Protection against omicron (B.1.1.529) BA.2 reinfection conferred by primary omicron BA.1 or pre-omicron SARS-CoV-2 infection among health-care workers with and without mRNA vaccination: a test-negative case-control study.

BACKGROUND: There is a paucity of data on vaccine-induced or infection-induced (hybrid or natural) immunity against omicron (B.1.1.529) subvariant BA.2, particularly in comparing the effects of previous SARS-CoV-2 infection with the same or different genetic lineage. We aimed to estimate the protection against omicron BA.2 associated with previous primary infection with omicron BA.1 or pre-omicron SARS-CoV-2, among health-care workers with and without mRNA vaccination. METHODS: We conducted a test-negative case-control study among health-care workers aged 18 years or older who were tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 was the predominant variant and was presumptively diagnosed with a positive test result. We identified cases (positive test during study period) and controls (negative test during study period) using the provincial laboratory database that records all nucleic acid amplification testing for SARS-CoV-2 in Quebec, and used the provincial immunisation registry to determine vaccination status. Logistic regression models compared the likelihood of BA.2 infection or reinfection (second positive test ≥30 days after primary infection) among health-care workers who had previous primary infection and none to three mRNA vaccine doses versus unvaccinated health-care workers with no primary infection. FINDINGS: 258 007 SARS-CoV-2 tests were done during the study period. Among those with a valid result and that met the inclusion criteria, there were 37 732 presumed BA.2 cases (2521 [6·7%] reinfections following pre-omicron primary infection and 659 [1·7%] reinfections following BA.1 primary infection) and 73 507 controls (7360 [10·0%] had pre-omicron primary infection and 12 315 [16·8%] had BA.1 primary infection). Pre-omicron primary infection was associated with a 38% (95% CI 19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those who had also received one (56%, 95% CI 47-63), two (69%, 64-73), or three (70%, 66-74) mRNA vaccine doses. Omicron BA.1 primary infection was associated with greater protection against BA.2 infection (risk reduction of 72%, 95% CI 65-78), and protection was increased further among those who had received two doses of mRNA vaccine (96%, 95-96), but was not improved with a third dose (96%, 95-97). INTERPRETATION: Health-care workers who had received two doses of mRNA vaccine and had previous BA.1 infection were subsequently well protected for a prolonged period against BA.2 reinfection, with a third vaccine dose conferring no improvement to that hybrid protection. If this protection also pertains to future variants, there might be limited benefit from additional vaccine doses for people with hybrid immunity, depending on timing and variant. FUNDING: Ministère de la Santé et des Services Sociaux du Québec.

Clinicians Are Not Able to Infer Parental Intentions to Vaccinate Infants with a Seasonal Influenza Vaccine, and Perhaps They Should Not Try: Findings from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)-IV.

This prospective cohort survey evaluated the concordance of clinicians' perceptions of parental intentions and parents' actual intentions to vaccinate their infants against influenza. During a routine healthy baby visit, clinicians provided parents with information about influenza, children's vulnerability to influenza, and nonadjuvanted and adjuvanted trivalent influenza vaccines (TIV and aTIV, respectively). Before and after the clinician−parent interaction, parents were surveyed about their attitudes, their perceptions of support from significant others, and the intention to vaccinate their infant with aTIV. Clinicians were asked about their perception of parents' intentions to choose aTIV for their children. These assessments included 24 clinicians at 15 community practices and nine public health clinics, and 207 parents. The correlation coefficients of the clinicians' assessment of parents' intention to vaccinate were 0.483 (p < 0.001) if the vaccine was presented as free of cost, 0.266 (p < 0.001) if the cost was $25, and 0.146 (p = 0.036) if the cost was $50, accounting for 23%, 7%, and 2% of the variance in parental intentions, respectively. The clinicians were poor at predicting parental intentions to immunize, particularly when cost was involved. Information on vaccine options and influenza infection should be provided for every eligible patient to allow parents to determine if the vaccine is appropriate for their child.

