Vaccine-related Reactions Research Articles

Phase I Trial of Viral Vector-Based Personalized Vaccination Elicits Robust Neoantigen-Specific Antitumor T-Cell Responses.

Personalized vaccines targeting multiple neoantigens (nAgs) are a promising strategy for eliciting a diversified antitumor T-cell response to overcome tumor heterogeneity. NOUS-PEV is a vector-based personalized vaccine, expressing 60 nAgs and consists of priming with a nonhuman Great Ape Adenoviral vector (GAd20) followed by boosts with Modified Vaccinia Ankara. Here, we report data of a phase Ib trial of NOUS-PEV in combination with pembrolizumab in treatment-naïve patients with metastatic melanoma (NCT04990479). The feasibility of this approach was demonstrated by producing, releasing, and administering to 6 patients 11 of 12 vaccines within 8 weeks from biopsy collection to GAd20 administration. The regimen was safe, with no treatment-related serious adverse events observed and mild vaccine-related reactions. Vaccine immunogenicity was demonstrated in all evaluable patients receiving the prime/boost regimen, with detection of robust neoantigen-specific immune responses to multiple neoantigens comprising both CD4 and CD8 T cells. Expansion and diversification of vaccine-induced T-cell receptor (TCR) clonotypes was observed in the posttreatment biopsies of patients with clinical response, providing evidence of tumor infiltration by vaccine-induced neoantigen-specific T cells. These findings indicate the ability of NOUS-PEV to amplify and broaden the repertoire of tumor-reactive T cells to empower a diverse, potent, and durable antitumor immune response. Finally, a gene signature indicative of the reduced presence of activated T cells together with very poor expression of the antigen-processing machinery genes has been identified in pretreatment biopsies as a potential biomarker of resistance to the treatment.

Retrospective analysis of healthcare workers admitted to emergency department due to side effects of the inactivated COVID-19 vaccine

Objective: This study aimed to evaluate the clinical characteristics and outcomes of healthcare workers who presented to the emergency department with vaccine-related reactions following the first dose of the CoronaVac vaccine. Materials and Methods: A retrospective analysis was conducted in Ankara Bilkent City Hospital’s Emergency Department between 13.01.2021 and 13.02.2021, encompassing healthcare workers aged 18 and above who experienced Vaccine Adverse Effects after CoronaVac vaccination. Data regarding demographics, medical history, symptoms, treatments, and outcomes were extracted from the hospital management system and analyzed using SPSS Version 24. Results: Of the 43 healthcare workers presenting with Vaccine Adverse Effects, 76% were female. Known history of anaphylaxis/urticaria was recorded in 32.6% of the patients, while 11.6% had a prior history of COVID-19. Common presenting symptoms included chest pain (16.3%) and headache (14%). A majority (58.1%) required no treatment, though two patients received adrenaline for anaphylaxis, with one requiring hospitalization. The median time from vaccination to symptom onset was approximately 16 hours. Conclusion: The study demonstrates a higher incidence of Vaccine Adverse Effects among female healthcare workers and those with a history of anaphylaxis/urticaria, although most reactions were mild and did not necessitate treatment. This analysis sheds light on the CoronaVac vaccine’s safety profile among healthcare workers and provides a foundation for addressing vaccine-related concerns in preparation for future mass vaccination endeavors against emerging COVID-19 variants or new pandemics.

The Effects of Vaccines on the Sequelae Rates of Recurrent Infections and the Severity of Pulmonary COVID-19 Infection by Imaging.

Although vaccines have been shown to reduce the number of COVID-19 infection cases significantly, vaccine-related reactions, long COVID-19 syndrome, and COVID-19 infection following vaccination continue to be a burden on healthcare services and warrant further scientific research. The purpose of this study was to research the severity of pulmonary COVID-19 infection following vaccination and the sequelae rates of recurrent infections in vaccinated cases by imaging. Patients who underwent follow-up CTs at 1 month, 3 months, and 6 months in our hospital with a diagnosis of COVID-19 were scanned retrospectively. Furthermore, all essential information was gathered from patients' immunization records. The major findings of our study were: (1) sequelae were frequently observed in unvaccinated cases; (2) the correlation between vaccination status and the severity of sequelae was significant; (3) there was not any significant relationship between the vaccine type and the severity of sequelae; and (4) hematocrit, hemoglobin, and lymphocyte parameters may be used as predictors of sequelae rates. COVID-19 infection, although reduced in prevalence following the development of vaccines, still remains a public health concern because of reinfection. Vaccination not only appears to protect against primary infection, but also seems to reduce reinfection and sequalae rates following reinfection.

