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Background We assessed associations between binding antibody (bAb) concentration <5 days from symptom onset and testing positive for COVID-19 among patients in a test-negative study. Methods From October 2021 to June 2022, study sites in 7 states enrolled patients aged ≥6 months presenting with acute respiratory illness. Respiratory specimens were tested for SARS-CoV-2. In blood specimens, we measured concentrations of anti-SARS-CoV-2 antibodies against the spike protein receptor binding domain (RBD) and nucleocapsid antigens from the ancestral strain in standardized bAb units (BAU). Percentage change in odds of COVID-19 by increasing anti-RBD bAb was estimated via logistic regression as (1 – adjusted odds ratio of COVID-19) × 100, adjusting for COVID-19 mRNA vaccine doses, age, site, and high-risk exposure. Results Out of 2018 symptomatic patients, 662 (33%) tested positive for acute SARS-CoV-2 infection. Geometric mean RBD bAb levels were lower among COVID-19 cases than SARS-CoV-2 test-negative controls during the Delta-predominant period (112 vs 498 BAU/mL) and Omicron-predominant period (823 vs 1189 BAU/mL). Acute-phase ancestral spike RBD bAb levels associated with 50% lower odds of COVID-19 were 1968 BAU/mL against Delta and 3375 BAU/mL against Omicron; thresholds may differ in other laboratories. Conclusions During acute illness, antibody concentrations against ancestral spike RBD were associated with protection against COVID-19. [ABSTRACT FROM AUTHOR]

Evaluations of vaccine effectiveness (VE) are important to monitor as coronavirus disease 2019 (COVID-19) vaccines are introduced in the general population. Research staff enrolled symptomatic participants seeking outpatient medical care for COVID-19-like illness or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing from a multisite network. VE was evaluated using the test-negative design. Among 236 SARS-CoV-2 nucleic acid amplification test-positive and 576 test-negative participants aged ≥16 years, the VE of messenger RNA vaccines against COVID-19 was 91% (95% confidence interval, 83%-95%) for full vaccination and 75% (55%-87%) for partial vaccination. Vaccination was associated with prevention of most COVID-19 cases among people seeking outpatient medical care. [ABSTRACT FROM AUTHOR]

Background: Preexisting antibodies to influenza, shaped by early infection and subsequent exposures, may impact responses to influenza vaccination.Methods: We enrolled 72 children (aged 7-17 years) in 2015-2016; all received inactivated influenza vaccines. Forty-one were also vaccinated in 2014-2015, with 12 becoming infected with A(H3N2) in 2014-2015. Thirty-one children did not have documented influenza exposures in the prior 5 seasons. Sera were collected pre- and postvaccination in both seasons. We constructed antibody landscapes using hemagglutination inhibition antibody titers against 16 A(H3N2) viruses representative of major antigenic clusters that circulated between 1968 and 2015.Results: The breadth of the antibody landscapes increased with age. Vaccine-induced antibody responses correlated with boosting of titers to previously encountered antigens. Postvaccination titers were the highest against vaccine antigens rather than the historic A(H3N2) viruses previously encountered. Prevaccination titers to the vaccine were the strongest predictors of postvaccination titers. Responses to vaccine antigens did not differ by likely priming virus. Influenza A(H3N2)-infected children in 2014-2015 had narrower antibody landscapes than those uninfected, but prior season infection status had little effect on antibody landscapes following 2015-2016 vaccination.Conclusions: A(H3N2) antibody landscapes in children were largely determined by age-related immune priming, rather than recent vaccination or infection. [ABSTRACT FROM AUTHOR]