Parental Attitudes and Perceptions of Support after Brief Clinician Intervention Predict Intentions to Accept the Adjuvanted Seasonal Influenza Vaccination: Findings from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)-I.

Adjuvanted trivalent influenza vaccine (aTIV) provides enhanced protection against seasonal influenza in children compared with nonadjuvanted trivalent influenza vaccine (TIV). This prospective cohort study assessed parental attitudes, beliefs, and intentions to vaccinate their infants aged 6-23 months with aTIV. Parents were surveyed before and after routine healthy baby visits, and post clinician interaction results were analyzed using multivariable logistic regression. Physicians at 15 community practice clinics and nurses at 3 public health clinics participated; 207 parents were surveyed. After clinician consultation, most parents considered immunization with aTIV to be safe (72.9%), effective (69.6%), and important (69.0%); most perceived support for vaccination from significant others (62.8%) and clinicians (81.6%); and 66.6% intended to vaccinate their infant with aTIV. Parental attitudes toward vaccinating their infant with aTIV were strongly correlated with perceptions of vaccine safety, efficacy, and importance, and these represented the strongest influence on intentions to vaccinate (odds ratio (OR) 79.25; 95% confidence interval (CI) 6.05-1037.50). Parental intentions were further influenced by perceived strength of clinician recommendation (OR 4.55, 95% CI 1.38-15.06) and social support for vaccination (OR 3.46, 95% CI 0.50-24.13). These findings may inform clinician approaches to parental education to ensure optimal seasonal pediatric influenza vaccination.

The impact of influenza on the ability to work, volunteer and provide care: results from an online survey of Canadian adults 50 years and older.

BACKGROUND: Influenza is associated with a decline in functional abilities among Canadian older adults, although specific impacts on daily life have not been fully explored. METHODS: In August 2019 and May 2020, we conducted surveys of Canadian adults 50-64 years and 65 years and older through an online market research platform. The survey included questions about the impact of diagnosed influenza or self-reported influenza-like-illness (ILI) on working, volunteering and caregiving. RESULTS: We surveyed 1006 adults in the 50-64 year age group about the 2018/19 season and 1001 about the 2019/20 season. In the 65 years and older age group, we surveyed 3548 and 3500 individuals about the 2018/19 and 2019/20 influenza seasons, respectively. In each season, nearly two-thirds of individuals 50-64 years with influenza/ILI were employed; 51.7% reported absenteeism in 2018/19 and 53.6% in 2019/20. Of the 20% of individuals 65 years and older who were employed, 47.0% of those with influenza/ILI were absent while ill in 2018/19 (39.8% in 2019/20). In 2018/2019, 29.6% of respondents 50-64 years old with influenza/ILI identified as volunteers (29.3% in 2019/2020). In both seasons, nearly half were unable to do so while ill. Of the 164 (32.7%) individuals 65 years and older who volunteered during the 2018/19 season, 80 (48.8%) did not while ill; 224 (37.3%) respondents volunteered in the 2019/20 season, and half were absent while ill. Of those 50-64 years with influenza/ILI, 97 (42.2%) and 57 (22.2%) were caregivers in 2018/19 and 2019/20, respectively. In 2018/19 and 2019/20, 40 (41.2%) and 28 (49.1%) caregivers were unable to provide care when ill, respectively. Of those with influenza/ILI in the 65 years and older age group, 123 (24.6%) and 162 (27.0%) were caregivers in 2018/19 and 2019/20, respectively. In 2018/19, 18 (14.6%) caregivers with influenza/ILI did not provide care while ill (42 [25.9%] in 2019/20). DISCUSSION: In Canadian older adults, influenza and ILI had notable impacts on ability to volunteer and provide care across two recent seasons. Optimization of influenza prevention in this population may yield important societal benefits.

Estimated Protection of Prior SARS-CoV-2 Infection Against Reinfection With the Omicron Variant Among Messenger RNA-Vaccinated and Nonvaccinated Individuals in Quebec, Canada.

