Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection

Although antibody levels progressively decrease following SARS-CoV-2 infection, the immune memory persists for months. Thus, individuals who naturally contracted SARS-CoV-2 are expected to develop a more rapid and sustained response to COVID-19 vaccines than naïve individuals. In this study, we analyzed the dynamics of the antibody response to the BNT162b2 mRNA COVID-19 vaccine in six healthcare workers who contracted SARS-CoV-2 in March 2020, in comparison to nine control subjects without a previous infection. The vaccine was well tolerated by both groups, with no significant difference in the frequency of vaccine-associated side effects, with the exception of local pain, which was more common in previously infected subjects. Overall, the titers of neutralizing antibodies were markedly higher in response to the vaccine than after natural infection. In all subjects with pre-existing immunity, a rapid increase in anti-spike receptor-binding domain (RBD) IgG antibodies and neutralizing antibody titers was observed one week after the first dose, which seemed to act as a booster. Notably, in previously infected individuals, neutralizing antibody titers 7 days after the first vaccine dose were not significantly different from those observed in naïve subjects 7 days after the second vaccine dose. These results suggest that, in previously infected people, a single dose of the vaccine might be sufficient to induce an effective response.     

Shedding of Ann Arbor strain live attenuated influenza vaccine virus in children 6-59 months of age

Background

A trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved for use in children 24 months of age and older in a number of countries. The incidence, duration, and other parameters of viral shedding after vaccination with LAIV have not been fully described in children ≤5 years of age.

Methods

An open-label, single-arm, multicenter, phase 2 study assessed viral shedding and safety in 200 children 6-59 months of age after a single, intranasal dose of LAIV in 2006. Participants were enrolled into 2 age groups: 6-23 months (n = 100) and 24-59 months (n = 100) of age. Viral shedding, reactogenicity, and adverse events were assessed for 28 days postvaccination. Serious adverse events and significant new medical conditions were monitored for 180 days postvaccination.

Results

Viral shedding was detected by culture in 79% (95% CI, 73-84) of vaccine recipients and occurred more frequently in children 6-23 months of age (89%) compared with children 24-59 months of age (69%). In total, 157 subjects shed vaccine, which was confirmed by RT-PCR as A/H1N1 for 128 subjects, A/H3N2 for 72 subjects, and B for 74 subjects. The incidence of shedding was highest on day 2 (59% in the 6-23 month age group; 41% in the 24-59 month age group) and most shedding occurred 1-11 days postvaccination; shedding after 11 days was infrequent and occurred almost exclusively in children 6-23 months of age. Mean titers of shed vaccine virus peaked on day 2 and were generally <10^3.0 median tissue culture infective dose/mL for both groups. Reactogenicity events peaked on day 2; runny/stuffy nose was reported most frequently (63% of all subjects).

Conclusion

Most children 6-59 months of age vaccinated with Ann Arbor strain LAIV shed ≥1 vaccine virus within 11 days of vaccination. Shedding was less common in children 24-59 months of age, a population for whom LAIV is approved for use. Titers of shed vaccine were low, which may explain why secondary transmission of LAIV was observed very infrequently in a previous controlled study conducted with young children in a daycare setting.     

Active immunization against hepatitis A in dialysis patients.

BACKGROUND: This study investigated the feasibility, immunogenicity, and reactogenicity of hepatitis A vaccination in end-stage renal failure patients who were on chronic intermittent haemodialysis. METHODS: Forty-three subjects were vaccinated with an inactivated hepatitis A vaccine according to a 0-, 1-, and 6-month immunization schedule. Two groups were established who received the vaccine either intramuscularly (group A, n=30) or subcutaneously (group B, n=13). RESULTS: All patients in group A and 12/13 in group B developed antibodies against hepatitis A. The geometric mean titres (GMT) were high and similar to those observed in healthy subjects. There was a tendency to higher GMT in the group who received the vaccine subcutaneously. No clinically significant adverse events were observed, and the liver enzyme profile showed no abnormalities. CONCLUSIONS: We showed that hepatitis A vaccination of dialysis patients is feasible, well tolerated and immunogenic and that the vaccine can be given subcutaneously in those patients where intramuscular administration is contra-indicated.     

