Vaccine-derived Immunity Research Articles

Bamlanivimab plus Etesevimab in Mild or Moderate Covid-19

BackgroundPatients with underlying medical conditions are at increased risk for severe coronavirus disease 2019 (Covid-19). Whereas vaccine-derived immunity develops over time, neutralizing monoclonal-antibody treatment provides immediate, passive immunity and may limit disease progression and complications.MethodsIn this phase 3 trial, we randomly assigned, in a 1:1 ratio, a cohort of ambulatory patients with mild or moderate Covid-19 who were at high risk for progression to severe disease to receive a single intravenous infusion of either a neutralizing monoclonal-antibody combination agent (2800 mg of bamlanivimab and 2800 mg of etesevimab, administered together) or placebo within 3 days after a laboratory diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. The primary outcome was the overall clinical status of the patients, defined as Covid-19–related hospitalization or death from any cause by day 29.ResultsA total of 1035 patients underwent randomization and received an infusion of bamlanivimab–etesevimab or placebo. The mean (±SD) age of the patients was 53.8±16.8 years, and 52.0% were adolescent girls or women. By day 29, a total of 11 of 518 patients (2.1%) in the bamlanivimab–etesevimab group had a Covid-19–related hospitalization or death from any cause, as compared with 36 of 517 patients (7.0%) in the placebo group (absolute risk difference, −4.8 percentage points; 95% confidence interval [CI], −7.4 to −2.3; relative risk difference, 70%; P<0.001). No deaths occurred in the bamlanivimab–etesevimab group; in the placebo group, 10 deaths occurred, 9 of which were designated by the trial investigators as Covid-19–related. At day 7, a greater reduction from baseline in the log viral load was observed among patients who received bamlanivimab plus etesevimab than among those who received placebo (difference from placebo in the change from baseline, −1.20; 95% CI, −1.46 to −0.94; P<0.001).ConclusionsAmong high-risk ambulatory patients, bamlanivimab plus etesevimab led to a lower incidence of Covid-19–related hospitalization and death than did placebo and accelerated the decline in the SARS-CoV-2 viral load. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.)

Global seroprevalence of SARS-CoV-2 antibodies: A systematic review and meta-analysis.

Many studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making. In this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634. We identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4-8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6% in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (p<0.001). National studies had lower seroprevalence estimates than regional and local studies (p<0.001). Compared to Caucasian persons, Black persons (prevalence ratio [RR] 3.37, 95% CI 2.64-4.29), Asian persons (RR 2.47, 95% CI 1.96-3.11), Indigenous persons (RR 5.47, 95% CI 1.01-32.6), and multi-racial persons (RR 1.89, 95% CI 1.60-2.24) were more likely to be seropositive. Seroprevalence was higher among people ages 18-64 compared to 65 and over (RR 1.27, 95% CI 1.11-1.45). Health care workers in contact with infected persons had a 2.10 times (95% CI 1.28-3.44) higher risk compared to health care workers without known contact. There was no difference in seroprevalence between sex groups. Seroprevalence estimates from national studies were a median 18.1 times (IQR 5.9-38.7) higher than the corresponding SARS-CoV-2 cumulative incidence, but there was large variation between Global Burden of Disease regions from 6.7 in South Asia to 602.5 in Sub-Saharan Africa. Notable methodological limitations of serosurveys included absent reporting of test information, no statistical correction for demographics or test sensitivity and specificity, use of non-probability sampling and use of non-representative sample frames. Most of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response.

Post-Vaccination Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infections and Incidence of the Presumptive B.1.427/B.1.429 Variant Among Healthcare Personnel at a Northern California Academic Medical Center.

