Measles, mumps, and rubella (MMR) are among the most important viral infectious diseases in Iran and neighboring countries. After using a trivalent vaccine for these three diseases for a long time, in recent years, these diseases have been significantly controlled in Iran. One of the important points of storing the vaccine is that the vaccine strains are highly temperature-sensitive viruses. Due to tropical climatic conditions in Iran, the cold chain may not be achievable during the storage and transmission of the MMR vaccine. Therefore, the efficacy of the vaccine may be affected. This study aimed to evaluate the MMR vaccine potency at different temperatures (stress tests) and frequent light exposures. All quality control tests in the form of stability studies were performed on the samples from three consecutive batches produced during a full-scale Razi production. The samples were stored at 2-8, 22-25, 35-37, and 42-45°C in specific time intervals, exposed to frequent light, and underwent freezing/thawing conditions. According to the results, the storage of the vaccine at high temperatures caused a decrease in potency and increased moisture content in the vaccine vials. The best temperature for maintenance and transportation of MMR is 2-8°C. The time and frequency of light exposure may affect the vaccine potency. Based on the sensitivity of the vaccine strains to environmental conditions, the development of plans for storage and transportation of vaccines in different situations and training the vaccine injection staff seem necessary.

OBJECTIVE: To evaluate the dose-effect association between COVID-19 vaccination and probability of turning RT-PCR positive and to assess the correlation between disease severity and vaccination status.
METHODS: A single centre cross-sectional study was conducted amongst 583 individuals presenting to COVID-19 testing clinic and 55 hospitalized COVID-19 patients. Vaccination status was assessed by the number of doses and duration since the last dose. Disease severity was evaluated by the requirement of hospitalisation and ICU admission/death. The association between the vaccination status and development of disease and its severity were statistically analyzed.
RESULTS: The mean age of the population was 36.6 years and 82.6% had no comorbidities. The odds of turning RT-PCR positive was 0.17(95% CI: 0.11-0.27) among the clinical suspects who had taken both doses of the vaccine at least 14 days before (fully vaccinated). The odds of hospitalisation was 0.12(95% CI: 0.03-0.45) and ICU admission/death was 0.07(95% CI: 0.01-0.36) among fully vaccinated individuals. The protective role of vaccination was observed to start 14 days after receiving the first dose.
CONCLUSIONS: COVID-19 vaccination provides dose-dependent protection against the development of the disease. It also lowers the risk of hospitalisation and ICU admission/death in RT-PCR positive patients in a dose-dependent manner.

Shigella is the second most deadly diarrheal disease among children under five years of age, after rotavirus, with high morbidity and mortality in developing countries. Currently, no vaccine is widely available, and the increasing levels of multidrug resistance make Shigella a high priority for vaccine development. The single-component candidate vaccine against Shigella sonnei (1790GAHB), developed using the GMMA technology, contains the O antigen (OAg) portion of lipopolysaccharide (LPS) as active moiety. The vaccine was well tolerated and immunogenic in early-phase clinical trials. In a phase 1 placebo-controlled dose escalation trial in France (NCT02017899), three doses of five different vaccine formulations (0.06/1, 0.3/5, 1.5/25, 3/50, 6/100 µg of OAg/protein) were administered to healthy adults. In the phase 1 extension trial (NCT03089879), conducted 2-3 years following the parent study, primed individuals who had undetectable antibody levels before the primary series received a 1790GAHB booster dose (1.5/25 µg OAg/protein). Controls were unprimed participants immunized with one 1790GAHB dose. The current analysis assessed the functionality of sera collected from both studies using a high-throughput luminescence-based serum bactericidal activity (SBA) assay optimized for testing human sera. Antibodies with complement-mediated bactericidal activity were detected in vaccinees but not in placebo recipients. SBA titers increased with OAg dose, with a persistent response up to six months after the primary vaccination with at least 1.5/25 µg of OAg/protein. The booster dose induced a strong increase of SBA titers in most primed participants. Correlation between SBA titers and anti-S. sonnei LPS serum immunoglobulin G levels was observed. Results suggest that GMMA is a promising OAg delivery system for the generation of functional antibody responses and persistent immunological memory.

BACKGROUND: The effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in preventing pneumococcal pneumonia has been controversial.
METHODS: To evaluate the effectiveness of the PPSV23 in elderly outpatients with chronic respiratory diseases, we carried out a case-control study, including 4128 outpatients aged ≥ 65 years, in the respiratory department.
RESULTS: There were 320 vaccinated patients, of which 164 were diagnosed with pneumococcal pneumonia. The adjusted odds ratio was 0.39 (95% confidence interval (CI), 0.17 to 0.89). In the subsets consisting of age groups ≥ 70 and ≥ 75 years, the adjusted odds ratio (95% CI) was respectively 0.16 (0.04 to 0.67) and 0.15 (0.02 to 1.12).
CONCLUSIONS: This real-world study suggests that PPSV23 can be useful in preventing pneumococcal pneumonia in the elderly with chronic respiratory diseases.

