Clearly Defining Re-exposure Protection And Vaccine Efficacy Statistical Results

Publications often discuss how vaccines / prior infections may result in future protection from a virus. For example, a recent publication stated "83% protection" after recovering from a primary viral infection. Is a "pragmatically useful" number higher or lower? And what does the number mean? This depends on what is meant by "protection" and the data used in determination of the number.It is well accepted that immune response (not necessarily viral damage) often causes headaches, myalgia, and fatigue, (even chills/fever). Recently approved mRNA vaccines (which involve only Spike protein and no infectious viral aspect) stimulate immune response and may present these symptoms. How are "symptomatic" cases defined? Are they symptoms unique to viral damage like sore throat, congestion, cough? Or should brief symptoms solely related to immune response be included in the definition?Are asymptomatic infections [properly] categorized as a protective result?What PCR Ct defines "infection"? How should high Ct count / borderline positive / essentially non-shedding tests be categorized?It is proposed that Ct counts be grouped into categories of "strongly shedding", "moderately shedding", "borderline positive / lightly shedding", and "negative". These categories could identify a clinically useful spectrum of PCR "positive-ness". Further, it may be reasonable to assume that viable virus is likely when Ct counts are low, but not necessarily with borderline positive Ct counts. PCR tests detect viral RNA presence, but do not indicate virus viability. Serious cases that result in hospital admission could be a category that would help identify the level of "protection", or lack thereof.If, for example, only 15 of 44 people with "positive" PCR indications are found symptomatic, is it appropriate to use the 15 or the 44 in determining the statistical statement of "protection"? And should brief headache / myalgia with no sore throat, cough, congestion be considered "symptomatic" even though it may just be a rapid secondary immune response to re-exposure? Does PCR Ct count suggest significant shedding indicating MMID similarity ?It is proposed that studies should use improved definitions to specify categories when discussing "protection" and "efficacy". The most important indications for "protection" might include:•What is the "class" of symptom characteristics?•Is there significant virally caused tissue damage?•Is there significant shedding?•Did hospital admission occur?It is important to state statistical study observations across a set of categorical interpretations. And popular press should respectfully convey the statistics and definitions.

Evaluation of age-related distribution of measles cases with primary and secondary immune response in Russian Federation, 2010-2016

In 2010—2016, blood serum samples were examined from 5539 patients, aged < 1—60 years, with clinically and laboratory confirmed measles. Primary or secondary type of immune response was determined for all measles cases. Studies were performed with children aged < 1—14 years (2381), adolescents, 15—17 years old (189), and adults aged 18—60 years (2969). Serum measles-specific IgM antibodies were measured by “VektoKor’ IgM” ELISA test system (Russia), concentration and avidity of specific IgG — by using “Anti-Measles Viruses ELISA/IgG” and “Avidity: Anti-Measles Viruses ELISA/ IgG” (Euroimmun, Germany). Primary immune response was identified based on the presence of serum measles-specific low avidity IgM and IgG antibodies, whereas secondary immune response was characterized by detecting high avidity IgM and IgG antibodies at concentration of ≥ 5.0 IU/ml. Analyzing measles-specific IgM antibodies in 2010—2016 demonstrated that measles morbidity was mainly due to children, aged 1—2 years reaching up to 39.9% of the total number of children with measles aged < 1—14 years as well as adults aged 18—40 years old comprising as high as 80.1% total number of patients aged 15—60 years. Serum measles-specific IgG testing showed that in 15.0% of cases they were detected at concentration of ≥ 5.0 IU/ml. Further serum dilution resulted in finding IgG titer ranging within 8.5—45.0 IU/ml (21.4+0.36) and high avidity antibodies in 80—100% (92.5+0.2) cases. The remaining 85.0% cases found low avidity measles-specific IgG antibodies (< 30%) at concentration of 0.2—3.46 IU/ml (1.73+0.03). An age-related analysis of our data demonstrated that all children under 14 with laboratory-confirmed measles developed primary immune response. Moreover, in 73.7% of measles patients aged 15—60 with primary immune response measles might be prevented by timely vaccination, whereas persons with “vaccine failure” comprised 26.3%. In 2010 (0.09 per 100,000 subjects) and 2016 (0.12 per 100,000 subjects), frequency of patients with “vaccine failure” during relative epidemic well-being was 35.3% and 18.2%, respectively, exceeding 9.9% (p < 0.001) serving as a hallmark 2014 high measles incidence rate (3.24 per 100,000 subjects).The data obtained indicate that measles virus circulate among people with “vaccine failure,” which may account for potential to spread and infect unprotected population cohorts as well as cause measles outbreaks during periods of epidemic well-being.

Paraquat Preferentially Induces Apoptosis of Late Stage Effector Lymphocyte and Impairs Memory Immune Response in Mice

Paraquat (PQ) is a toxic non-selective herbicide. To date, the effect of PQ on memory immune response is still unknown. We investigated the impact of PQ on memory immune response. Adult C57BL/6 mice were subcutaneously injected with 2 mg/kg PQ, 20 mg/kg PQ or vehicle control every three days for two weeks. A single injection of keyhole limpet hemocyanin (KLH) at day four after the initial PQ treatment was used to induce a primary immune response; a second KLH challenge was performed at three months post the first KLH immunization to induce a secondary immune response. In steady state, treatment with 20 mg/kg PQ reduced the level of serum total IgG, but not that of IgM; treatment with 20 mg/kg PQ decreased the number of effector and memory lymphocytes, but not naïve or inactivated lymphocytes. During the primary immune response to KLH, treatment with 20 mg/kg PQ did not influence the proliferation of lymphocytes or expression of co-stimulatory molecules. Instead, treatment with 20 mg/kg PQ increased the apoptosis of lymphocytes at late stage, but not early stage of the primary immune response. During the secondary immune response to KLH, treatment with 20 mg/kg PQ reduced the serum anti-KLH IgG and KLH-responsive CD4 T cells and B cells. Moreover, effector or activated lymphocytes were more sensitive to PQ-induced apoptosis in vitro. Treatment with 2 mg/kg PQ did not impact memory immune response to KLH. Thus, treatment with 20 mg/kg PQ increased apoptosis of late stage effector cells to yield less memory cells and thereafter impair memory immune response, providing a novel understanding of the immunotoxicity of PQ.