BackgroundAlthough mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines report >90% efficacy, breakthrough infections occur. Little is known about their effectiveness against SARS-CoV-2 variants, including the highly prevalent B.1.427/B.1.429 variant.MethodsIn this quality improvement project, we collected demographic and clinical information from post-vaccine SARS-CoV-2 cases (PVSCs), defined as healthcare personnel (HCP) with positive SARS-CoV-2 nucleic acid amplification test after receiving ≥1 vaccine dose. Available specimens were tested for L452R, N501Y, and E484K mutations using reverse-transcription polymerase chain reaction. Mutation prevalence was compared among unvaccinated, early post-vaccinated (≤14 days after dose 1), partially vaccinated (positive test >14 days after dose 1 and <14 days after dose 2), and fully vaccinated (>14 days after dose 2) PVSCs.ResultsFrom December 2020 to April 2021, ≥23 090 HCP received ≥1 dose of an mRNA-based SARS-CoV-2 vaccine, and 660 HCP cases of SARS-CoV-2 occurred, of which 189 were PVSCs. Among the PVSCs, 114 (60.3%), 49 (25.9%), and 26 (13.8%) were early post-vaccination, partially vaccinated, and fully vaccinated, respectively. Of 261 available samples from vaccinated and unvaccinated HCP, 103 (39.5%), including 42 PVSCs (36.5%), had the L452R mutation presumptive of B.1.427/B.1.429. When adjusted for community prevalence of B.1.427/B.1.429, PVSCs did not have significantly elevated risk of B.1.427/B.1.429 compared with unvaccinated HCP.ConclusionsMost PVSCs occurred prior to expected onset of full, vaccine-derived immunity. Presumptive B.1.427/B.1.429 was not more prevalent in post-vaccine cases than in unvaccinated SARS-CoV-2 HCP. Continued infection control measures, particularly <14 days post-vaccination, and continued variant surveillance in PVSCs are imperative to control future SARS-CoV-2 surges.

The British SARS-CoV-2 Variant of Concern, B.1.1.7, Reveals Its Lethality

Several emerging SARS-CoV-2 variants of concern (VOCs) appear to have heightened infectivity and ability to evade natural or vaccine-derived immunity.

Will vaccine-derived protective immunity curtail COVID-19 variants in the US?

Multiple effective vaccines are currently being deployed to combat the COVID-19 pandemic, and are viewed as the major factor in marked reductions of disease burden in regions with moderate to high vaccination coverage. The effectiveness of COVID-19 vaccination programs is, however, significantly threatened by the emergence of new SARS-COV-2 variants that, in addition to being more transmissible than the wild-type (original) strain, may at least partially evade existing vaccines. A two-strain (one wild-type, one variant) and two-group (vaccinated or otherwise) mechanistic mathematical model is designed and used to assess the impact of the vaccine-induced cross-protective efficacy on the spread the COVID-19 pandemic in the United States. Rigorous analysis of the model shows that, in the absence of any co-circulating SARS-CoV-2 variant, the vaccine-derived herd immunity threshold needed to eliminate the wild-type strain can be achieved if 59% of the US population is fully-vaccinated with either the Pfizer or Moderna vaccine. This threshold increases to 76% if the wild-type strain is co-circulating with the Alpha variant (a SARS-CoV-2 variant that is 56% more transmissible than the wild-type strain). If the wild-type strain is co-circulating with the Delta variant (which is estimated to be 100% more transmissible than the wild-type strain), up to 82% of the US population needs to be vaccinated with either of the aforementioned vaccines to achieve the vaccine-derived herd immunity. Global sensitivity analysis of the model reveal the following four parameters as the most influential in driving the value of the reproduction number of the variant strain (hence, COVID-19 dynamics) in the US: (a) the infectiousness of the co-circulating SARS-CoV-2 variant, (b) the proportion of individuals fully vaccinated (using Pfizer or Moderna vaccine) against the wild-type strain, (c) the cross-protective efficacy the vaccines offer against the variant strain and (d) the modification parameter accounting for the reduced infectiousness of fully-vaccinated individuals experiencing breakthrough infection. Specifically, numerical simulations of the model show that future waves or surges of the COVID-19 pandemic can be prevented in the US if the two vaccines offer moderate level of cross-protection against the variant (at least 67%). This study further suggests that a new SARS-CoV-2 variant can cause a significant disease surge in the US if (i) the vaccine coverage against the wild-type strain is low (roughly <66%) (ii) the variant is much more transmissible (e.g., 100% more transmissible), than the wild-type strain, or (iii) the level of cross-protection offered by the vaccine is relatively low (e.g., less than 50%). A new SARS-CoV-2 variant will not cause such surge in the US if it is only moderately more transmissible (e.g., the Alpha variant, which is 56% more transmissible) than the wild-type strain, at least 66% of the population of the US is fully vaccinated, and the three vaccines being deployed in the US (Pfizer, Moderna, and Johnson & Johnson) offer a moderate level of cross-protection against the variant.

A Call for Caution in Use of Pertussis Vaccine Effectiveness Studies to Estimate Waning Immunity: A Canadian Immunization Research Network Study.