Background: Increased illness due to antigenically drifted A(H3N2) clade 3C.3a influenza viruses prompted concerns about vaccine effectiveness (VE) and vaccine strain selection. We used US virologic surveillance and US Influenza Vaccine Effectiveness (Flu VE) Network data to evaluate consequences of this clade.Methods: Distribution of influenza viruses was described using virologic surveillance data. The Flu VE Network enrolled ambulatory care patients aged ≥6 months with acute respiratory illness at 5 sites. Respiratory specimens were tested for influenza by means of reverse-transcriptase polymerase chain reaction and were sequenced. Using a test-negative design, we estimated VE, comparing the odds of influenza among vaccinated versus unvaccinated participants.Results: During the 2018-2019 influenza season, A(H3N2) clade 3C.3a viruses caused an increasing proportion of influenza cases. Among 2763 Flu VE Network case patients, 1325 (48%) were infected with A(H1N1)pdm09 and 1350 (49%) with A(H3N2); clade 3C.3a accounted for 977 (93%) of 1054 sequenced A(H3N2) viruses. VE was 44% (95% confidence interval, 37%-51%) against A(H1N1)pdm09 and 9% (-4% to 20%) against A(H3N2); VE was 5% (-10% to 19%) against A(H3N2) clade 3C.3a viruses.Conclusions: The predominance of A(H3N2) clade 3C.3a viruses during the latter part of the 2018-2019 season was associated with decreased VE, supporting the A(H3N2) vaccine component update for 2019-2020 northern hemisphere influenza vaccines. [ABSTRACT FROM AUTHOR]

Background: The effectiveness of influenza vaccine during 2015-2016 was reduced in some age groups as compared to that in previous 2009 pandemic influenza A(H1N1) virus (A[H1N1]pdm09 virus)-predominant seasons. We hypothesized that the age at first exposure to specific influenza A(H1N1) viruses could influence vaccine effectiveness (VE).Methods: We estimated the effectiveness of influenza vaccine against polymerase chain reaction-confirmed influenza A(H1N1)pdm09-associated medically attended illness from the 2010-2011 season through the 2015-2016 season, according to patient birth cohort using data from the Influenza Vaccine Effectiveness Network. Birth cohorts were defined a priori on the basis of likely immunologic priming with groups of influenza A(H1N1) viruses that circulated during 1918-2015. VE was calculated as 100 × [1 - adjusted odds ratio] from logistic regression models comparing the odds of vaccination among influenza virus-positive versus influenza test-negative patients.Results: A total of 2115 A(H1N1)pdm09 virus-positive and 14 696 influenza virus-negative patients aged ≥6 months were included. VE was 61% (95% confidence interval [CI], 56%-66%) against A(H1N1)pdm09-associated illness during the 2010-2011 through 2013-2014 seasons, compared with 47% (95% CI, 36%-56%) during 2015-2016. During 2015-2016, A(H1N1)pdm09-specific VE was 22% (95% CI, -7%-43%) among adults born during 1958-1979 versus 61% (95% CI, 54%-66%) for all other birth cohorts combined.Conclusion: Findings suggest an association between reduced VE against influenza A(H1N1)pdm09-related illness during 2015-2016 and early exposure to specific influenza A(H1N1) viruses. [ABSTRACT FROM AUTHOR]

The article presents the author's views on influenza vaccine effectiveness (VE) based on antigenic matching of the vaccine and the virus. He cites the study by Skowronski et al. that highlights the importance of factors beyond antigenic matching of VE with lineage virus. He explains that VE can vary by subtype/lineage, genetic clade, product type, and vaccination status, but the mechanisms involving host immune response, virus characteristics, and vaccine composition remain poorly understood.

Background: Two doses of measles, mumps, and rubella (MMR) vaccine are 97% effective against measles, but waning antibody immunity to measles and failure of the 2-dose vaccine occur. We administered a third MMR dose (MMR3) to young adults and assessed immunogenicity over 1 year.Methods: Measles virus (MeV) neutralizing antibody concentrations, cell-mediated immunity (CMI), and immunoglobulin G (IgG) antibody avidity were assessed at baseline and 1 month and 1 year after MMR3 receipt.Results: Of 662 subjects at baseline, 1 (0.2%) was seronegative for MeV-neutralizing antibodies (level, <8 mIU/mL), and 23 (3.5%) had low antibody levels (8-120 mIU/mL). One month after MMR3 receipt, 1 subject (0.2%) was seronegative, and 6 (0.9%) had low neutralizing antibodies, with only 21 of 662 (3.2%) showing a ≥ 4-fold rise in neutralizing antibodies. One year after MMR3 receipt, no subject was seronegative, and 10 of 617 (1.6%) had low neutralizing antibody levels. CMI analyses showed low levels of spot-forming cells after stimulation, suggesting the presence of T-cell memory, but the response was minimal after MMR3 receipt. MeV IgG avidity did not correlate with findings of neutralization analyses.Conclusions: Most subjects were seropositive before MMR3 receipt, and very few had a secondary immune response after MMR3 receipt. Similarly, CMI and avidity analyses showed minimal qualitative improvements in immune response after MMR3 receipt. We did not find compelling data to support a routine third dose of MMR vaccine. [ABSTRACT FROM AUTHOR]