COVID-19 Vaccine Acceptance During Pregnancy, Women's Views, and Influencing Factors.

COVID-19 vaccination is advised for pregnant women all over the world; however, vaccine acceptance is variable across the globe. This study was conducted by enrolling 292 antenatal women attending the outpatient department (OPD) in a tertiary care hospitalin Delhi, India, between August 1, 2022 and October 31, 2022, with the aim to determine the acceptability of vaccination against COVID-19 disease in pregnancy, women's views regarding the vaccine and to ascertain reasons for acceptance or denial during pregnancy. Of the 292 pregnant women who completed the questionnaire, 39.73% had received both doses of vaccination against COVID-19 disease before pregnancy, and 39.04% had received a singledose. Twenty-one percent of women did not receive any vaccine. Eighty-four percent of the unvaccinated and 35% of the women with a single dose of thevaccine refused further doses during pregnancy. The most common concern was the fear that the vaccine might cause harm to the fetus (35.3%), followed by the fear of vaccine-related reactions (25.4%). Also, 14.6% of women feared that the vaccine might cause them to abort the ongoing pregnancy. Thirteen percent of women stated their intent to receive the vaccine after they were informed regarding its safety and requirement. No difference was found in the acceptability of the vaccine based on the educational status of women or on the monthly income of the families. Adequate communication regarding safety information on COVID-19 vaccines is a must forpregnant women and their families to provide reassurance about the need and safety of the vaccines. It would facilitate making informed decisions and is likely to be helpful in increasing vaccine acceptance.

Real-world safety profile of the 9-valent human papillomavirus vaccine: A study in Zhejiang, China from 2019 to 2021

ABSTRACT The safety profile of the 9-valent human papillomavirus vaccine (9vHPV) was evaluated based on the reporting rate of adverse events following immunization (AEFI) obtained from the passive surveillance data in Zhejiang. The 9vHPV AEFI reports in Zhejiang were collected and reviewed from the National Adverse Event Following Immunization Surveillance System (NAEFISS) from 2019 to 2021. Reporting rates of AEFI were analyzed under multiple aspects, including age, city, number of vaccinations, AEFI categories, and diagnosis categories. This study used the reporting odds ratio (ROR) for anomalous signal assessment. The NAEFISS collected 331 AEFI reports after administering 1,064,851 doses of 9vHPV, with a crude AEFI rate of 3.12/10,000 doses. The third dose had the highest reporting rate of minor vaccine-related reaction (n = 80, 3.06 per 10,000), followed by the first dose (n = 134, 2.98 per 10,000), and second dose (n = 76, 2.15 per 10,000). Fever/redness/induration was the most common minor adverse event (281 records, 2.64/10,000 doses). Nine cases of urticaria, ten cases of allergic rash, and ten cases of syncope were recorded. This study found a positive signal association between 9vHPV immunization and adverse events such as syncope, encephalitis, sterile abscess, and urticaria. This study did not identify any new emerging safety concerns. In the future, more research is needed to validate and further explore adverse reactions associated with 9vHPV.

A real-world prospective cohort study of immunogenicity and reactogenicity of ChAdOx1-S[recombinant] among patients with immune-mediated dermatological diseases