Vaccine effectiveness (VE) studies provide essential evidence on waning vaccine-derived immunity, a major threat to pertussis control. We evaluated how study design affects estimates by comparing 2 case-control studies conducted in Ontario, Canada. We compared results from a test-negative design (TND) with a frequency-matched design (FMD) case-control study using pertussis cases from 2005-2015. In the first study, we identified test-negative controls from the public health laboratory that diagnosed cases and, in the second, randomly selected controls from patients attending the same physicians that reported cases, frequency matched on age and year. We compared characteristics of cases and controls using standardized differences. In both designs, VE estimates for the early years postimmunization were consistent with clinical trials (TND, 84%; FMD, 89% at 1-3 years postvaccination) but diverged as time since last vaccination increased (TND, 41%; FMD, 74% by 8 years postvaccination). Overall, we observed lower VE and faster waning in the TND than the FMD. In the TND but not FMD, controls differed from cases in important confounders, being younger, having more comorbidities, and higher healthcare use. Differences between the controls of each design were greater than differences between cases. TND controls were more likely to be unvaccinated or incompletely vaccinated than FMD controls (P < .001). The FMD adjusted better for healthcare-seeking behavior than the TND. Duration of protection from pertussis vaccines is unclear because estimates vary by study design. Caution should be exercised by experts, researchers, and decision makers when evaluating evidence on optimal timing of boosters.

The honeymoon period after mass vaccination.

Vaccination is an effective method to prevent individuals from contracting diseases like measles and the flu. Its success is clearly demonstrated by the large declines in the incidence of many diseases (e.g., childhood diseases like measles) after the start of mass vaccination programs. However, what happens after this drop in incidence can be complicated. It is known that some diseases exhibit "honeymoon periods" (long periods of temporary low disease incidence after start of mass vaccination). These periods end with a natural resurgence of the disease, which is not due to any change in the system. To study honeymoon periods, we used the compartmental model analyzed in [1] that can exhibit different types of vaccine failures: failure in degree (leakiness), in take (all-or-nothing) and in duration (waning of vaccine-derived immunity). We showed that traditional measures of transient dynamics in ecology may not distinguish between models with different honeymoon periods. We also provide a proof of global stability of the endemic equilibrium when the reproduction number (accounting for vaccination) is greater than one, and introduce a technical definition of the honeymoon period.

Susceptibility to Hepatitis A and B Virus Among Clients at a Syringe Services Program in Philadelphia, 2018.

Although many people who use drugs meet criteria for vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV), estimates of susceptibility (ie, lack of immunity) are not well established. This study sought to identify the prevalence of and characteristics associated with HAV and HBV susceptibility among people who use drugs attending an urban syringe services program. We initiated this seroprevalence study in 2018 among 438 clients of a syringe services program who met study criteria, including provision of a blood specimen and a self-reported history of drug use. We assessed HAV and HBV susceptibility and infection via serological testing. We examined associations between participant characteristics and serology status by using descriptive statistics and multivariable logistic regression models. Of the initial 438 clients identified, 353 (80.6%) met study criteria. Of 352 participants with conclusive HAV test results, 48.6% (n = 171) were HAV susceptible; of 337 participants with conclusive HBV test results, 32.6% (n = 110) were HBV susceptible, 24.3% (n = 82) showed evidence of past or present HBV infection, and 43.0% (n = 145) had vaccine-derived immunity. Compared with participants born before 1970, participants born during 1980-1989 had 5.90 (95% CI, 2.42-14.40) times the odds of HAV susceptibility and 0.18 (95% CI, 0.06-0.53) times the odds of HBV susceptibility, and participants born during 1990-1999 had 6.31 (95% CI, 2.34-17.00) times the odds of HAV susceptibility. Decreased odds of HAV susceptibility were associated with homelessness (adjusted odds ratio = 0.48; 95% CI, 0.28-0.82). Despite applicable HAV and HBV vaccination recommendations, substantial gaps exist in HAV and HBV susceptibility among a population of people who use drugs. These findings highlight the need for increased HAV and HBV vaccination efforts among people who use drugs.

