Background Vaccines are needed to prevent coronavirus disease 2019 (Covid-19) and to protect persons who are at high risk for complications. The mRNA-1273 vaccine is a lipid nanoparticle-encapsulated mRNA-based vaccine that encodes the prefusion stabilized full-length spike protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes Covid-19. Methods This phase 3 randomized, observer-blinded, placebo-controlled trial was conducted at 99 centers across the United States. Persons at high risk for SARS-CoV-2 infection or its complications were randomly assigned in a 1:1 ratio to receive two intramuscular injections of mRNA-1273 (100 μg) or placebo 28 days apart. The primary end point was prevention of Covid-19 illness with onset at least 14 days after the second injection in participants who had not previously been infected with SARS-CoV-2. Results The trial enrolled 30,420 volunteers who were randomly assigned in a 1:1 ratio to receive either vaccine or placebo (15,210 participants in each group). More than 96% of participants received both injections, and 2.2% had evidence (serologic, virologic, or both) of SARS-CoV-2 infection at baseline. Symptomatic Covid-19 illness was confirmed in 185 participants in the placebo group (56.5 per 1000 person-years; 95% confidence interval [CI], 48.7 to 65.3) and in 11 participants in the mRNA-1273 group (3.3 per 1000 person-years; 95% CI, 1.7 to 6.0); vaccine efficacy was 94.1% (95% CI, 89.3 to 96.8%; P Conclusions The mRNA-1273 vaccine showed 94.1% efficacy at preventing Covid-19 illness, including severe disease. Aside from transient local and systemic reactions, no safety concerns were identified. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; COVE ClinicalTrials.gov number, NCT04470427.).

https://www.nejm.org/doi/pdf/10.1056/NEJMoa2035389

Efficacy and Safety of the mRNA-1273 SARS-CoV-2 Vaccine.

Predictive models of immune protection from COVID-19 are urgently needed to identify correlates of protection to assist in the future deployment of vaccines. To address this, we analyzed the relationship between in vitro neutralization levels and the observed protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using data from seven current vaccines and from convalescent cohorts. We estimated the neutralization level for 50% protection against detectable SARS-CoV-2 infection to be 20.2% of the mean convalescent level (95% confidence interval (CI) = 14.4–28.4%). The estimated neutralization level required for 50% protection from severe infection was significantly lower (3% of the mean convalescent level; 95% CI = 0.7–13%, P = 0.0004). Modeling of the decay of the neutralization titer over the first 250 d after immunization predicts that a significant loss in protection from SARS-CoV-2 infection will occur, although protection from severe disease should be largely retained. Neutralization titers against some SARS-CoV-2 variants of concern are reduced compared with the vaccine strain, and our model predicts the relationship between neutralization and efficacy against viral variants. Here, we show that neutralization level is highly predictive of immune protection, and provide an evidence-based model of SARS-CoV-2 immune protection that will assist in developing vaccine strategies to control the future trajectory of the pandemic. Estimates of the levels of neutralizing antibodies necessary for protection against symptomatic SARS-CoV-2 or severe COVID-19 are a fraction of the mean level in convalescent serum and will be useful in guiding vaccine rollouts.

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Neutralizing antibody levels are highly predictive of immune protection from symptomatic SARS-CoV-2 infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in late 2019 in China and is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. To mitigate the effects of the virus on public health, the economy and society, a vaccine is urgently needed. Here I review the development of vaccines against SARS-CoV-2. Development was initiated when the genetic sequence of the virus became available in early January 2020, and has moved at an unprecedented speed: a phase I trial started in March 2020 and there are currently more than 180 vaccines at various stages of development. Data from phase I and phase II trials are already available for several vaccine candidates, and many have moved into phase III trials. The data available so far suggest that effective and safe vaccines might become available within months, rather than years. The development of vaccines against SARS-CoV-2 is reviewed, including an overview of the development process, the different types of vaccine candidate, and data from animal studies as well as phase I and II clinical trials in humans.

/pdf/sars-cov-2-vaccines-in-development-31fwfnvrk5.pdf

SARS-CoV-2 vaccines in development.

