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.

Quality health care rests fundamentally on the achievements of biomedical research. All health outcomes are improved by sound science: health status can be turned around by transplantation when someone's life is in jeopardy due to a diseased organ; social functioning can be improved by shock wave lithotripsy that -leads to faster recovery; and satisfaction can beenhanced when children with moderate or severe asthma receive appropriate anti-inflammatory treatment. To improve the quality of health care that patients actually receive, both biomedical research production and especially its introduction into clinical practice need to be examined.

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Managing Clinical Knowledge for Health Care Improvement

Antibody response to influenza vaccination in the elderly: a quantitative review.

Background
Different types of influenza vaccines are currently produced worldwide. Healthy adults are presently targeted mainly in North America.

Objectives
Identify, retrieve and assess all studies evaluating the effects of vaccines against influenza in healthy adults.

Search methods
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2010, issue 2), MEDLINE (January 1966 to June 2010) and EMBASE (1990 to June 2010).

Selection criteria
Randomised controlled trials (RCTs) or quasi-RCTs comparing influenza vaccines with placebo or no intervention in naturally-occurring influenza in healthy individuals aged 16 to 65 years. We also included comparative studies assessing serious and rare harms.

Data collection and analysis
Two review authors independently assessed trial quality and extracted data.

Main results
We included 50 reports. Forty (59 sub-studies) were clinical trials of over 70,000 people. Eight were comparative non-RCTs and assessed serious harms. Two were reports of harms which could not be introduced in the data analysis. In the relatively uncommon circumstance of vaccine matching the viral circulating strain and high circulation, 4% of unvaccinated people versus 1% of vaccinated people developed influenza symptoms (risk difference (RD) 3%, 95% confidence interval (CI) 2% to 5%). The corresponding figures for poor vaccine matching were 2% and 1% (RD 1, 95% CI 0% to 3%). These differences were not likely to be due to chance. Vaccination had a modest effect on time off work and had no effect on hospital admissions or complication rates. Inactivated vaccines caused local harms and an estimated 1.6 additional cases of Guillain-Barre Syndrome per million vaccinations. The harms evidence base is limited.

Authors' conclusions
Influenza vaccines have a modest effect in reducing influenza symptoms and working days lost. There is no evidence that they affect complications, such as pneumonia, or transmission.

WARNING:
This review includes 15 out of 36 trials funded by industry (four had no funding declaration). An earlier systematic review of 274 influenza vaccine studies published up to 2007 found industry funded studies were published in more prestigious journals and cited more than other studies independently from methodological quality and size. Studies funded from public sources were significantly less likely to report conclusions favorable to the vaccines. The review showed that reliable evidence on influenza vaccines is thin but there is evidence of widespread manipulation of conclusions and spurious notoriety of the studies. The content and conclusions of this review should be interpreted in light of this finding.

Vaccines for preventing influenza in healthy adults

The intranasal inoculation of volunteers with living partially attenuated strains of influenza A and B viruses offers a new opportunity to determine the protective effect of serum haemagglutin-inhibiting antibody against a strictly homologous virus, under conditions where the time and dosage of the infective challenge can be controlled, the scoring of proven infections can be more precise and higher rates of infection can be achieved than in most natural epidemics.In 1032 adult volunteers, whose serum HI antibody titre was determined immediately before virus challenge, there was a consistent inverse quantitative relationship between the HI titre and the likelihood of infection. The PD 50 (50% protective dose) of HI antibody was 1/18-1/36, but an unusual finding was that volunteers with no detectable pre-challenge antibody often seem to be less susceptible to infection than those with pre-challenge antibody in low titre.In one group of volunteers challenged with an influenza B strain there was no evidence that pre-challenge antibody titres against viral neuraminidase had any significant protective effect against challenge infection.

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The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses.

Effect of influenza vaccines in stimulating antibody in volunteers with prior immunity.

A comparison of live and killed influenza-virus vaccines. Report to the Medical Research Council's Committee on Influenza and other Respiratory Virus Vaccines.

Normal non-irradiated McCoy cell cultures provide a sensitive and reproducible method for the isolation of oculo-genital strains of chlamydia A directly from human secretions and for laboratory studies with these agents. Since September 1973, chlamydia have been isolated from 175 of 562 women (32-1%) attending venereal disease clinics. Freshly isolated and low passage strains have been used to determine the importance of centrifugation, constitution and pH of the tissue culture medium, and the temperature of incubation in controlling the efficiency of plating in the method.

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Factors affecting the sensitivity of replicating McCoy cells in the isolation and growth of chlamydia A (TRIC agents).

In this paper we describe our experience with a. live vaccine made from an influenza type B virus. Type B was chosen for a number of reasorls. We had had no previous experience with it, an attenuated virus with an acceptable passage history was available, and the low incidence of haemagglutination-inhibiting (HI) antibodies in the population was likely to make it easier to find susceptible volunteers than when an A virus was used. In addition, because different antigenic subtypes of influenza B circulate at the saxnel time (Coinmunicable Disease Center Report, 1965) we wished to look at the evidence for cross-protection. We a]so wished to assess the importance of repeated vaccinatiorls, on which some Russian workers lay considerable stress (SmorodintseJv et al., 1965). Previous trials of live influerlza vaccines in Great Britain (in which repeated vaccinations had not been given) had used vaccines made from a 1957 Russian A 2 virus (McDonald et al. 1 962; Andrews et al. 1 966; Beare et al. 1 967). The results showed that attenuated live viruses infected fairly readily when serum antibody was low or absent, that infection was followed by resistance to challenge with the sarne virus, and that there was a significant rise of antibody in a proportion of people.

D. Hobson

Papers

The role of serum haemagglutination-inhibiting antibody in protection against challenge infection with influenza A2 and B viruses.

Effect of influenza vaccines in stimulating antibody in volunteers with prior immunity.

A comparison of live and killed influenza-virus vaccines. Report to the Medical Research Council's Committee on Influenza and other Respiratory Virus Vaccines.

Factors affecting the sensitivity of replicating McCoy cells in the isolation and growth of chlamydia A (TRIC agents).

Live influenza B vaccine in volunteers. A report to the Medical Research Council by their Committee on Influenza and Other Respiratory Virus Vaccines.