Immunogenicity and reactogenicity of COVID-19 vaccines have been established in various groups of immunosuppressed patients; however, studies involving patients with immune-mediated dermatological diseases (IMDDs) are scarce. To investigate the influence of IMDDs on the development of SARS-CoV-2-specific immunity and side-effects following ChAdOx1-S[recombinant] vaccination. This prospective cohort study included 127 patients with IMDDs and 97 participants without immune-mediated diseases who received ChAdOx1-S[recombinant]. SARS-CoV-2-specific immunity and side-effect profiles were assessed at 1 month postvaccination and compared between groups. Immunological (primary) outcomes were the percentages of participants who tested positive for neutralizing antibodies [seroconversion rate (SR)] and those who developed T-cell-mediated immunity demonstrated by an interferon-γ-releasing assay (IGRA) [positive IGRA rate (+IGRA)]. Reactogenicity-related (secondary) outcomes were the unsolicited adverse reactions and worsening of IMDD activity reflected by the uptitration of immunosuppressants during and within 1 month of vaccination. Overall, the SR for the IMDD group was similar to that of participants without immune-mediated conditions (75·6 vs. 84·5, P = 0·101), whereas + IGRA was lower (72·4 vs. 88·7, P = 0·003). Reactogenicity was similar between groups. No severe adverse reaction was reported. By stratifying the participants in the IMDD group according to individual disease, the immunogenicity of the vaccine was lowest in patients with autoimmune bullous diseases (AIBD) (SR 64·5%, +IGRA 62·9%) and highest in patients with psoriasis (SR 87·7%, +IGRA 80·7%). The reverse trend was found for vaccine-related reactions. Immunosuppressants were uptitrated in 15·8% of cases; 75% of these were patients with AIBD. Among participants with IMDDs, ChAdOx1-S[recombinant] showed good immunogenicity among patients with psoriasis, but demonstrated lower levels of immunogenicity for patients with AIBD. Some patients, especially patients with AIBD, should be closely monitored as they may require treatment escalation within 1 month postvaccination.

New-onset lichen planus and lichen planus flare in elderly women after COVID-19 vaccination.

Dear Editor, Owing to the widespread use of COVID-19 vaccines, the number of cutaneous vaccine-related adverse events has recently increased.1 We present two cases of lichen planus in elderly women following COVID-19 mRNA vaccination. The first patient presented with new-onset LP, whereas the second patient experienced an extensive LP flare after a 10-year remission. The first patient was an 82-year-old woman who developed an extensive pruritic rash 14 days after receiving a second dose of the Pfizer-BioNTech COVID-19 vaccine. Other possible triggers such as recent infections, medication changes, or stressful events preceding the eruption were ruled out. The patient had no significant medical history, other than well-controlled arterial hypertension. On physical examination, she had polygonal, purpuric, scaly papules in the axillary region, flexural wrists and forearms, ankles, buttocks, lower back, and abdomen (Figure 1). Mucosal lesions were not observed. Dermoscopy revealed mild desquamation and Wickham's striae. Skin biopsy demonstrated irregular epidermal hyperplasia with hypergranulosis and hyperkeratosis, vacuolar degeneration of the basal layer, and dense lymphocytic infiltrate in the superficial dermis (Figure 1). Considering the clinical presentation, histopathological analysis, and absence of an alternative trigger, we diagnosed LP triggered by the mRNA COVID-19 vaccine. Thus, we began treatment with prednisolone 20 mg daily, tapering the dose over 6 weeks, which resulted in gradual improvement of skin lesions. The second patient was a 68-year-old woman with a 2-week history of an intensely pruritic eruption that occurred 14 days after receiving a second dose of the Moderna COVID-19 (mRNA-1273) vaccine. Her medical history included arterial hypertension, hyperlipidemia, obesity, HLA-B27 spondyloarthritis, and LP, which was histologically confirmed 10 years ago and successfully treated with systemic and topical corticosteroids. During the examination, erythematous to violaceous squamous papules were discovered on the trunk, buttocks, and extremities, as well as around the ankles, flexural wrists, forearms, and axillary folds, with palmar involvement as well (Figure 2). Mucosal or nail lesions were absent. Dermoscopy revealed slight scaling and Wickham's striae, and a skin biopsy confirmed lichen planus. Therefore, we introduced 30 mg prednisolone, and tapered the dose to discontinuation over 6 weeks, which lead to the resolution of skin lesions. LP is a chronic inflammatory T-cell-mediated skin disease caused by various infections, drugs, and, in rare cases, vaccines.1-6 The most common vaccines causing LP are hepatitis B and influenza vaccines. Recently, the new-onset or reactivation of LP has been associated with COVID-19 infection and vaccination. Although most reported cases of LP following COVID vaccination were localized, we observed two cases of widespread LP.2-5 The majority of vaccine-related reactions occur in middle-aged women, implying an increased risk of such reactions in women, even in elderly ones, as observed in our cases.1, 6 Both our patients developed LP 14 days after receiving the second dose of mRNA COVID-19 vaccine, which is consistent with vaccine-related LP time onset.6 The immunopathogenesis of vaccine-induced LP likely involves Th1 cell activation with upregulation of proinflammatory cytokines IL-2, TNF-alpha, and IFN-y, which leads to apoptosis of basal keratinocytes, a hallmark of LP. However, the precise mechanism underlying LP (re)activation following vaccination remains unknown. Similarly, immune dysregulation after COVID-19 vaccination may result in the (re)activation of other immune-mediated skin diseases such as psoriasis, vitiligo, acne vulgaris, pemphigus vulgaris, and certain connective tissue diseases.2, 5 Likewise, COVID-19 pandemic has underlined the importance of dermatologists and rheumatologists in providing guidance regarding immunosuppressive and biological therapy considering their extensive experience with such treatments, as well as recognizing the immune-mediated aspects of COVID-19 infection and vaccination.7 Furthermore, as a result of a better understanding of COVID-19 disease mechanisms, novel therapeutic strategies utilizing adipose-derived mesenchymal stem cells (AD-MSCs) are being developed, and given their immuno-modulatory properties, could be employed to combat the disease.8 Finally, dermatologists should be aware of new-onset or flare-ups of LP in older women caused by COVID-19 vaccination as well as the possible (re)activation of other immune-mediated skin diseases. N.H. wrote the original manuscript. T.Z., S.P., and I.B. performed literature research and contributed to the analysis of the data. M.K. and L.P.M. performed supervision, and writing—review and editing. The authors declare no conflicts of interest. Authors declare human ethics approval was not needed for this study. The data that support the findings of this study are available from the corresponding author upon reasonable request. Written informed consent was obtained from the patients for the publication of this case report and accompanying images.

