae, especially lung fibrosis and residual neurological deficits, is an area of concern. Another extremely important conundrum is the risk of re-infection. It has been recently documented from Hong Kong and puts an unpleasant question mark on long term immunity, sampling technique standardization, viral mutation and efficacy of herd immunity. There are definitions for COVID -19 infection and its severity, but unfortunately none for re-infection.

Whether T cells join the immune system9s fight against SARS-CoV-2, the virus that causes COVID-19, has been unclear. Two new studies have identified T cells that react to the virus in patients who had COVID-19 or were recovering from it. Both studies detected helper T cells, which orchestrate antiviral responses of other immune cells, and one of the studies also found killer T cells that eliminate virally infected cells. Both studies also discovered helper T cells that target the virus in blood samples from people who had never been infected. These people likely had the cells because they had been infected by similar coronaviruses that cause colds. The results suggest the virus induces a strong T cell response in patients, but they do not indicate whether people who have recovered from COVID-19 are immune to the virus.

SARS-CoV-2, the virus that causes COVID-19, has been unclear Now, two studies reveal that infected people harbor T cells that target the virus—and may help them recover Both studies also found that some people never infected with SARS-CoV-2 have these cellular defenses, most likely because they were previously infected with other coronaviruses “This is encouraging data,” says virologist Angela Rasmussen of Columbia University Although the studies don’t clarify whether people who clear a SARS-CoV-2 infection can ward off the virus in the future, both identified strong T cell responses to it, which “bodes well for the development of long-term protective immunity,” Rasmussen says The findings could also help researchers create better vaccines

Background Gam-COVID-Vac (SPUTNIK V) has been granted emergency use authorization in 70 nations and has been administered to millions worldwide. However, there are very few peer-reviewed studies describing its effects. Independent reports regarding safety and effectiveness could accelerate the final approval by the WHO. We aimed to study the long-term humoral immune response in naive and previously infected volunteers who received SPUTNIK V. Methods Humoral immune responses, assayed by anti-SARS-CoV-2-spike-RBD IgG ELISA and neutralization assays, were measured in 602 healthcare workers at 0, 14, 28, 60 and 180 days after receiving SPUTNIK V between December 2020 and July 2021 in Tucuman, Argentina. Findings Seroconversion was detected in 97% of individuals after 28 days post-vaccination (dpv) (N = 405). Anti-RBD titers began to decrease after 60 dpv (N = 328), but remained detectable in 94% at 90 dpv (N = 224). At 180 dpv, anti-RDB titers persisted in 31% (N = 146). Previous infection triggered an increased immune response to the first dose and increased neutralization activity against variants of concern (VOC). Second doses in previously infected individuals further increased titers, even 90 dpv (N = 75). Basal antibody titers had more influence on post-vaccination anti-RBD responses than the time elapsed between diagnosis and vaccination (N = 274). Interpretation Data presented herein provides essential knowledge regarding the kinetics of antibodies induced by SPUTNIK V up to six months after immunization, and suggests that when considering one-dose vaccination policies for individuals with previous SARS-CoV-2 infection, serological studies to determine basal titers may be important, independent of when diagnosis occurred. Funding Tucuman Public Health System (SIPROSA), Argentinean National Research Council (CONICET), National University of Tucuman (UNT).