Freeze-drying is a dehydration process that provides improved stability of vaccine formulations for shipment and storage. During the primary drying steps of the process, product temperature has to be maintained below a critical value to avoid visual defects of the product, leading to an increase of the sublimation time and thus of the operational costs. In this work, we used the design space approach together with experimental analysis for the development of the primary drying step of a vaccine model formulation. First, the formulation was characterized by determining the glass transition and the collapse temperatures. Successively, the dynamic design space of primary drying was calculated via mathematical modelling, and a proven acceptable range (PAR) was defined around the selected operating values. Finally, the cycle and the PAR were validated by performing a freeze-drying cycle at pilot scale and by evaluating the values of the product critical quality attributes (e.g. moisture content, visual aspect, reconstitution time).

Antibodies (Abs) specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (C1/C2) were induced in the RV144 vaccine trial, where antibody-dependent cellular cytotoxicity (ADCC) correlated with reduced risk of HIV-1 infection. We combined X-ray crystallography and fluorescence resonance energy transfer-fluorescence correlation spectroscopy to describe the molecular basis for epitopes of seven RV144 Abs and compared them to A32 and C11, C1/C2 Abs induced in HIV infection. Our data indicate that most vaccine Abs recognize the 7-stranded β-sandwich of gp120, a unique hybrid epitope bridging A32 and C11 binding sites. Although primarily directed at the 7-stranded β-sandwich, some accommodate the gp120 N terminus in C11-bound 8-stranded conformation and therefore recognize a broader range of CD4-triggered Env conformations. Our data also suggest that Abs of RV144 and RV305, the RV144 follow-up study, although likely initially induced by the ALVAC-HIV prime encoding full-length gp120, matured through boosting with truncated AIDSVAX gp120 variants.IMPORTANCE Antibody-dependent cellular cytotoxicity (ADCC) correlated with a reduced risk of infection from HIV-1 in the RV144 vaccine trial, the only HIV-1 vaccine trial to date to show any efficacy. Antibodies specific for CD4-induced envelope (Env) epitopes within constant region 1 and 2 (cluster A region) were induced in the RV144 trial and their ADCC activities were implicated in the vaccine efficacy. We present structural analyses of the antigen epitope targets of several RV144 antibodies specific for this region and C11, an antibody induced in natural infection, to show what the differences are in epitope specificities, mechanism of antigen recognition, and ADCC activities of antibodies induced by vaccination and during the course of HIV infection. Our data suggest that the truncated AIDSVAX gp120 variants used in the boost of the RV144 regimen may have shaped the vaccine response to this region, which could also have contributed to vaccine efficacy.

Influenza vaccination is recommended for all US residents aged ≥6 months. Vaccine effectiveness (VE) varies by age, circulating influenza strains, and the presence of high-risk medical conditions. We examined site-specific VE in the US Influenza VE Network, which evaluates annual influenza VE at ambulatory clinics in geographically diverse sites.
Analyses were conducted on 27 180 outpatients ≥6 months old presenting with an acute respiratory infection (ARI) with cough of ≤7-day duration during the 2011-2016 influenza seasons. A test-negative design was used with vaccination status defined as receipt of ≥1 dose of any influenza vaccine according to medical records, registries, and/or self-report. Influenza infection was determined by reverse-transcription polymerase chain reaction. VE estimates were calculated using odds ratios from multivariable logistic regression models adjusted for age, sex, race/ethnicity, time from illness onset to enrollment, high-risk conditions, calendar time, and vaccination status-site interaction.
For all sites combined, VE was statistically significant every season against all influenza and against the predominant circulating strains (VE = 19%-50%) Few differences among four sites in the US Flu VE Network were evident in five seasons. However, in 2015-16, overall VE in one site was 24% (95% CI = -4%-44%), while VE in two other sites was significantly higher (61%, 95% CI = 49%-71%; P = .002, and 53%, 95% CI = 33,67; P = .034).
With few exceptions, site-specific VE estimates aligned with each other and overall VE estimates. Observed VE may reflect inherent differences in community characteristics of the sites and highlights the importance of diverse settings for studying influenza vaccine effectiveness.