Allergy evaluation of messenger RNA vaccine reactions is crucial, with a specific role for polyethylene glycol testing

Allergy evaluation of messenger RNA vaccine reactions is crucial, with a specific role for polyethylene glycol testing

Abstract #1185161: Thyroiditis Related to mRNA-Based SARS-CoV-2 Vaccination: A Case Series

The proliferation of SARS-CoV-2 vaccines in late 2020 was a significant moment in the journey to end a worldwide pandemic. In the United States it also marked the first widespread and urgent vaccination campaign amongst all areas of the adult population in nearly a century. Vaccine related reactions are of keen interest given the necessity of vaccination to stem transmission and severity of disease. ASIA (Schoenfeld) Syndrome is a condition related to adjuvants within vaccine formulations that precipitate adverse events including thyroiditis.

Çocukluk Yaş Grubunda Karaciğer Nakli Öncesi ve Sonrası Zayıflatılmış Canlı Aşı Uygulamaları-Türkiye’den Tek Merkez Deneyimi

The aim of this study was to evaluate the attenuated live vaccine administration before and after liver transplantation. This study was carried out at the Child Health Surveillance Unit of the Social Pediatrics Department. Besides healthy children, children with special needs are being followed-up at the Unit. Each child has a personal health record in the unit. The health records of patients who had received attenuated live vaccine before liver transplantation under 1 year of age or after liver transplantation were evaluated. Demographic characteristics, data showing immunologic status before vaccination, vaccine related reactions and serologic responses were obtained from health records of each child. Retrospective files of 5 patients who were in follow-up were examined. Four patients at least 2 years after the liver transplantation had attenuated live vaccination (measles-mumps-rubella vaccine and / or chickenpox vaccine). No adverse reaction was noted after the immunization among these 4 children. A 6-month-15-day-old infant who was a candidate for liver transplantation had been vaccinated with measles-mumps-rubella and chickenpox vaccine and it was determined that the serological response after vaccination was not complete in the baby who did not have any adverse reactions after vaccination. Our findings demonstrated that despite the use of immusuppressive therapy, it is safe to apply attenuated live vaccines after the transplantation if appropriate conditions were provided. The timing of the rapid effective immunization before transplantation under one year of age needs to be further investigated

The art of prevention: COVID-19 vaccine preparedness for the dermatologist.