Immunology of COVID-19: Current State of the Science.

Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial.

Objective
To understand the distributions of DNA and neutralizing antibodies of human papillomavirus (HPV)16, 18 in 18-45 year-old women.


Methods
Totally, 1 494 women were enrolled through multistage random sampling in Funing, Jiangsu province. Cervical exfoliated cells were collected from them for HPV DNA testing, and serum samples were taken from them for the detection of HPV16, 18 neutralizing antibodies by using pseudovirion-based neutralization assay(PBNA).


Results
Among the 1 494 women, 28(1.9%) and 188(12.6%) were positive for DNA and neutralizing antibody of HPV16 respectively, and 15(1.0%) and 60(4.0%) were positive for DNA and neutralizing antibody of HPV18, respectively. There were no significant differences in the detection rates of DNA and neutralizing antibody of HPV16, 18 among different age groups. About 16.7% of the women were infected with HPV16, 18, or both.


Conclusion
In Funing county of Jiangsu province, most women aged 18-45 years has no immunity to HPV16 and 18, indicating that they are appropriate targets for HPV 16/18 vaccination.


Key words: 
Human papillomavirus; Neutralizing antibody; Pseudovirion-based neutralization assay; Genotype; Prevalence

[Detection of neutralizing antibodies and DNA of human papillomavirus 16, 18 in women aged 18-45 years in Funing, Jiangsu province].

The invention discloses a mercury thermometer standardization groove, which comprises a test tube frame with a hemisphere-shaped appearance. The hemispherical surface of the test tube frame is provided with multiple slots; the slots are internally provided with radial tube holes; the top part of the slots is provided with a standard hole; temperature measuring ends of the tube holes are concentrated in a local small spherical area; and the bottom part of the tube holes is provided with a base. By adopting the hemisphere-shaped design, to-be-standardized thermometers are inserted in the inner radial tube holes, the bottom parts of the tube holes are concentrated towards the center position of the hemisphere, the temperature measuring ends of all thermometers are ensured to be concentrated in a small area, the problem of different temperature at a different position of a water bath box is avoided, the temperature measurement is more accurate, and errors can be eliminated easily.

Mercury thermometer standardization groove

Head-to-head immunogenicity comparison of an Escherichia coli-produced 9-valent human papillomavirus vaccine and Gardasil 9 in women aged 18-26 years in China: a randomised blinded clinical trial.

Objective: To assess the immunogenicity and safety of a booster vaccination with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: The phase Ⅱ trial of an inactivated SARS-CoV-2 vaccine was conducted by Jiangsu Provincial Center for Disease Control and Prevention (CDC) since October 2020. The subjects were healthy adults aged 18-59 years, excluding pregnant, and not breastfeeding women. The primary vaccination schedule groups were 0-14 d 5 μg, 0-14 d 10 μg, 0-28 d 5 μg and 0-28 d 10 μg, respectively. And 50 participants in each group, a total of 200, who have received 2-doses primary vaccination were selected in ascending order of the study number and vaccinated with a booster dose (same dosage as primary vaccination) at the 6th months after post the primary vaccination (30-day window period). Blood samples were collected before and after boosting and tested for the geometric mean titers (GMT) and seroconversion of live virus neutralizing antibody, pseudovirus neutralizing antibody and receptor-binding-domain (RBD) IgG antibody. Adverse events (AE) were collected and assessed within 28 days after boosting. Results: The ages of subjects in group 0-14 d 5 μg, 0-14 d 10 μg, 0-28 d 5 μg and 0-28 d 10 μg were (43.98±9.58), (43.46±9.34), (42.56±9.08) and (43.94±11.05) years old, respectively (P=0.877). Sex ratios were balanced among the 4 groups (P=0.331). The live virus neutralizing antibody GMT (95%CI) in group 0-14 d 5 μg, 0-14 d 10 μg, 0-28 d 5 μg and 0-28 d 10 μg increased from 4.07 (3.30-5.04), 3.75 (3.08-4.55), 8.33 (7.01-11.11) and 7.69 (6.19-9.57) before the booster vaccination to 284.84 (215.28-376.86), 233.05 (178.61-304.08), 274.81 (223.64-337.68) and 280.77 (234.59-336.04) in 28 days after the booster vaccination, respectively. The rates of live virus neutralizing antibody seroconversion were all 100% in the 4 groups. The AE incidences following booster vaccination were 18.0% (9 cases), 4.0% (2 cases), 12% (6 cases), and 12% (6 cases) in the 4 groups(P=0.182). No AE was graded as level 3 or worse. No serious AE was reported. Conclusion: One booster vaccination of an inactivated SARS-CoV-2 vaccine administered 6 months after primary vaccination showed good immunogenicity and safety.