Background. The 2009 influenza A virus subtype H1N1 (A[H1N1]pdm09) did not exhibit antigenic drift during the 2010-2011 influenza season, providing an opportunity to investigate the duration of protection after vaccination. We estimated the independent effects of 2010-2011 seasonal trivalent inactivated influenza vaccine (TIV) and A(H1N1)pdm09 vaccine for preventing medically attended influenza A virus infection during the 2010-2011 season. Methods. Individuals were tested for influenza A virus by real-time reverse transcription polymerase chain reaction (rRT-PCR) after a clinical encounter for acute respiratory illness. Case-control analyses compared participants with rRT-PCR-confirmed influenza A virus infection and test-negative controls. Vaccine effectiveness was estimated separately for monovalent pandemic vaccine and TIV and was calculated as 100 x [1 - adjusted odds ratio], where the odds ratio was adjusted for potential confounders. Results. The effectiveness of TIV against influenza A virus infection was 63% (95% confidence interval [CI], 37%-78%). The effectiveness of TIV against A(H1N1)pdm09 infection was 77% (95% CI, 44%-90%). Monovalent vaccine administered between October 2009 and April 2010 was not protective during the 2010-2011 season, with an effectiveness of -1% (95% CI, -146% to 59%) against A(H1N1)pdm09 infection. Conclusions. Monovalent vaccine provided no sustained protection against A(H1N1)pdm09 infection during the 2010-2011 season. This waning effectiveness supports the need for annual revaccination, even in the absence of antigenic drift in A(H1N1)pdm09. [ABSTRACT FROM AUTHOR]

An outbreak of Escherichia coli 0157:H7 hemorrhagic colitis at a Minnesota junior high school in October 1988 comprised 32 cases among 1562 students (attack rate, 2.0%). Four children were hospitalized; none developed hemolytic-uremic syndrome. Case children were more likely than controls to have eaten heat-processed meat patties (odds ratio, 6.2; 95% confidence interval, 2.0–20.1; P < .001) in the school cafeteria on a specific day. The minimum estimated attack rate among students who ate these patties was 8%. The patties should have been sufficientlycooked by the manufacturer to destroy enteric pathogens before they were frozen and distributed. E. coli were cultured from frozen patties that were manufactured at the same plant on the same dates as the implicated patties, but serotype 0157:H7 was not isolated. Heat-processed meat patties may serve as vehicles for E. coli 0157:H7 infection, and currently there are no federal or state regulatory standards to ensure the safety of these products. [ABSTRACT FROM PUBLISHER]

A response from the author of the article is presented which discusses the estimation of the influenza vaccine effectiveness by using test-negative design and adjustment of the confounding factors.

Background: During the 2012-2013 influenza season, there was cocirculation of influenza A(H3N2) and 2 influenza B lineage viruses in the United States., Methods: Patients with acute cough illness for ≤7 days were prospectively enrolled and had swab samples obtained at outpatient clinics in 5 states. Influenza vaccination dates were confirmed by medical records. The vaccine effectiveness (VE) was estimated as [100% × (1 - adjusted odds ratio)] for vaccination in cases versus test-negative controls., Results: Influenza was detected in 2307 of 6452 patients (36%); 1292 (56%) had influenza A(H3N2), 582 (25%) had influenza B/Yamagata, and 303 (13%) had influenza B/Victoria. VE was 49% (95% confidence interval [CI], 43%-55%) overall, 39% (95% CI, 29%-47%) against influenza A(H3N2), 66% (95% CI, 58%-73%) against influenza B/Yamagata (vaccine lineage), and 51% (95% CI, 36%-63%) against influenza B/Victoria. VE against influenza A(H3N2) was highest among persons aged 50-64 years (52%; 95% CI, 33%-65%) and persons aged 6 months-8 years (51%; 95% CI, 32%-64%) and lowest among persons aged ≥65 years (11%; 95% CI, -41% to 43%). In younger age groups, there was evidence of residual protection from receipt of the 2011-2012 vaccine 1 year earlier., Conclusions: The 2012-2013 vaccines were moderately effective in most age groups. Cross-lineage protection and residual effects from prior vaccination were observed and warrant further investigation., (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.)