Pre-existing yellow fever immunity impairs and modulates the antibody response to tick-borne encephalitis vaccination

Flaviviruses have an increasing global impact as arthropod-transmitted human pathogens, exemplified by Zika, dengue, yellow fever (YF), West Nile, Japanese encephalitis, and tick-borne encephalitis (TBE) viruses. Since all flaviviruses are antigenically related, they are prone to phenomena of immunological memory (‘original antigenic sin’), which can modulate immune responses in the course of sequential infections and/or vaccinations. In our study, we analyzed the influence of pre-existing YF vaccine-derived immunity on the antibody response to TBE vaccination. By comparing samples from YF pre-vaccinated and flavivirus–naive individuals, we show that YF immunity not only caused a significant impairment of the neutralizing antibody response to TBE vaccination but also a reduction of the specific TBE virus neutralizing activities (NT/ELISA-titer ratios). Our results point to a possible negative effect of pre-existing cross-reactive immunity on the outcome of flavivirus vaccination that may also pertain to other combinations of sequential flavivirus infections and/or vaccinations.

Role of Evolutionary Selection Acting on Vaccine Antigens in the Re-Emergence of Bordetella Pertussis.

Pertussis (“whooping cough”) is a re-emerging disease with increasing incidence among fully vaccinated individuals. We explored the genetic diversity of five Bordetella pertussis proteins used to generate the subunit vaccine across ancestral and newly emergent strains using immunoinformatics and evolutionary selection measurements. The five subunits of pertussis toxin (Ptx1–Ptx5) were highly conserved with regard to sequence, predicted structure, predicted antigenicity, and were under purifying selection. In contrast, the adhesin proteins pertactin (Prn) and filamentous hemagglutinin (FHA) were under statistically significant (p < 0.01) diversifying selection. Most heavily diversified sites of each protein fell within antigenic epitopes, and the functional adhesin motifs were conserved. Protein secondary structure was conserved despite sequence diversity for FHA but was changeable in Prn. These findings suggest that subunit vaccine-derived immunity does not impact Ptx1–Ptx5 but may apply evolutionary pressure to Prn and FHA to undergo diversifying selection. These findings offer further insight into the emergence of vaccine-resistant strains of B. pertussis.

Hepatitis B seroprevalence in 10-25-year-olds in Mexico - the 2012 national health and nutrition survey (ENSANUT) results

ABSTRACTObjectives: To estimate hepatitis B virus (HBV) seroprevalence from natural infection or vaccination in 10–25-year-olds in Mexico, using the 2012 National Health and Nutrition Survey (ENSANUT).Methods: Randomly selected serum samples (1,581) from adolescents and young adults, representative of 38,924,584 Mexicans, were analyzed to detect hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody (anti-HBc). Weighted HBV seroprevalence in the Mexican population and association with sociodemographic variables were calculated.Results: Overall weighted seroprevalence from natural infection (positive for anti-HBs and anti-HBc) was 0.23% (95% confidence interval [95% CI] 0.10–0.52). No HBsAg was detected, indicating no acute or chronic infection. Vaccine-derived immunity (positive ≥ 10.0 mIU/ml for anti-HBs and negative to anti-HBc) was 44.7% (95% CI: 40.2–49.4) overall; lower in persons aged 20–25 years (40.83%) than in persons aged 10–19 years (47.7%). Among the population analyzed, 54.2% (95% CI: 49.6–58.8) were seronegative to HBV (negative for all three markers) and no sociodemographic risk factors were identified.Conclusions: HBV seroprevalence from natural infection was low. Vaccination-induced immunity was higher among Mexican adolescents than young adults, possibly due to vaccination policies since 1999.

Updated NACI recommendations for measles post-exposure prophylaxis.