As COVID-19 vaccinations begin, dermatologists must be aware of the cutaneous adverse events reported in the clinical trials, including injection site and hypersensitivity reactions, and emerging evidence of dermal filler injection reactions after vaccination. The filler reaction may represent the development of a delayed-type hypersensitivity in the setting of another immunologic trigger (i.e., the vaccine). After conducting a literature review of similar reactions, their pathophysiology, and management, we present a set of timely clinical considerations for counseling, prevention, and management of possible cutaneous sequelae of the COVID-19 vaccine. We encourage documentation of vaccine-related reactions to aid the safety data collection in the Vaccine Adverse Event Reporting System and the American Academy of Dermatology COVID-19 Registry.

Analysis on the characteristics of suspected vaccine-related deaths in Fujian Province, 2012-2017

Objective: To analyze the characterisitics of the death cases suspected to be related to vaccination in Fujian Province from 2012 to 2017. Methods: A total of 33 death cases information which was suspected to be related to the vaccinations from 2012 to 2017 were extracted from Chinese Adverse Events Following Immunization Information System (AEFI). The autopsy reports and the conclusions made by AEFI investigation diagnosis expert committee were collected at the same time. The inoculation data were obtained through the Fujian province Immunization Program Information System. The AEFI incidence, rare vaccine reaction incidences and mortality rates following immunization were figured out to analyze the characterisitics of the death cases associated with vaccination. Results: The age of deuths cases was from 26 days to 52 months. Among 33 cases, 23 were males, and 8 were due to vaccine-related reaction, and the others were due to coincidental events. The number of rare vaccine reaction cases from 2012 to 2017 were 2,3,6,8,7 and 7, respectively. The highest AEFI incidence was measles and rubella combined attenuated live vaccine [38.88 (95%CI: 36.85-40.91)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [2.01 (95%CI: 1.73-2.30)/100 000 dose]. The highest rare vaccine reaction incidence was measles and rubella combined attenuated live vaccine [15.04 (95%CI: 13.78-16.30)/100 000 dose], and the lowest was trivalent oral poliomyelitis attenuated live vaccine [0.38 (95%CI: 0.25-0.50)/100 000]. The highest mortality rate was inactivated poliomyelitis vaccine [0.26 (95%CI: 0.04-0.54)/100 000 doses], and the lowest mortality rate was measles, mumps and rubella combined attenuated live vaccine [0.01 (95%CI: 0.00-0.08)/100 000 doses]. The Spearman correlation analysis showed that there were correlations between AEFI incidence and rare vaccine reaction incidence (r=0.64, P=0.048), there were no correlations between AEFI incidence and mortality rate (r=-0.34, P=0.329), and there were no correlations between rare vaccine reaction incidence and mortality rate (r=-0.25, P=0.484). Conclusion: Neither AEFI incidence nor rare vaccine reaction incidence was correlation with mortality rate. The main causes of death following vaccination were coincidental events.

GELATIN-INDUCED VACCINE ANAPHYLAXIS MISATTRIBUTED TO EGG ALLERGY

Introduction Vaccine-related anaphylaxis is rare, occurring at a rate of 1 per million vaccine doses. All suspected anaphylactic reactions should be evaluated with allergy testing to both the vaccine and its components. We report on a case of anaphylaxis following both 12- and 15-month immunizations. Case Description A 17-month old male was referred for evaluation of anaphylaxis to vaccines. At 12 months of age he received initial doses of Influenza, MMR, Hepatitis A, and Pneumococcal 13-valent vaccines. Fifteen minutes following administration he developed coughing, pruritus, and facial/lip angioedema. He was evaluated in an ED and received intramuscular epinephrine for presumed influenza vaccine anaphylaxis secondary to egg hypersensitivity. Three months later he developed cough and facial/lip angioedema within five minutes of his 15-month immunizations (Varicella, DTaP, and Haemophilus B vaccines). Skin testing was positive for Gelatin (11 mm), Egg (9 mm), MMR (5 mm), and Varicella (9 mm), and negative to Influenza (3 mm) with appropriate histamine and saline controls. RAST testing was positive to Bovine Gelatin (25.1 kU/L) and negative to Egg ( Discussion A previous study of MMR vaccine anaphylaxis found 27% of affected patients had anti-gelatin IgE, while none reported gelatin food allergy. MMR, Varicella, Zoster, and Rabies vaccines contain >10,000μg of gelatin/dose with much smaller amounts in influenza vaccines. We concluded that our patient was sensitized to gelatin, and reacted to gelatin-containing vaccines. Proper allergy evaluation is essential following vaccine-related reactions, as unnecessary avoidance can be associated with serious health consequences.