Reactogenicity and immunogenicity of tetanus toxoid,reduced diphtheria toxoid,and acellular pertussis vaccine (Tdap) in pregnant and nonpregnant women

ObjectiveTetanus toxoid, reduced diphtheria toxoid, and acellular pertusiss (Tdap) vaccine is recommended during each pregnancy, regardless of prior receipt. Data on reactogenicity and immunogenicity, particularly after repeated Tdap, are limited. We compared local injection-site and systemic reactions and serologic response following Tdap in (1) pregnant and nonpregnant women and (2) pregnant women by self-reported prior Tdap receipt.Study designPregnant women (gestational age 20–34 weeks) and nonpregnant women receiving Tdap were enrolled in this observational study. Injection-site and systemic reactions were assessed for one week post-vaccination. Pertussis toxin, filamentous hemagglutinin, pertactin, fimbriae, tetanus and diphtheria specific IgG antibody titers were determined by standardized enzyme-linked immunosorbent assay at baseline and 28 days post-vaccination. Reactogenicity and serologic responses were compared by pregnancy status, and within pregnant women by self-reported prior Tdap receipt.Results374 pregnant and 225 nonpregnant women were vaccinated. Severe local or systemic reactions or “any” fever were uncommon (≤3% for both groups). Moderate/severe injection-site pain was significantly higher in pregnant (17.9%) versus nonpregnant (11.1%) women, but did not prompt a healthcare visit. Proportions of other moderate/severe or any severe reactions were not significantly higher in pregnant compared to nonpregnant women. Moderate/severe (including pain) and severe reactions were not significantly higher in pregnant women receiving repeat versus first-time Tdap. Antibody titers increased from baseline to post-vaccination for all vaccine antigens in pregnant and nonpregnant women; post-vaccination titers against pertussis toxin and filamentous hemagglutinin were significantly higher in nonpregnant versus pregnant women (p < 0.01).ConclusionTdap was well-tolerated in pregnant and nonpregnant women. Pregnant women were more likely to report moderate/severe pain at the Tdap injection-site compared with nonpregnant women, but did not necessitate medical visits. Prior Tdap receipt did not increase occurrence of moderate/severe local or systemic reactions in pregnant women. Serologic responses to all vaccine antigens were robust.Clinical Trial Registration@ClinicalTrials.gov. NCT02209623.https://clinicaltrials.gov/ct2/show/NCT02209623.     

Adverse events following immunization: real causality and myths

ABSTRACT

Introduction: To assure the highest safety of immunization programs, detect adverse events following immunization (AEFIs), eliminate concerns, and reduce the risk of low vaccination coverage, authorities in industrialized countries have collected years of reports of suspected AEFIs and have systematically assessed their clinical importance.

Areas covered: In this paper, the methods used to assess vaccine safety and the results obtained by the analysis of reports, studies, and meta-analyses are discussed.

Expert opinion: Severe AEFIs are rare, and all evaluations of safety of vaccines recommended for both children and adults have demonstrated that the advantages of vaccines are always significantly higher than the problems that they cause, and there is no need to modify recommendations. However, the definition of AEFI is dependent on the vaccines themselves, complicating the definition of an AEFI and explaining why doubts and concerns have been raised. Presently, disease epidemiology data collected in healthy people and in subjects with underlying disease, general vaccine coverage, and the vaccination status of subjects with AEFIs are managed by many independent institutions. Only strict co-operation between these institutions will lead to the successful identification of AEFIs and to a reduction of the weight of anti-vaccine arguments.     

猪鼻支原体vlp重复区融合蛋白的构建表达及反应原性分析

目的 猪鼻支原体(Mhr)是临床猪场常见病原菌之一,同时研究证实其与多种人类肿瘤有关。目前对Mhr的血清学检测尚无有效的方法。本研究以Mhr可变脂蛋白(vlp)家族为对象,设计vlp家族蛋白重复区片段融合蛋白,以作为检测用包被抗原使用。方法 根据大肠杆菌的密码子偏嗜性,设计并构建串联表达7种Mhr可变脂蛋白vlpA、B、C、D、E、F、G重复区片段的重组蛋白vlpA-G基因。将该基因片段装入pET-32a(+)载体中转化大肠杆菌,筛选鉴定获得阳性工程菌。IPTG诱导表达,镍柱亲和层析获得纯化的重组蛋白vlpA-G。Western Blot鉴定该重组蛋白与Mhr阳性血清的反应能力,并利用该重组蛋白为包被抗原初步建立间接ELISA方法用于检测猪血清中的Mhr抗体。结果 构建表达vlpA-G重组蛋白的基因工程菌,经PCR及DNA测序正确。IPTG诱导后出现明显蛋白条带,经镍柱亲和层析纯化获得vlpA-G重组蛋白。Western Blot试验证明重组蛋白vlpA-G能够和Mhr阳性兔血清产生明显的阳性杂交带;利用重组vlpA-G为包被抗原初步建立间接ELISA检测方法可成功检测Mhr阳性猪血清,证明该重组vlpA-G蛋白具有良好的反应原性。结论 本研究构建了重组蛋白vlpA-G并证实该蛋白具有良好的反应原性,可作为Mhr血清学诊断方法研究的候选抗原,同时也为Mhr重组蛋白疫苗提供可选抗原。     