Human immune globulin (Ig) products are currently recommended as post-exposure prophylaxis (PEP) for measles in certain susceptible groups. However, successful measles vaccination programs in North America have led to low circulation of measles virus and most blood donors now have vaccine-derived immunity. Concurrently, the concentrations of anti-measles antibodies in human Ig products have shown trends of gradual decline and previously recommended doses and routes of administration may no longer be optimally protective. To review the literature and update recommendations on post-exposure prophylaxis for measles, including dosing and route of administration, for measles Ig PEP in susceptible infants and in individuals who are immunocompromised or pregnant, in order to prevent severe disease. The National Advisory Committee on Immunization (NACI) Measles, Mumps, Rubella, Varicella Working Group reviewed key literature, international practices, and product information for current Ig products pertaining to the optimal dosage and routes of Ig administration for measles PEP. It then proposed evidence-based changes to the PEP recommendations that were considered and approved by NACI. NACI continues to recommend that susceptible immunocompetent individuals six months of age and older, who are exposed to measles and who have no contraindications be given measles-mumps-rubella (MMR) vaccine within 72 hours of the exposure. NACI recommends that for susceptible infants younger than six months of age, if injection volume is not a major concern, intramuscular immunoglobulin (IMIg) should be provided at a concentration of 0.5 mL/kg, to a maximum dose of 15 mL administered over multiple injection sites. Susceptible infants six to 12 months old who are identified after 72 hours and within six days of measles exposure should receive IMIg (0.5 mL/kg) if injection volume is not a major concern. For susceptible contacts who are pregnant or immunocompromised, if injection volume is not a concern, IMIg can be provided at a concentration of 0.5 mL/kg understanding that recipients 30 kg or more will not receive the measles antibody concentrations that are considered to be fully protective. Alternatively, in cases where injection volume is a major concern or for recipients 30 kg or more, intravenous immunoglobulin (IVIg) can be provided at a dose of 400 mg/kg.NACI does not recommend that susceptible immunocompetent individuals older than 12 months of age receive Ig PEP for measles exposure due to the low risk of disease complications and the practical challenges of administration for case and contact management. NACI has updated the recommendations for measles PEP to reflect current evidence and best practices in order to prevent severe disease in Canada. Consistent with recommendations in other countries, this includes consideration of off-label use of IVIg in some instances.

Prolonging herd immunity to cholera via vaccination: Accounting for human mobility and waning vaccine effects.

BackgroundOral cholera vaccination is an approach to preventing outbreaks in at-risk settings and controlling cholera in endemic settings. However, vaccine-derived herd immunity may be short-lived due to interactions between human mobility and imperfect or waning vaccine efficacy. As the supply and utilization of oral cholera vaccines grows, critical questions related to herd immunity are emerging, including: who should be targeted; when should revaccination be performed; and why have cholera outbreaks occurred in recently vaccinated populations?Methods and findingsWe use mathematical models to simulate routine and mass oral cholera vaccination in populations with varying degrees of migration, transmission intensity, and vaccine coverage. We show that migration and waning vaccine efficacy strongly influence the duration of herd immunity while birth and death rates have relatively minimal impacts. As compared to either periodic mass vaccination or routine vaccination alone, a community could be protected longer by a blended “Mass and Maintain” strategy. We show that vaccination may be best targeted at populations with intermediate degrees of mobility as compared to communities with very high or very low population turnover. Using a case study of an internally displaced person camp in South Sudan which underwent high-coverage mass vaccination in 2014 and 2015, we show that waning vaccine direct effects and high population turnover rendered the camp over 80% susceptible at the time of the cholera outbreak beginning in October 2016.ConclusionsOral cholera vaccines can be powerful tools for quickly protecting a population for a period of time that depends critically on vaccine coverage, vaccine efficacy over time, and the rate of population turnover through human mobility. Due to waning herd immunity, epidemics in vaccinated communities are possible but become less likely through complementary interventions or data-driven revaccination strategies.

Vaccine waning and mumps re-emergence in the USA

BackgroundFollowing decades of declining mumps incidence amid widespread vaccination, the US has experienced a resurgence in mumps cases since 2006 driven largely by outbreaks on college campuses. The occurrence of cases among previously-vaccinated individuals and in communities with high vaccine coverage has prompted concerns about performance of the live attenuated mumps vaccine (Jeryl Lynn strain) currently included in the measles-mumps-rubella (MMR) series. It is unclear whether the resurgence is due to antigenic changes in circulating mumps virus, which would warrant consideration of a new vaccine, or to waning vaccine-derived protection, necessitating additional booster doses.MethodsWe pooled data from studies of vaccine effectiveness to test for waning of protection. We used mathematical models to measure changes in population immunity since mumps vaccine introduction and to assess whether recent mumps transmission dynamics are consistent with hypotheses of waning immunity or vaccine escape.ResultsWe estimate that vaccine-derived protection persists, on average, 29 (95% CI: 17–54) years after receipt of the last dose (Fig. 1). This waning accounts for 66.4% of unexplained variation in estimates of mumps vaccine effectiveness across published studies. Changes in age-specific susceptibility due to vaccine waning and declining transmission track with the current resurgence in cases among young adults in the USA, and explain outbreaks reported among vaccinated adolescents during the late 1980s (Fig. 2). In contrast, vaccine escape would not be expected to result in cases following the observed age distribution (Fig. 3). Routine adult booster vaccination is needed to sustain mumps elimination.ConclusionThe resurgence of mumps in the USA since 2006 is attributable to waning of vaccine-derived immunity, suggesting the need for booster doses in adulthood. Trials are needed to assess clinical protection afforded by booster doses in individuals with a history of MMR vaccination.Disclosures J. Lewnard, Pfier: Grant Investigator, Research grant