Maternal Immunization in Argentina: Nationwide Strategy

Background: Immunization against flu and pertussis is prioritized within the comprehensive care strategy for pregnant women (PW) and small infants in Argentina. Flu vaccine was included in the National Immunization Schedule (NIS) in 2011. Argentina recommended a vaccination strategy for PW against pertussis in 2012, with the aim of reducing complications and deaths related to both diseases. Objective: To describe the national strategy of maternal immunization, January 2011- October 2017. Methods & Materials: Descriptive study. National vaccination coverages (NVC) between 2011-2017, lethality rates and vaccines safety profile were analyzed. Adverse events following immunization (AEFI) notifications were performed passively. Rates (R) are expressed in 100,000 doses. Results: Between 2011-2017, 2,540,601 doses of flu vaccine were applied (NVC >95% most years). There were no notifications of influenza related deaths in vaccinated PW during this period. There were 16 notified AEFI (R 0.6): 6 vaccine related reactions (5 mild, 1 severe*); 5 program errors; a case of flaccid paralysis classified as non-conclusive event due to lack of complementary studies. In 2012, Tdap was recommended after the 20th gestation week. Between 2012-2017, 2,557,432 doses were applied. NVC 2012-2016 were 50.9%, 67.1%, 70.9%, 61.7%, 65.3%, respectively. 47 AEFI were reported (R:1.8), 12 vaccine related (1 severe*) and 1 anxiety disorder. Program errors were 31 (66%; R:1.2). Comparing previous and post vaccination strategy, the global pertussis lethality rate dropped 68.8% (p < 0.001) globally and 84.1% (p < 0.001) in infants less than 2 months. *The notified severe reaction vaccine was a case of Guillain-Barre syndrome after flu and Tdap vaccination, without sequelae. It was not possible to attribute the AEFI to one particular vaccine. Conclusion: Argentina became the first Latin-American country to set a strategy of vaccination against pertussis universally. Since 2012 a downward trend in pertussis mortality was evident and no deaths from influenza in vaccinated were notified in PW. The adequate safety profile of both vaccines in PW is reassuring.

Parents' and providers' attitudes toward school-located provision and school-entry requirements for HPV vaccines

ABSTRACTObjective: To determine parents' and providers' attitudes toward school-located provision and school-entry requirements for HPV vaccination. Methods: Parents/guardians of 11–17 y old girls and pediatric healthcare providers at one inner-city public clinic and three private practices completed semi-structured interviews in 2012-2013. Participants were asked open-ended questions regarding their attitudes toward school-located provision and school-entry requirements for HPV vaccination. Parents' answers were analyzed with relationship to whether their daughters had not initiated, initiated but not completed, or completed the HPV vaccine series. Qualitative analysis was used to identify themes related to shared views. Results: 129 parents/guardians and 34 providers participated. 61% of parents supported providing HPV vaccinations in schools, citing reasons of convenience, improved access, and positive peer pressure. Those who opposed school-located provision raised concerns related to privacy and the capacity of school nurses to manage vaccine-related reactions. Parents whose daughters had not completed the series were more likely to intend to vaccinate their daughters in schools (70%) and support requirements (64%) than parents who had not initiated vaccination (42% would vaccinate at school, 46% support requirements) or completed the series (42% would vaccinate at school, 32% support requirements; p < 0 .05 for all comparisons). 81% of providers supported offering vaccination in schools, wanting to take advantage of the captive audience, improve vaccine completion rates, and decrease the administrative burden on medical office staff, but were concerned about adequate information transfer between schools and medical offices. Only 32% of providers supported school-entry requirements, largely because they felt that a requirement might provoke a public backlash that could further hinder vaccination efforts. Conclusions: School-located provision of HPV vaccination was widely accepted by healthcare providers and parents whose children have not completed the series, indicating that this venue might be a valuable addition to improve completion rates. Support for school-entry requirements was limited among both parents and healthcare providers.