Background: Pediatric patients with rheumatic diseases (RD) are at increased risk of infections. Vaccines have been proved to be very effective to prevent them. Nevertheless the long-term immunity after vaccination remains quite unknown in this group. Objectives: To comapre the long term seroprotecction in pediatric patients with rheumatic diseases who recieved measles, rubella, mumps, tetanus, diphteria, hepatitis B, hib and meningoccocus C vaccination acording to the routine immunization schedule in Spain, and healthy children. Methods: We designed a cross-sectional study including consecutive pediatric patients with RD who attended the rheumatology clinic and healthy children older than 10 y.o. The administered vaccines, treatment and pathology of each patient will be recorded. Their antibodies titters against each antigen were quantified and compared to healthy children. Results: 60 patients (median age 13 y.o IQR 10.2-12-7) and 15 healthy children (mean age 11.3 y.o. IQR 11.3-12.7) were included. In the patients group 62% were female, and 35% in healthy. Diagnosis: 85% Idiopathic juvenile arthritis, 18% Lupus or juvenile dermatomiositis. 46% had received biologic treatment sometime. Seroprotection rate was (patient vs control): measles 85%% vs 81%%, rubeola 78.8% vs 73.3%, parotiditis 84.7% vs 66.7%; VHB 27.% vs 10.5%, diphteria 89.5% vs 81%, tetanos 64.9% vs 61.1%. Hib 42% vs 53%, pneumococo 92.4% vs 100%, meningococcus C 12% vs 11%. p>0.05 Conclusion: No statistical differences were detected, althought the scarce number of control subjects might have infuenced this result. There is a tendence towards a lower antibody persistence anti-Hib in patients compared to healthy children. The response to life virus vaccine and tetanus seem to be as good as in healthy chidren. Disclosure of Interests: : Laura Fernandez Silveira: None declared, M.J Gimenez: None declared, E Andreu-Alapont: None declared, Patricia Falomir-Salcedo: None declared, E Serrano-Poveda: None declared, M.I. Gonzalez-Fernandez: None declared, B Lopez-Montesinos: None declared, Inmaculada Calvo Grant/research support from: received research grants from Pfizer, Roche, Novartis, Clementia, Sanofi, MSD, BMS and GSK, Consultant for: Advisory boards: Novartis, AbbVie, Speakers bureau: AbbVie, Roche, Novartis, SOBI

Background: Amongst the different modalities for the treatment of warts, not a single modality is fully effective. While treating warts, the possibility of spontaneous regression must also be kept in mind. The aim of treating warts is to induce long term immunity without recurrences. To study the efficacy and safety of intralesional bleomycin for the treatment of twenty patients with periungual and palmoplantar warts.Methods: We conducted a prospective study of twenty patients of resistant periungual and palmoplantar warts between the age group of 15-50 years. Three injections of bleomycin were given at an interval of 2 weeks for a maximum of 3 injections (or less if the resolution occurred earlier).Results: After three sessions, complete clearance of palmoplantar warts was 71.42% and that of periungual warts was 90.90%. lesions were seen in 82% patients and incomplete resolution was seen in 15% patients. Bleomycin has antibacterial, antiviral and cytotoxic activity. Commonest side effect after bleomycin injection was pain seen in 40% (8) patients followed by pigmentary change and Raynauds phenomenon seen in 5% (1) patient each.Conclusions: Bleomycin is an effective and promising treatment of recalcitrant warts especially in palmoplantar and periungual.

International audience; Degradation mechanisms accelerated by harsh conditions (high temperature, electrical stress) can affect circuit performances. Submitted to electromagnetic interferences, aged components can become more susceptible, which stirs up questions about the safety level of the final application. Unfortunately, the impact of circuit aging on its susceptibility level remains under evaluated and is not taken into account at circuit design level. This paper presents a first attempt of a modeling methodology aiming at predicting the impact of circuit aging on the susceptibility to electromagnetic interferences. This methodology is applied to model and explain the measured variations of the susceptibility level of phase-locked loop after an accelerated-life test.

Subclinical or asymptomatic infection is documented in individuals living in endemic areas for leishmaniasis suggesting that the development of an appropriate immune response can control parasite replication and maintain tissue integrity. A low morbidity indicates that intrinsic factors could favor resistance to Leishmania infection. Herein, leishmanial T-cell responses induced in subjects with low susceptibility to leishmaniasis as asymptomatic subjects were compared to those observed in cured cutaneous leishmaniasis (CCL) patients, who controlled the disease after antimonial therapy. All of them have shown maintenance of specific long-term immune responses characterized by expansion of higher proportions of CD4+ as compared to CD8+ Leishmania reactive T-lymphocytes. Asymptomatic subjects had lower indexes of in vitro Leishmania induced lymphoproliferative responses and interferon-gamma (IFN-gamma) production in comparison to CCL patients. On the other hand, interleukin (IL-10) production was much higher in asymptomatics than in CCL, while no differences in IL-5 levels were found. In conclusion, long lived T-cell responses achieved by asymptomatic individuals differed from those who had developed symptomatic leishmaniasis in terms of intensity of lymphocyte activation (proliferation or IFN-gamma) and regulatory mechanisms (IL-10). The absence of the disease in asymptomatics could be explained by their intrinsic ability to create a balance between immunoregulatory (IL-10) and effector cytokines (IFN-gamma), leading to parasite destruction without producing skin tissue damage. The establishment of profiles of cell-mediated immune responses associated with resistance against Leishmania infection is likely to make new inroads into understanding the long-lived immune protection against the disease.