Importance: The Omicron variant is phylogenetically and antigenically distinct from earlier SARS-CoV-2 variants and the original vaccine strain. Protection conferred by prior SARS-CoV-2 infection against Omicron reinfection, with and without vaccination, requires quantification. Objective: To estimate the protection against Omicron reinfection and hospitalization conferred by prior heterologous non-Omicron SARS-CoV-2 infection and/or up to 3 doses of an ancestral, Wuhan-like messenger RNA (mRNA) vaccine. Design, Setting, and Participants: This test-negative, population-based case-control study was conducted between December 26, 2021, and March 12, 2022, and included community-dwelling individuals aged 12 years or older who were tested for SARS-CoV-2 infection in the province of Quebec, Canada. Exposures: Prior laboratory-confirmed SARS-CoV-2 infection with or without mRNA vaccination. Main Outcomes and Measures: The main outcome was laboratory-confirmed SARS-CoV-2 reinfection and associated hospitalization, presumed to be associated with the Omicron variant according to genomic surveillance. The odds of prior infection with or without vaccination were compared for case participants with Omicron infection and associated hospitalizations vs test-negative control participants. Estimated protection was derived as 1 - the odds ratio, adjusted for age, sex, testing indication, and epidemiologic week. Analyses were stratified by severity and time since last non-Omicron infection or vaccine dose. Results: This study included 696 439 individuals (224 007 case participants and 472 432 control participants); 62.2% and 63.9% were female and 87.4% and 75.5% were aged 18 to 69 years, respectively. Prior non-Omicron SARS-CoV-2 infection was detected for 9505 case participants (4.2%) and 29 712 control participants (6.3%). Among nonvaccinated individuals, prior non-Omicron infection was associated with a 44% reduction (95% CI, 38%-48%) in Omicron reinfection risk, which decreased from 66% (95% CI, 57%-73%) at 3 to 5 months to 35% (95% CI, 21%-47%) at 9 to 11 months postinfection and was below 30% thereafter. The more severe the prior infection, the greater the risk reduction. Estimated protection (95% CI) against Omicron infection was consistently significantly higher among vaccinated individuals with prior infection compared with vaccinated infection-naive individuals, with 65% (63%-67%) vs 20% (16%-24%) for 1 dose, 68% (67%-70%) vs 42% (41%-44%) for 2 doses, and 83% (81%-84%) vs 73% (72%-73%) for 3 doses. For individuals with prior infection, estimated protection (95% CI) against Omicron-associated hospitalization was 81% (66%-89%) and increased to 86% (77%-99%) with 1, 94% (91%-96%) with 2, and 97% (94%-99%) with 3 mRNA vaccine doses, without signs of waning. Conclusions and Relevance: The findings of this study suggest that vaccination with 2 or 3 mRNA vaccine doses among individuals with prior heterologous SARS-CoV-2 infection provided the greatest protection against Omicron-associated hospitalization. In the context of program goals to prevent severe outcomes and preserve health care system capacity, a third mRNA vaccine dose may add limited protection in twice-vaccinated individuals with prior SARS-CoV-2 infection.

Understanding the Impact of Approved but Unfunded Vaccine Status on Parental Acceptance of an Adjuvanted Seasonal Influenza Vaccine for Infants: Results from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)-III.

The adjuvanted trivalent influenza vaccine (aTIV) provides enhanced protection against influenza for infants but is not publicly funded (NPF). The objective of this prospective cohort study of parents with children 6 through 23 months of age was to understand how NPF status influences parental perceptions of approved but unfunded vaccines and their intentions to vaccinate. At healthy baby visits, clinicians provided parents with information about influenza and vaccination. Before and after these interactions, a research nurse assessed parents' intentions to vaccinate their children and their beliefs about the safety, efficacy, and necessity of vaccinating their children with aTIV in both publicly funded (PF) and NPF settings. Overall, 15 community practice clinics (n = 15 physicians) and nine public health clinics (n = 9 nurses) recruited 207 parents. The percentage of parents intending to immunize their children with aTIV decreased from 72% (vaccine PF, free of charge), to 42% (NPF, $25 per dose), to 27% (NPF, $50 per dose). Funding status strongly influenced whether parents perceived immunization with aTIV to be necessary, safe, and effective. Information on influenza and influenza vaccines should be provided to parents routinely to allow for well-informed decisions on the suitability of specific influenza vaccines for their child.