Analysis of virus and host factors in a study of A/Peking/2/79 (H3N2) cold-adapted vaccine recombinant in which vaccine-associated illness occurred in normal volunteers

Live attenuated cold-adapted influenza vaccine is undergoing evaluation in man. Several strains have proven to be safe, immunogenic, nontransmissible, and protective against experimental challenge. In this study of A/Peking/2/79(H3N2), with six internal genes from the cold-adapted (Ca) parent A/Ann Arbor/6/60(H2N2), we encountered at the highest input multiplicity, 28% illness rate among individuals infected with vaccine. Reversion to wild type and excessive viral replication did not occur. Physical characteristics of the vaccine were similar to nonreactogenic vaccine A/Washington/897/80(H3N2). At ten- and 100-fold lower input multiplicities, infection frequency was maintained, but reactions did not occur. We compared the observations in this study with those made in a similar study of A/Scotland/840/74(H3N2), a cold-adapted vaccine with five genes from the Ca parent in which reactogenicity also was noted. The dose of vaccine virus in relation to tissue culture infectious doses required to infect 50% of susceptibles (HID50) was proportionally lower for both A/Peking/2/79(H3N2) and A/Scotland/80(H3N2). Hence, when the vaccine was undiluted the recipients were inoculated with more than 100 HID50. We concluded that the very high input could be avoided if vaccines were screened beginning at 1/1,000 of maximum titers. Ca vaccines must be safe before they undergo field trials.     

An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2-17 years

Please cite this paper as: Ambrose et al. (2011) An integrated, multistudy analysis of the safety of Ann Arbor strain live attenuated influenza vaccine in children aged 2–17 years. Influenza and Other Respiratory Viruses 5(6), 389–397. Background Trivalent, Ann Arbor strain, live attenuated influenza vaccine (LAIV) is approved in several countries for use in eligible children aged ≥2 years. Objective To describe the safety of Ann Arbor strain LAIV in children aged 2–17 years. Methods An integrated analysis of randomized, controlled trials of LAIV. Results A total of 4245 and 10 693 children received ≥1 dose of LAIV in year 1 of 6 trivalent inactivated influenza vaccine (TIV)‐controlled and 14 placebo‐controlled studies, respectively; 3212 children were revaccinated in year 2 of 4 placebo‐controlled studies. Compared with placebo for days 0–10 post‐vaccination, LAIV recipients exhibited increased runny/stuffy nose (+7%), headache (+7%), and tiredness/decreased activity (+2%) after dose 1; and a higher rate of decreased appetite (+4%) after year 2 revaccination. Compared with TIV, only runny/stuffy nose was increased (dose 1, +12%; dose 2, +4%). Compared with initial vaccination, LAIV reactogenicity was lower after dose 2 in year 1 and revaccination in year 2. Unsolicited adverse events (AEs) increased with LAIV in some comparisons were headache, nasal congestion/rhinorrhea, rhinitis, and pyrexia; ear pain and lower respiratory illness were decreased. There was no evidence of an increase in any potential vaccine‐related serious AE in LAIV recipients. Among children aged 2–17 years and specifically aged 24–35 months, there was no evidence that lower respiratory illness or wheezing illness occurred at a higher rate in LAIV recipients. Conclusion This analysis supports the safety of Ann Arbor strain LAIV in children aged 2–17 years and provides a consensus assessment of events expected after vaccination.     

Patients with history of covid-19 had more side effects after the first dose of covid-19 vaccine

IntroductionCOVID-19 vaccination seems to be the most pertinent pharmacologic public health measure to control the pandemic. Reactogenicity symptoms were frequent in vaccine recipients mostly mild to moderate and commonly reported after the second dose. However, there is a lack of data in patients with a previous diagnosis of Covid-19.MethodsWe analysed side effects of 311 patients after the first dose of Pfizer-BioNTech COVID-19 vaccine, in a french university hospital. We compared patients with COVID-19 history to naive individuals. All the data collected are based on self-reported, including COVID-19 exposure status.ResultsOverall, 229 (74%) patients reported at least one side effect. Among participants with history of Covid-19, 95% reported at least one adverse event versus 70% in naive patients (p < 0.01). However, symptom intensity was not different between the 2 groups.ConclusionVaccine recipients with prior COVID-19 reported more, but no more serious, side effects than naive participants.