Vaccine impact in homogeneous and age-structured models

A general model of an imperfect vaccine for a childhood disease is presented and the effects of different types of vaccine failure on transmission were investigated using models that consider both homogeneous and age-specific mixing. The models are extensions of the standard SEIR equations with an additional vaccinated component that allows for five different vaccine parameters: three types of vaccine failure in decreasing susceptibility to infection via failure in degree ("leakiness"), take ("all-or-nothingness") and duration (waning of vaccine-derived immunity); one parameter reflecting the relative reduction in infectiousness of vaccinated individuals who get infected; and one parameter that reflects the relative reduction in reporting probability of vaccinated individuals due to a possible reduction in severity of symptoms. Only the first four parameters affect disease transmission (as measured by the basic reproduction number). The reduction in transmission due to vaccination is different for age-structured models than for homogeneous models. Notably, if the vaccine exhibits waning protection this could be larger for an age-structured model with high contact rates between young children who are still protected by the vaccine and lower contact rates between adults for whom protection might have already waned. Analytic expressions for age-specific "vaccine impacts" were also derived. The overall vaccine impact is bounded between the age-specific impact for the oldest age class and that of the youngest age class.

The economic impact of prenatal varicella immunity among pregnant women in Alberta

In light of the changing epidemiology of varicella, we sought to examine varicella antibody levels in the prenatal population in the Canadian province of Alberta. All prenatal varicella screening tests performed between August 1, 2002 and February 2, 2014 (454,592) were included in this study. Test results, demographics and vaccination status were examined to identify varicella seroprevalence and correlates for being seronegative. An overall seroprevalence for varicella of 95.8% was found across all pregnancy screenings. Significant independent correlates of seronegativity included younger age (AOR: 4.72 (95% CI: 3.87–5.77) for <20years of age vs. >40years of age) and having immigrated to Alberta from Africa or Asia (AOR: 4.55 (95% CI: 4.10–5.05) and AOR: 5.83 (95%CI; 5.48–6.19), respectively). Women who were initially seronegative for varicella antibodies and who received both postnatal vaccination and post-vaccination prenatal screening (2566) were examined to assess seroconversion. 66.3% of women who were tested up to six months post-vaccination were seropositive, however only 36.9% of women tested after 36months were seropositive. Finally, 40.9% of all prenatal varicella specimens tested were deemed redundant, i.e. women had either a history of (1) ⩾2 doses of varicella vaccine, (2) varicella infection, or (3) a previous positive varicella serology. Eliminating this redundant screening could provide an estimated $96,000 in savings annually in laboratory and Public Health follow-up costs alone. As the number of women with vaccine-derived immunity through universal childhood vaccination increase in the prenatal population, screening methods may need to adapt to ensure varicella immunity is accurately conducted and assessed.

Did Large-Scale Vaccination Drive Changes in the Circulating Rotavirus Population in Belgium?

Vaccination can place selective pressures on viral populations, leading to changes in the distribution of strains as viruses evolve to escape immunity from the vaccine. Vaccine-driven strain replacement is a major concern after nationwide rotavirus vaccine introductions. However, the distribution of the predominant rotavirus genotypes varies from year to year in the absence of vaccination, making it difficult to determine what changes can be attributed to the vaccines. To gain insight in the underlying dynamics driving changes in the rotavirus population, we fitted a hierarchy of mathematical models to national and local genotype-specific hospitalization data from Belgium, where large-scale vaccination was introduced in 2006. We estimated that natural- and vaccine-derived immunity was strongest against completely homotypic strains and weakest against fully heterotypic strains, with an intermediate immunity amongst partially heterotypic strains. The predominance of G2P[4] infections in Belgium after vaccine introduction can be explained by a combination of natural genotype fluctuations and weaker natural and vaccine-induced immunity against infection with strains heterotypic to the vaccine, in the absence of significant variation in strain-specific vaccine effectiveness against disease. However, the incidence of rotavirus gastroenteritis is predicted to remain low despite vaccine-driven changes in the distribution of genotypes.