Symptomatology during previous SARS-CoV-2 infection and serostatus before vaccination influence the immunogenicity of BNT162b2 COVID-19 mRNA vaccine.

Public health vaccination recommendations for COVID-19 primary series and boosters in previously infected individuals differ worldwide. As infection with SARS-CoV-2 is often asymptomatic, it remains to be determined if vaccine immunogenicity is comparable in all previously infected subjects. This study presents detailed immunological evidence to clarify the requirements for one- or two-dose primary vaccination series for naturally primed individuals. The main objective was to evaluate the immune response to COVID-19 mRNA vaccination to establish the most appropriate vaccination regimen to induce robust immune responses in individuals with prior SARS-CoV-2 infection. The main outcome measure was a functional immunity score (zero to three) before and after vaccination, based on anti-RBD IgG levels, serum capacity to neutralize live virus and IFN-γ secretion capacity in response to SARS-CoV-2 peptide pools. One point was attributed for each of these three functional assays with response above the positivity threshold. The immunity score was compared based on subjects' symptoms at diagnosis and/or serostatus prior to vaccination. None of the naïve participants (n=14) showed a maximal immunity score of three following one dose of vaccine compared to 84% of the previously infected participants (n=55). All recovered individuals who did not have an immunity score of three were seronegative prior to vaccination, and 67% had not reported symptoms resulting from their initial infection. Following one dose of vaccine, their immune responses were comparable to naïve individuals, with significantly weaker responses than individuals who were symptomatic during infection. These results indicate that the absence of symptoms during initial infection and negative serostatus prior to vaccination predict the strength of immune responses to COVID-19 mRNA vaccine. Altogether, these findings highlight the importance of administering the complete two-dose primary regimen and following boosters of mRNA vaccines to individuals who experienced asymptomatic SARS-CoV-2 infection.

The REinfection in COVID-19 Estimation of Risk (RECOVER) study: Reinfection and serology dynamics in a cohort of Canadian healthcare workers.

BACKGROUND: Understanding the immune response to natural infection by SARS-CoV-2 is key to pandemic management, especially in the current context of emerging variants. Uncertainty remains regarding the efficacy and duration of natural immunity against reinfection. METHODS: We conducted an observational prospective cohort study in Canadian healthcare workers (HCWs) with a history of PCR-confirmed SARS-CoV-2 infection to (i) measure the average incidence rate of reinfection and (ii) describe the serological immune response to the primary infection. RESULTS: Our cohort comprised 569 HCWs; median duration of individual follow-up was 371 days. We detected six cases of reinfection in absence of vaccination between August 21, 2020, and March 1, 2022, for a reinfection incidence rate of 4.0 per 100 person-years. Median duration of seropositivity was 415 days in symptomatics at primary infection compared with 213 days in asymptomatics (p < 0.0001). Other characteristics associated with prolonged seropositivity for IgG against the spike protein included age over 55 years, obesity, and non-Caucasian ethnicity. CONCLUSIONS: Among unvaccinated healthcare workers, reinfection with SARS-CoV-2 following a primary infection remained rare.

Continuing Medical Education Improves Physician Communication Skills and Increases Likelihood of Pediatric Vaccination: Findings from the Pediatric Influenza Vaccination Optimization Trial (PIVOT)-II.

This study evaluated the impact of a continuing medical education (CME) program that emphasized actionable information, motivation to act, and skills to strengthen physician recommendations for seasonal influenza vaccination in children 6 through 23 months of age for whom influenza immunization rates are suboptimal. Physicians were randomly assigned to an accredited CME program or to no CME. Participants completed pre- and post-study questionnaires. Influenza immunization rates were compared between groups. A total of 33 physicians in the CME group and 35 in the control group documented 292 and 322 healthy baby visits, respectively. Significantly more parents immunized their children against influenza after interacting with CME-trained physicians than those with no CME training (52.9% vs. 40.7%; p = 0.007). The odds ratio for vaccination after visits with CME-trained physicians was 1.52 (95% confidence interval 1.09 to 2.12; p = 0.014), which was unaffected by the socioeconomic status of parents. Parents who discussed influenza vaccination with CME-trained physicians were 20% more likely to choose an approved but publicly unfunded adjuvanted pediatric influenza vaccine. The percentages of physicians reporting the highest levels of knowledge, ability, and confidence doubled or tripled after the CME intervention. Significantly more parents immunized very young children after interacting with physicians who had undergone CME training.