We evaluated in a prospective study the immune response of naive subjects to a single dose of inactivated Hepatitis A vaccine. Ninety-seven percent of the vaccinees sero-converted 1 month after vaccination and 93% were still positive 2 years later. All of the vaccinees had a strong booster response 2 years after the single dose. Avaxim was more immunogenic than Vaqta for the primary dose (p = 0.01 for sero-positivity, p < 0.001 for antibody level) but no differences were found after boosting with Avaxim. Performance of intense physical activity during the first month after a single vaccine dose was associated with lower antibody levels (p = 0.004). This study indicates that a single dose of inactivated HAV vaccine elicits protective immune memory for at least 2 years.

We have recently shown that CD8+ T cells mediate clearance of rotavirus infection in mice. B-cell-deficient J(H)D knockout (-/-) mice depleted of CD8+ T cells become chronically infected with murine rotavirus, and beta2 microglobulin -/- and other mice depleted of CD8+ T cells have a 1- to 4-day delay in clearance of primary rotavirus infection. A role for CD8+ T cells in protection from reinfection with rotavirus was suggested by these studies, because J(H)D -/- mice rechallenged 6 to 8 weeks after primary infection shed smaller quantities of viral antigen and for fewer days than naive mice. Here we show that 8, 11, 13, and 18 days after primary infection the J(H)D -/- mice are almost completely resistant to reinfection and that they are still partially protected from reinfection 6 weeks, 5 months, and 8 months after primary infection. Protection against reinfection was dependent on CD8+ T cells, since J(H)D -/- mice depleted of CD8+ T cells by administration of an anti-CD8 monoclonal antibody became chronically infected with rotavirus upon rechallenge 13 days, 18 days, 6 weeks, and 5 months after primary infection. Thus, CD8+ T cells can actively mediate almost complete short-term and partial long-term protection from reinfection.

Infection of mice with sporozoites of Plasmodium berghei or Plasmodium yoelii has been used extensively to evaluate liver-stage protection by candidate preerythrocytic malaria vaccines. Unfortunately, repeated success of such vaccines in mice has not translated readily to effective malaria vaccines in humans. Thus, mice may be used better as models to dissect basic parameters required for immunity to Plasmodium -infection than as preclinical vaccine models. In turn, this basic information may aid in the rational design of malaria vaccines. Here, we describe a model of circumsporozoite-specific memory CD8 T cell generation that protects mice against multiple P. berghei sporozoite challenges for at least 19 months. Using this model we defined a threshold frequency of memory CD8 T cells in the blood that predicts long-term sterilizing immunity against liver-stage infection. Importantly, the number of Plasmodium -specific memory CD8 T cells required for immunity greatly exceeds the number required for resistance to other pathogens. In addition, this model allowed us to identify readily individual immunized mice that exceed or fall below the protective threshold before infection, information that should greatly facilitate studies to dissect basic mechanisms of protective CD8 T cell memory against liver-stage Plasmodium infection. Furthermore, the extremely large threshold in memory CD8 T cell frequencies required for long-term protection in mice may have important implications for development of effective malaria vaccines.

I read with interest the article by Metodi et al.1 In a cross-sectional study, the authors found that more than two-thirds of children under 5 years age who had received DPT-HB at 4, 8 and 12 weeks...