Considerations on immunization anxiety-related reactions in clusters

A cluster of adverse events following immunization (AEFI) represents a stress test for an immunization program. The community can suspect on vaccine-related reaction leading to mistrust on the immunization program. An immunization anxiety-related reaction is one of the hypotheses to be tested and can be reasonably accepted when the vaccine-related and immunization error-related reactions are ruled out and no coincidental events can explain the cases. Immunization program approaches widely accepted to understand and respond to adverse events are root-cause analysis and systems analysis. Psychiatric cognitive frame will support the root-cause analysis assigning a causal relationship to individual temporary disorders of the affected vaccinees. Communication will focus on vaccine safety and absence of errors in the immunization program. Systems analysis addresses the whole context considering the fear spread as a systemic threat. Socio-psychological frame offers a broader opportunity to understand and respond to a specific community. Management is based on communication to change community belief in misperceptions of vaccine risks and support the idea of immunization as a causal factor, different from the vaccine. Communities can consider use of psychiatric labels, Mass Psychogenic Illness or Mass Hysteria, as an act of inconsiderateness. Labels like immunization anxiety-related reactions in clusters or collective immunization anxiety-related reactions are recommended to bridge the causal perception of the community with the result of the scientific investigation of the cases.

Application of the immunological disease continuum to study autoimmune and other inflammatory events after vaccination

In vaccine safety monitoring, the evaluation of possible autoimmune events is challenging. Developing grouping systems based on pathophysiology, instead of organ systems, may enhance our ability to identify or verify associations between vaccines and adverse immunologically mediated events in clinical trials and post-licensure surveillance. Emerging data suggest that self-directed tissue inflammation occurs along a continuum from innate immune-driven diseases to adaptive immune-driven diseases. Herein, we develop this proposed classification for the vaccination setting in which inflammatory diseases are placed along a continuum according to the two major arms of the immune system, the innate immune arm (mediated by cells including neutrophils, macrophages and complement) and the adaptive immune arm (cell-mediated and humoral response). We incorporate hypersensitivity reactions and molecular mimicry vaccine-related reactions into this mechanistic scheme. We show how this could have important implications to assess mechanisms of potential immune-mediated adverse events following vaccination.

Adversomics: the emerging field of vaccine adverse event immunogenetics.

Poland, Gregory A. MD*; Ovsyannikova, Inna G. PhD†; Jacobson, Robert M. MD‡ Author Information

Few young children had mild reactions to the measles, mumps, and rubella vaccine and older children had nearly no vaccine related reactions

Few young children had mild reactions to the measles, mumps, and rubella vaccine and older children had nearly no vaccine related reactions

Dose response of A/Alaska/6/77 (H3N2) cold-adapted reassortant vaccine virus in adult volunteers: role of local antibody in resistance to infection with vaccine virus.

An attenuated influenza A candidate vaccine virus, derived from the A/Ann Arbor/6/60 (H2N2) cold-adapted (ca) donor virus and the A/Alaska/6/77 (H3N2) wild-type virus, was evaluated in adult seronegative volunteers (serum hemagglutination-inhibiting antibody titer, less than or equal to 1:8) for level of attenuation, infectivity, antigenicity, and genetic stability. Four groups with similar preinoculation mean titers of serum and nasal wash antibodies were inoculated intranasally with 10(4.5), 10(5.5), 10(6.5), or 10(7.5) 50% tissue culture infectious doses (TCID50) of the ca reassortant virus, and eight other seronegative adult volunteers received the wild-type virus. Only 2 of 66 vaccinees developed fever or mild and brief systemic or upper respiratory tract illness or both. Both volunteers with vaccine-related reactions received the highest dose (10(7.5) TCID50) of ca virus, which indicates that the vaccine retains some mild reactogenicity at a high dosage. In contrast, four of eight volunteers infected with the wild-type virus became ill. Each of the 54 isolates tested retained the temperature-sensitive phenotype of the vaccine virus. Thus, the ca reassortant was genetically stable and attenuated at 10(4.5) to 10(7.5) TCID50 for seronegative adults. The 50% human infective dose of ca virus was approximately 10(5.3) TCID50. Ten and one hundred 50% human infectious doses infected 73 and 83% of vaccinees, respectively, and approximately 75% developed an immunological response at these doses. The failure of the vaccine virus to infect some volunteers was correlated with the presence of pre-inoculation nasal wash immunoglobulin A hemagglutinin antibody.