Sexual behavior, clinical outcomes and attendance of cervical cancer screening by HPV vaccinated and unvaccinated sexually active women.

Concerns were raised about HPV vaccination possibly leading to riskier sexual behavior. We assessed sexual behaviors, risk of sexually transmitted infection, and attendance to cervical cancer screening by HPV vaccinated and unvaccinated young women. In this analysis, 1475 questionnaires completed by women aged 17-29 years were included. The majority of respondents (67.9%) were vaccinated against HPV. The proportion of those vaccinated decreased with age: from 93.2% in those aged 17-19 to 72.9% in those aged 20-22, and 21.8% in 23-29-year olds. A higher proportion of unvaccinated respondents had at least one sexual intercourse under the age of 15 when compared to those vaccinated (30% vs. 23%, p < .0001). The number of sexual partners during the last 12 months was similar between vaccinated and unvaccinated participants. Vaccinated participants reported more condom use (45% versus 38%; p = .0002), and less sexually transmitted infections (10% versus 28%; p < .0001), and less anogenital condylomas (2.2% vs. 11.6%; p < .0001). A screening test has been reported by 51% and 77% of vaccinated and unvaccinated participants, respectively (p < .0001). The association between vaccination status and cervical cancer screening disappeared when adjusting for participants' age. The study results consolidate the existing body of data regarding the absence of an impact of HPV vaccination on sexual behavior or use of contraceptives.

COVID-19's Impact on Willingness to Be Vaccinated against Influenza and COVID-19 during the 2020/2021 Season: Results from an Online Survey of Canadian Adults 50 Years and Older.

There is considerable overlap in age-related risk factors for influenza and COVID-19. We explored the impact of the pandemic on anticipated influenza and COVID-19 vaccination behaviour in the 2020/2021 season. In May 2020, we conducted online surveys of Canadian adults 50 years and older via a market research panel platform, as part of a series of annual surveys to understand experiences with influenza. Given the current pandemic, respondents were also asked about COVID-19's impact on their vaccination decision-making for the 2020/2021 season. Of 1001 respondents aged 50-64 years, 470 (47.0%) originally intended on receiving the influenza vaccine and still planned to do so, while 200 (20%) respondents who had planned to abstain now reported willingness to receive the vaccine due to COVID-19. In the 65+ age group, 2525 (72.1%) reported that they had planned to be vaccinated and that COVID-19 had not changed their mind, while 285 individuals (8.1%) reported that they had initially planned to forgo the vaccine but now intended to receive it. Reasons for this change included COVID-19's demonstration of the devastating potential of viruses; and to protect against influenza, and decrease vulnerability to COVID-19. If the COVID-19 vaccine was available, 69.1% of 50-64 year olds and 79.5% of those 65 years and older reported they would opt to receive it. The COVID-19 pandemic has been a sobering demonstration of the dangers of infectious disease, and the value of vaccines, with implications for influenza and COVID-19 immunization programs.

A systematic literature review of the recombinant subunit herpes zoster vaccine use in immunocompromised 18-49 year old patients.