Background Feline leukaemia virus (FeLV) is a pathogen causing fatal illness in cats worldwide, and as such there is a high demand for products to protect against disease. The duration of immunity provided by an inactivated FeLV vaccine, Versifel FeLV, when administered to cats of the target age was determined. Kittens received two vaccinations when aged 7 to 9 weeks old, and were subsequently challenged up to 36 months later with the FeLV-A Glasgow isolate. Results In all studies, all of the younger aged control kittens showed persistent FeLV p27 antigenaemia confirming that the challenge virus was severe and efficacious. In contrast, the control cats did not show the required level of persistent antigenaemia, with a maximum of 45% cats affected in the middle duration study and only 10% in the longer study. However, apart from one animal in the short duration study, all of the cats vaccinated with Versifel FeLV were negative for persistent antigenaemia and can be considered treatment successes. Conclusion In conclusion, we have shown that although age-related resistance to infection with a virulent FeLV challenge is evident from as early as 10 months of age, vaccination with Versifel FeLV may aid in the protection of cats from FeLV related disease up to three years after primary vaccination as kittens.

1453 Factors Influencing Long-Term Immunity Against Hepatitis B - the Role of Natural Boosters

Summary Using a set of immunological methods, we established the signs of a primary immune response to influenza A(H1N1) in all 81 individuals tested who had fallen ill during the A(H1N1) epidemic outbreaks of 1977–1979, independent of their age: 23 of them were born before 1956, the remaining 58 after 1956. Thus, the persons who had already been in contact with A(H1N1) viruses circulating in the 1947–1956 period possessed sufficient protection against the A(H1N1) variant which reappeared in 1977, and this was the main reason why they did not fall ill during the second virus epidemic.

The duration of immunity produced by Rev. 1 vaccine was tested by exposing pregnant sheep to aborting donor animals infected with virulent Br. melitensis. One group consisted of 38 ewes vaccinated at 15 months of age and challenged 2 1 3 years later, a second of 16 ewes vaccinated at 22 months of age during lactation or pregnancy, and a third of 29 lambs vaccinated at 4 months of age and challenged 18 months later. Non-vaccinated ewes of a similar age were exposed at the same time. Infection was determined by the bacteriological examination of aborted materials, dead lambs, placentae, vaginal swab and milk samples taken at frequent intervals, and tissues at autopsy five weeks after parturition. All vaccinated sheep were equally well protected against heavy exposure which caused a high level of infection in non-vaccinated controls since only five of 83 vaccinated sheep were heavily infected at autopsy as compared with 19 of 29 non-vaccinated sheep. In a previous experiment performed under similar conditions, sheep which were vaccinated with Rev. 1 at 15 months of age and challenged 5 months later showed a similar degree of protection. It was therefore concluded that a single inoculation of Rev. 1 vaccine is able to stimulate effective immunity which persists for at least 2 1 3 years. Sixty-eight ewes vaccinated at 15 months of age were observed through two normal pregnancies following vaccination. No evidence of excretion of the vaccine strain was obtained in the bacteriological examination of placentae, vaginal swab and milk samples, nor in fourteen ewes vaccinated during lactation. Two ewes vaccinated while pregnant excreted the vaccine strain in vaginal swab and milk cultures for about 30 days after parturition, but not after the next parturition. It was concluded that excretion of Rev. 1 in the milk of vaccinated sheep in Iran would not be a problem.

Prevention of perinatal hepatitis B includes: (1) screening ol pregnant women for hepatitis B surface antigen, and (2) immunoprophylaxis of babies at risk. HBIG treatment seems to be of some efficacy in preventing the HBsAg carrier state while it permits passive active immunization to occur. The disadvantage of HBIG is that it confers only temporary immunity. Therefore, it infection does not occur, babies will still be susceptible to the virus when passively administered anti-HBs will no longerbe circulating. On the other hand, vaccine provides a long term but not immediate protection. Therefore the ideal approach in post-exposure prophylaxis is a combination of passive plus active immunization. The aim is to provide an immediate protection, with the HBIG, and a long term immunity, with the vaccine, to babies born to HBsAg carrier mothers.

Do students taking a one semester supplementary, remedial course acquire a long term immunity to failure?