[Immunogenicity and safety of a booster vaccination with an inactivated severe acute respiratory syndrome coronavirus 2 vaccine in adults aged 18 to 59 years].

Objective: To assess the immunogenicity and safety of a booster vaccination with an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine. Methods: The phase Ⅱ trial of an inactivated SARS-CoV-2 vaccine was conducted by Jiangsu Provincial Center for Disease Control and Prevention (CDC) since October 2020. The subjects were healthy adults aged 18-59 years, not pregnant, and not breastfeeding. The primary vaccination schedule groups were 0-14 d 5 μg, 0-14 d 10 μg, 0-28 d 5 μg and 0-28 d 10 μg, respectively. And 50 participants in each group, a total of 200, who have received 2-doses primary vaccination were selected in ascending order of the study number and vaccinated with a booster dose (same dosage as primary vaccination) 6 months post the primary vaccination (30-day window period). Blood samples were collected before and after boosting and tested for the geometric mean titers (GMT) and seroconversion of live virus neutralizing antibody, pseudovirus neutralizing antibody and receptor-binding-domain (RBD) IgG antibody. Adverse event (AE) was collected and assessed within 28 days after boosting. Results: The ages of subjects in group 0-14 d 5 μg, 0-14 d 10 μg, 0-28 d 5 μg and 0-28 d 10 μg were (43.98±9.58), (43.46±9.34), (42.56±9.08) and (43.94±11.05) years old, respectively (P=0.877). Sex ratio were balanced among the 4 groups (P=0.331). The live virus neutralizing antibody GMT (95%CI) in group 0-14 d 5 μg, 0-14 d 10 μg, 0-28 d 5 μg and 0-28 d 10 μg increased from 4.07 (3.30-5.04), 3.75 (3.08-4.55), 8.33 (7.01-11.11) and 7.69 (6.19-9.57) before the booster vaccination to 284.84 (215.28-376.86), 233.05 (178.61-304.08), 274.81 (223.64-337.68) and 280.77 (234.59-336.04) 28 days after the booster vaccination, respectively. Live virus neutralizing antibody seroconversion were all 100% in the 4 groups. The AE incidences following booster vaccination were 18.0% (9 cases), 4.0% (2 cases), 12% (6 cases), and 12% (6 cases) in the 4 groups. No AE was graded as level 3 or worsen. No serious AE was reported. Conclusion: One booster vaccination of an inactivated SARS-CoV-2 vaccine administered 6 months after primary vaccination showed good immunogenicity and safety.

[Immunogenicity and safety of a booster vaccination with an inactivated severe acute respiratory syndrome coronavirus 2 vaccine in adults aged 18 to 59 years old].

Kai Chu

Papers

[Detection of neutralizing antibodies and DNA of human papillomavirus 16, 18 in women aged 18-45 years in Funing, Jiangsu province].

Mercury thermometer standardization groove

Head-to-head immunogenicity comparison of an Escherichia coli-produced 9-valent human papillomavirus vaccine and Gardasil 9 in women aged 18-26 years in China: a randomised blinded clinical trial.

[Immunogenicity and safety of a booster vaccination with an inactivated severe acute respiratory syndrome coronavirus 2 vaccine in adults aged 18 to 59 years].

[Immunogenicity and safety of a booster vaccination with an inactivated severe acute respiratory syndrome coronavirus 2 vaccine in adults aged 18 to 59 years old].