BACKGROUND: The adjuvanted recombinant zoster vaccine (RZV) is indicated for prevention of herpes zoster (HZ) in adults aged ≥50 years. Questions regarding the use of RZV in immunocompromised patients < 50-year-old, who are at increased risk for HZ, were raised. OBJECTIVES: The objective of this systematic review was to consolidate existing evidences on safety, immunogenicity and efficacy of RZV in immunocompromised adults aged 18-49 years. METHODS: Four databases were searched. Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) guidelines were followed. Screening and classification of search items was performed using the web-based platform DistillerSR. RESULTS: The search identified 1389 potentially relevant records. Six studies fulfilled inclusion criteria. The proportion of patients aged 18-49 varied between 23 and 62%. Pain at injection site (98.6%) and fatigue (75.3%) were the most common adverse events. The proportion of patients reporting serious adverse events (SAEs) ranged between 8.1 and 30.8% in RZV and between 4.1 and 36.5% in placebo groups. SAEs deemed related to vaccination were reported in < 1% of patients in both RZV and placebo groups. The proportion of patients that experienced clinically significant underlying disease-related events ranged between 0.0 and 20.0% in RZV and 0.0 and 26.7% in placebo groups. The humoral and cell-mediated immune response rate ranged between 65.4 and 96.2% and 50.0-93.0%, respectively. Vaccine efficacy in hematopoietic stem cell transplant patients was 72% (95%CI, 39-88%) in 18-49-year-olds and 67% (95%CI, 53-78%) in ≥ 50-year-olds (median follow-up 21 months). Vaccine efficacy in ≥ 18-year-old patients with hematologic malignancies was estimated at 87.2% (95%CI, 44.3-98.6%) up to 13 months post-vaccination. CONCLUSIONS: Results suggest that RZV has an acceptable safety profile and induces immunity in an important proportion of ≥ 18-year-old immunocompromised patients. Longer follow-up studies are warranted to assess the duration of RZV induced immunity in immunocompromised patients.

Priming effect of bivalent and quadrivalent vaccine for HPV 31/33/45/52: an exploratory analysis from two clinical trials.

The main objective of this post hoc analysis is to compare the magnitude of the immune response to HPV31/33/45/52 and 58 after a dose of 9vHPV vaccine given to naïve (previously unvaccinated) subjects and subjects previously vaccinated with a dose of 2vHPV or 4vHPV vaccine. Results from two clinical trials conducted in the same region, in comparable populations and by the same research team were included in this analysis. In study A, a dose of 9vHPV was administered 6 months after a single dose of 2vHPV as well as to naïve subjects. In study B, a dose of 9vHPV was administered 36-96 months (mean 65 months) after a single dose of 4vHPV. Blood samples were collected just before and one month post-9vHPV vaccine administration. For both studies, antibody responses were measured using the same 9-plex virus-like particle based IgG ELISA (M9ELISA). One month after 9vHPV dose administration, all subjects were seropositive to HPV 31/33/45/52 and 58. Subjects who had previously received 2vHPV or 4vHPV had significantly higher (1.8-8.0-fold) GMTs than naive subjects for HPV31/33/45/52 types but not for HPV58. GMTs to HPV31/33/45/52 and 58 were not significantly different between subjects who received a 2vHPV or 4vHPV dose prior to 9vHPV. The strong anamnestic response to one dose of 9vHPV given as late as 3-8 years after a single dose of 2vHPV or 4vHPV vaccine indicates these vaccines induced priming to types only included in the 9vHPV vaccine.

Immunogenicity of 2 and 3 Doses of the Quadrivalent Human Papillomavirus Vaccine up to 120 Months Postvaccination: Follow-up of a Randomized Clinical Trial.

BACKGROUND: Several countries have implemented a 2-dose (2D) human papillomavirus (HPV) vaccination schedule for adolescents based on immunobridging studies. We compared immunogenicity of 2D vs 3-dose (3D) schedules of the quadrivalent vaccine (4vHPV) up to 10 years after the first dose. METHODS: Girls aged 9-13 years were randomized to receive 2D or 3D and were compared with women aged 16-26 receiving 3D at day 1 and months 7, 24, and 120 after the first dose. Antibody levels for HPV6/11/16/18 were evaluated using the competitive Luminex immunoassay (cLIA) and total immunoglobulin G assay. Geometric mean titers (GMTs) and seropositivity rates were compared between the different groups at different time points. Noninferiority of GMT ratios was defined as the lower bound of the 2-sided 95% confidence interval (CI) being greater than 0.5. Kinetics of antibody titers over time among study groups were examined. RESULTS: At 120 months, data from 35 2D girls, 38 3D girls, and 30 3D women were used for analyses. cLIA seropositivity rates were above 95% for all HPV vaccine types and all schedules, except HPV18, with the lowest seropositivity observed among 3D women (60.0%; 95% CI, 40.6%-77.3%). GMT ratios (cLIA) for both 2D and 3D girls were noninferior to 3 doses in women for HPV6/11/16/18. Trends were comparable between assays. CONCLUSIONS: GMTs for HPV6/11/16/18 after 2D or 3D of 4vHPV in girls were noninferior to 3D in adult women up to 120 months postvaccination. This study demonstrates long-term immunogenicity of the 2D HPV vaccine schedule.