The Estudio Vacuna de Influenza Peru (VIP) cohort aims to describe the frequency of influenza virus infection, identify predictors of vaccine acceptance, examine the effects of repeated influenza vaccination on immunogenicity, and evaluate influenza vaccine effectiveness among HCP.
The VIP cohort prospectively followed HCP in Lima, Peru, during the 2016-2018 influenza seasons; a fourth year is ongoing. Participants contribute blood samples before and after the influenza season and after influenza vaccination (for vaccinees). Weekly surveillance is conducted to identify acute respiratory or febrile illnesses (ARFI). When an ARFI is identified, participants self-collect nasal swabs that are tested for influenza viruses by real-time reverse transcriptase-polymerase chain reaction. Influenza vaccination status and 5-year vaccination history are ascertained. We analyzed recruitment and enrollment results for 2016-2018 and surveillance participation for 2016-2017.
In the first 3 years of the cohort, VIP successfully contacted 92% of potential participants, enrolled 76% of eligible HCP, and retained >90% of participants across years. About half of participants are medical assistants (54%), and most provide \"hands-on\" medical care (76%). Sixty-nine percent and 52% of participants completed surveillance for >70% of weeks in years 1 and 2, respectively. Fewer weeks of completed surveillance was associated with older age (≥50 years), being a medical assistant, self-rated health of fair or poor, and not receiving the influenza vaccine during the current season (P-values < .05).
The VIP cohort provides an opportunity to address knowledge gaps about influenza virus infection, vaccination uptake, effectiveness and immunogenicity among HCP.

BACKGROUND: Influenza is a major cause of morbidity and mortality in the elderly worldwide. Influenza vaccination can prevent morbidity/mortality from influenza infection. A gap of 1-2 years, before an epidemic strain is recommended by the World Health Organization (WHO) to be the vaccine strain in Southeast Asia, has been reported; this results in a high rate of vaccine mismatch and excess influenza-associated morbidity. The aim of the current study was to evaluate the effect of repeated vaccination on vaccine effectiveness (VE) among the elderly in Taiwan, during years with and without early appearance of antigenically drifted strains.
METHODS: A historical cohort study was conducted to evaluate the impact of repeated vaccination on the reduction of influenza-associated hospitalization among persons older than 64 years over two influenza seasons: 2007-08, with all circulating virus strains mismatched, and 2008-09, with all virus strains matched with the vaccine strains, considering four exposure effects, namely current vaccine effect, sequential vaccination effect, residual protection effect and no vaccination effect. Propensity score matching on vaccination status was performed to ensure similar baseline characteristics between the groups that received and did not receive vaccination.
RESULTS: Only current-year vaccination in combination with prior history of annual revaccination significantly reduced the risk of hospitalization, with adjusted hazard ratios of 0.68 (95% CI: 0.54, 0.85) and 0.74 (95% CI: 0.57, 0.95) during the 2007-08 and 2008-09 influenza seasons, respectively. Further stratification showed that even during the 2007-08 influenza season, when all vaccinations were mismatched with the circulating strains, sequential vaccinations still significantly reduced influenza-associated hospitalization in the female population aged 68-74 and 75-84 years, with adjusted VE of 25.2% (95% CI: -9.6, 49.0%) and 36.9% (95% CI: 17.1, 52.0%), respectively.
CONCLUSIONS: Our study supports the recommendation of annual revaccination against influenza in the elderly, even though the circulating strain of influenza virus was antigenically mismatched with the vaccine strains.

Despite annual immunization, solid organ transplant (SOT) patients remain at increased risk for severe influenza infection because of suboptimal vaccine immunogenicity. We aimed to compare the CD4+ and CD8+ T-cell responses of the high-dose (HD) and the standard-dose (SD) trivalent inactivated vaccine.
We collected peripheral blood mononuclear cells pre- and postimmunization from 60 patients enrolled in a randomized trial of HD versus SD vaccine (30 HD; 30 SD) during the 2016-2017 influenza season.
The HD vaccine elicited significantly greater monofunctional and polyfunctional CD4+ and CD8+ T-cell responses against influenza A/H1N1, A/H3N2, and B. For example, median vaccine-elicited influenza-specific polyfunctional CD4+ T cells were higher in recipients of the HD than SD vaccine after stimulation with influenza A/H1N1 (1193 vs 0 per 106 CD4+ T cells; P = .003), A/H3N2 (1154 vs 51; P = .008), and B (1102 vs 0; P = .001). Likewise, vaccine-elicited influenza-specific polyfunctional CD8+ T cells were higher in recipients of the HD than SD vaccine after stimulation with influenza B (367 vs 0; P = .002).
Our study provides novel evidence that HD vaccine elicits greater cellular responses compared with the SD vaccine in SOT recipients, which provides support to preferentially consider use of HD vaccination in the SOT setting.