Perfluoroalkyl and polyfluoroalkyl substances and indicators of immune function in children aged 12-19 y: National Health and Nutrition Examination Survey.

BackgroundPerfluoroalkyl and polyfluoroalkyl substances (PFAS) are immunotoxic in laboratory studies. Humans studies of immune effects are inconsistent. Using the U.S. National Health and Nutrition Examination Survey (NHANES) we examined PFAS serum concentration and indicators of prevalent immune function among 12 to 19 year old children.MethodsIn this cross-sectional study we examined PFAS serum concentration in relation to measles, mumps, and rubella antibody concentrations in NHANES 1999 – 2000 and 2003 – 2004 (n=1,191) and to allergic conditions and allergic sensitization in NHANES 2005 – 2006 (n=640).ResultsIn adjusted, survey-weighted models, a doubling of perfluorooctane sulfonate (PFOS) concentration among seropositive children was associated with a 13.3% (95% CI −19.9, −6.2) decrease in rubella antibody concentration and a 5.9% decrease in mumps antibody concentration (95% CI −9.9, −1.6). We observed no adverse association between exposure and current allergic conditions, including asthma. Children with higher PFOS concentration were less likely to be sensitized to any allergen (OR 0.74, 95% CI 0.58, 0.95).ConclusionIncreased exposure to several PFAS was associated with lower levels to mumps and rubella antibody concentrations, especially among seropositive individuals. These lower antibody concentrations may indicate a less robust response to vaccination or greater waning of vaccine-derived immunity over time.

Achieving a polio free world

Recently, the World Health Organization (WHO) declared that the spread of polio is an international public health emergency, and a coordinated international response is sought. Although the importance of such a response is recognized, there are challenges to stopping the spread of polio and achieving a polio free world. The most important issue is directing limited national resources to the specific areas where polio is endemic. In an article published in BMC Medicine, Upfill-Brown and his colleagues recognized this problem and successfully identified the potential risk areas in Nigeria using a validated spatial predictive model of wild poliovirus circulation. They also showed that a lower vaccine-derived population immunity is associated with the probability of a higher number of wild poliovirus cases within a district. Identification of the potential risk areas and understanding the magnitude of risk may help direct limited resources of the endemic countries to areas most at risk to maximize the impact of interventions and motivate the people to participate in the intervention program. These efforts are crucial if these endemic countries hope to eradicate polio.Please see related research article: http://www.biomedcentral.com/1741-7015/12/92.

Predictive spatial risk model of poliovirus to aid prioritization and hasten eradication in Nigeria.

BackgroundOne of the challenges facing the Global Polio Eradication Initiative is efficiently directing limited resources, such as specially trained personnel, community outreach activities, and satellite vaccinator tracking, to the most at-risk areas to maximize the impact of interventions. A validated predictive model of wild poliovirus circulation would greatly inform prioritization efforts by accurately forecasting areas at greatest risk, thus enabling the greatest effect of program interventions.MethodsUsing Nigerian acute flaccid paralysis surveillance data from 2004-2013, we developed a spatial hierarchical Poisson hurdle model fitted within a Bayesian framework to study historical polio caseload patterns and forecast future circulation of type 1 and 3 wild poliovirus within districts in Nigeria. A Bayesian temporal smoothing model was applied to address data sparsity underlying estimates of covariates at the district level.ResultsWe find that calculated vaccine-derived population immunity is significantly negatively associated with the probability and number of wild poliovirus case(s) within a district. Recent case information is significantly positively associated with probability of a case, but not the number of cases. We used lagged indicators and coefficients from the fitted models to forecast reported cases in the subsequent six-month periods. Over the past three years, the average predictive ability is 86 ± 2% and 85 ± 4% for wild poliovirus type 1 and 3, respectively. Interestingly, the predictive accuracy of historical transmission patterns alone is equivalent (86 ± 2% and 84 ± 4% for type 1 and 3, respectively). We calculate uncertainty in risk ranking to inform assessments of changes in rank between time periods.ConclusionsThe model developed in this study successfully predicts districts at risk for future wild poliovirus cases in Nigeria. The highest predicted district risk was 12.8 WPV1 cases in 2006, while the lowest district risk was 0.001 WPV1 cases in 2013. Model results have been used to direct the allocation of many different interventions, including political and religious advocacy visits. This modeling approach could be applied to other vaccine preventable diseases for use in other control and elimination programs.