The immune response to a two-dose schedule of quadrivalent HPV vaccine in 9-13 year-old girls: Is it influenced by age, menarche status or body mass index?

HPV vaccines are highly immunogenic. A two-dose schedule for 9-14 year-old is recommended. However, no data exist regarding the impact of age, menarche status and body mass index (BMI) on the immune response to a two-dose schedule. In this post-hoc analysis, we present antibody titers to HPV6/11/16/18 in 9-13 year-old girls participating in a randomized clinical trial and assigned to receive two doses of quadrivalent HPV vaccine at 6 months interval (NCT00501137). Antibody titers were measured at month 7 and 24 of the study by using a competitive Luminex immunoassay (cLIA).Both, at Month 7 and 24 the GMTs for four HPV genotypes were similar across the age bands, and did not vary significantly by menarche status. Overweight and obese girls had lower GMTs. More than 99% of girls remained seropositive for HPV 6/11/16 and 89% for HPV18 at month 24. Comprehensive data in overweight and obese vaccines are warranted.

Effectiveness and cost-effectiveness of vaccination against herpes zoster in Canada: a modelling study.

BACKGROUND: Two vaccines against herpes zoster are currently authorized for use in Canada: the recombinant subunit zoster vaccine and live attenuated zoster vaccine. We compared the effectiveness and cost-effectiveness of these 2 vaccines. METHODS: We used a decision analytic static cohort model parametrized with Canadian epidemiologic and economic data. We performed the economic analysis from the health care system perspective, using a lifetime horizon and a 3% discount rate for costs and benefits. The primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained, relative to no vaccination. We ran 30 000 simulations varying all model parameters, including vaccine costs, efficacy and waning. RESULTS: The number needed to vaccinate (NNV) was higher for the live attenuated zoster vaccine than for the recombinant subunit zoster vaccine for all herpes zoster-related events at all ages. For example, in persons exactly 65 years old, for herpes zoster, median NNV was 21 (90% uncertainty interval [UI] 13-31) versus 8 (90% UI 6-18), and for postherpetic neuralgia, NNV was 64 (90% UI 33-93) versus 31 (90% UI 23-73). For the recombinant vaccine, the median cost-effectiveness ratios varied between cost-saving and $25 881 per QALY gained for adults aged 50 years or older. For the live vaccine, the cost-effectiveness ratios varied between cost-saving and $130 587 per QALY gained and were less than $45 000 per QALY gained only for those 65 to 75 years old. Given its higher efficacy, we estimated that the cost for the complete series of the recombinant vaccine could be $150 to $200 more than the cost of the live vaccine and still be considered cost-effective. INTERPRETATION: Our model predicted that the recombinant subunit zoster vaccine is likely cost-effective in Canada for adults 60 years or older, and is likely more cost-effective than live attenuated zoster vaccine. These results have informed updated national and provincial recommendations on herpes zoster vaccination.

EXamining the knowledge, Attitudes and experiences of Canadian seniors Towards influenza (the EXACT survey).

BACKGROUND: Older adults are at high risk for influenza-related complications including worsening frailty and function. We surveyed older Canadians to explore the impact of influenza and determine how influenza knowledge influences vaccination decision-making. METHODS: We disseminated an online survey through a national polling panel. The survey included questions about the respondents' influenza vaccination practices and knowledge about influenza. Using validated measures, they reported their frailty and functional status prior to the 2016/17 influenza season, during illness (if applicable), and following the season. Regression analyses were used to examine predictors of poor functional outcomes. RESULTS: Five thousand and fourteen adults aged 65 and older completed the survey; mean age was 71.3 ± 5.17 years, 42.6% had one or more chronic conditions, 7.8% were vulnerable and 1.8% were frail. 67.9% reported receiving last season's influenza vaccine. Those who rarely/never receive the influenza vaccine were significantly less likely to correctly answer questions about influenza's impact than those who receive the vaccine more consistently. Of the 1035 (21.5%) who reported experiencing influenza or influenza-like illness last season, 40% indicated a recovery longer than 2 weeks, and one-fifth had health and function declines during this time. Additionally, 3.1% of those afflicted "never fully recovered". Older age, significant trouble with memory and having influenza/ILI were among the independent predictors of persistent declines in health and function. CONCLUSIONS: Given that frailty and function are important considerations for older adults' well-being and independence, healthcare decision-makers must understand the potential for significant temporary and long-term impacts of influenza to make informed vaccine-related policies and recommendations.

Long intervals between two doses of HPV vaccines and magnitude of the immune response: a post hoc analysis of two clinical trials.

The objective of this analysis was to compare the anti-HPV GMTs and their distribution after a 6-month or a 3-8 -y interval between two HPV vaccine doses. The results from two clinical trials, conducted by the same team in the same region, with serological assays performed at the same laboratory using the same ELISA methodology were compared. In the first study, 173 9-10-y-old girls and boys received two doses of 9vHPV vaccine at a 6-month interval; in the second study, 31 girls vaccinated with one dose of 4vHPV at the age of 9-14 y received a dose of 9vHPV 3-8 y later (mean 5.4 y). In both studies, blood samples were collected before and 1 month post second dose. Despite large differences in the time since the first dose, all subjects (100%) were seropositive to the common 4 HPV types (6, 11, 16 and 18) to both vaccines, with comparable GMTs and titer distributions before the second dose. One month post second dose, the GMTs increased 40-91-fold for those with a 6-month interval between doses and 60-82-fold for those with a 3-8-y interval. Titer distributions after the booster dose were comparable in the two studies. These results indicate that 2-dose HPV vaccination schedules with an interval of several years could be used for pre-adolescents. Intervals longer than 6 months may facilitate logistics for immunization programs and could be useful during periods of vaccine shortage or as a transition while the effectiveness of a one-dose schedule is being evaluated.

Canadian older adults' perceptions of effectiveness and value of regular and high-dose influenza vaccines.

Influenza vaccination is an important public health intervention for older adults, yet vaccination rates remain suboptimal. We conducted an online survey of Canadians ≥ 65 years to explore satisfaction with publicly-funded standard-dose influenza vaccines, and perceptions of the need for a more effective product. They were provided with information about currently approved influenza vaccines, and were asked about their preferences should all formulations be available for free, and should the recently approved high-dose (HD) vaccine for seniors be available at a cost. From March to April 2017, 5014 seniors completed the survey; mean age was 71.3 ± 5.17 years, 50% were female, and 42.6% had one or more chronic conditions. 3403 (67.9%) had been vaccinated against influenza in the 2016/17 season. Of all respondents, 3460 (69%) were satisfied with the standard-dose influenza vaccines, yet 3067 (61.1%) thought that a more effective vaccine was/may be needed. If HD was only available at a cost, 1426 (28.4%) respondents would consider it, of whom 62.9% would pay $20 or less. If all vaccines were free next season, 1914 (38.2%) would opt for HD (including 12.2% of those who previously rejected influenza vaccines), 856 (17.1%) would choose adjuvanted vaccine, and 558 (11.1%) standard-dose vaccine. 843 (16.8%) of respondents were against vaccines, 451 (9.0%) had no preference and 392 (7.8%) were uncertain. Making this product available through publicly funded programs may be a strategy to increase immunization rates in this population.