Evaluación de emergencia de una vacuna existente contra el virus de la fiebre aftosa tipo SAT2, aislado recientemente en Egipto en el 2018 / Emergency evaluation for existing vaccine against recently isolated Foot and mouth disease virus type SAT2 in Egypt 2018

El virus de la fiebre aftosa es un patógeno altamente infeccioso y contagioso. Recientemente, el topotipo VII, linaje Lib-12 del serotipo SAT2 se describió en brotes en Egipto durante 2018. La vacunación es una forma eficaz de controlar y combatir los brotes del virus de la fiebre aftosa, especialmente en áreas endémicas como Egipto. El presente estudio tuvo como objetivo evaluar la eficacia de la vacuna contra la fiebre aftosa que se produce actualmente, frente a la cepa de campo recientemente aislada del virus de la fiebre aftosa SAT2 topotipo VII, linaje Lib-12 (SAT2 Libia), mediante la aplicación de estudios in vitro e in vivo. Se inocularon en terneros, dos lotes de la vacuna actual contra el virus de la fiebre aftosa. A los 28 días posteriores a la vacunación, se recolectaron muestras de suero y se analizaron contra el virus de la fiebre aftosa SAT2 Libia adaptado a cultivo de tejidos y SAT2/EGY/2/2012 utilizando una prueba de neutralización viral para determinar la relación serológica (valor r1). El ensayo de reto en terneros vacunados se llevó a cabo empleando una cepa virulenta de la fiebre aftosa SAT2 Libia. Se encontró que los títulos de anticuerpos neutralizantes inducidos por los dos lotes de vacuna (1 y 2) y los de animales no vacunados, fueron 0,48, 0,39 y 0,15 log10 DICT50/mL, respectivamente, mientras que la prueba reveló valores de protección de 20 por ciento, 0 por ciento y 0 por ciento, respectivamente. Además, los valores de r1 fueron 0,195 y 0,186 para los lotes de vacuna (1 y 2), respectivamente. Se llegó a la conclusión de que los lotes de vacunas locales comerciales inactivadas disponibles actualmente (SAT2 SAT2/EGY/2/2012) no protegen a los terneros contra el virus circulante de la fiebre aftosa SAT2 topotipo VII, linaje Lib-12 que se aisló recientemente, por lo que es recomendable actualizar las vacunas existentes con la cepa aislada actualmente(AU)

Foot and mouth disease virus is a highly infectious and contagious pathogen. Recently the topotype VII, Lib‐12 lineage of serotype SAT2 was reported through outbreaks in Egypt during 2018. Vaccination is an effective way to control and combat the foot and mouth disease virus outbreaks especially in endemic areas like Egypt. The present study was aimed to evaluate the efficacy of the current produced foot and mouth disease vaccine, against the recently isolated field strain foot and mouth disease virus SAT2 topotype VII, Lib-12 lineage (SAT2 Libya), by applying in vitro and in vivo studies. Two batches of the current foot and mouth disease virus vaccine were inoculated in calves. At the 28th day post-vaccination serum samples were collected and tested against tissue culture adapted foot and mouth disease virus SAT2 Libya and SAT2/EGY/2/2012 using virus neutralization test to determine serological relationship (r1-value). The challenge test for vaccinated calves was carried out against the virulent foot and mouth disease virus SAT2 Libya. It was found that neutralizing antibody titers induced by the two vaccine batches (1 and 2) and those in unvaccinated animals were 0.48, 0.39 and 0.15 log10 TCID50/mL, respectively, while the challenge revealed protection values of 20 percent, 0 percent and 0 percent, respectively. Furthermore, the r1 values were 0.195 and 0.186 for vaccine batches (1 and 2), respectively. It was concluded that the available local commercial inactivated foot and mouth disease virus vaccine batches (SAT2 SAT2/EGY/2/2012) are unable to protect calves against the current circulating foot and mouth disease virus field isolate SAT2 topotype VII, Lib-12 lineage, thus it is highly recommended to update the existing vaccines with the present isolated strain(AU)

Evaluation of a COVID-19 Vaccine Campaign and SARS-CoV-2 Infection and Mortality Among Adults Aged 60 Years And Older in a Middle-Income Country.

Importance: Although there are reports of COVID-19 vaccine implementation in real-world populations, these come from high-income countries or from experience with messenger RNA technology vaccines. Data on outcomes of vaccine deployment in low- or middle-income countries are lacking. Objective: To assess whether the pragmatic application of the 3 COVID-19 vaccines available in Argentina, 2 of which have no reports of evaluation in real-world settings to date, were associated with a reduction in morbidity, all-cause mortality, and mortality due to COVID-19. Design, Setting, and Participants: This cohort study used individual and ecological data to explore outcomes following vaccination with rAd26-rAd5, ChAdOx1, and BBIBP-CorV. To correct for differences in exposure times, results are shown using incidence density per 100 000 person-days from the start of the vaccination campaign (December 29, 2020) to the occurrence of an event or the end of follow-up (May 15, 2021). Participants included 663 602 people aged at least 60 years residing in the city of Buenos Aires, Argentina. Statistical analysis was performed from June 1 to June 15, 2021. Main Outcomes and Measures: Diagnosis of COVID-19 confirmed by reverse transcription-polymerase chain reaction, death from all causes, and death within 30 days of a diagnosis of COVID-19. Poisson regression models were fitted to estimate associations with all 3 outcomes. Results: Among 663 602 residents of the city of Buenos Aires included in the study, 540 792 (81.4%) were vaccinated with at least 1 dose, with 457 066 receiving 1 dose (mean [SD] age, 74.5 (8.9) years; 61.5% were female [n = 281 284]; 68.0% [n = 310 987] received the rAd26-rAd5 vaccine; 29.5% [n = 135 036] received ChAdOx1; 2.4% [n = 11 043] received BBIBP-CorV) and 83 726 receiving 2 doses (mean [SD] age, 73.4 [6.8] years; 63.5% were female [n = 53 204]). The incidence density of confirmed COVID-19 was 36.25 cases/100 000 person-days (95% CI, 35.80-36.70 cases/100 000 person-days) among those who did not receive a vaccine, 19.13 cases/100 000 person-days (95% CI, 18.63-19.62 cases/100 000 person-days) among those who received 1 dose, and 4.33 cases/100 000 person-days (95% CI, 3.85-4.81 cases/100 000 person-days) among those who received 2 doses. All-cause mortality was 11.74 cases/100 000 person-days (95% CI, 11.51-11.96 cases/100 000 person-days), 4.01 cases/100 000 person-days (95% CI, 3.78-4.24 cases/100 000 person-days) and 0.40 cases/100 000 person-days (95% CI, 0.26-0.55 cases/100 000 person-days). COVID-19-related-death rate was 2.31 cases/100 000 person-days (95% CI, 2.19-2.42 cases/100 000 person-days), 0.59 cases/100 000 person-days (95% CI, 0.50-0.67 cases/100 000 person-days), and 0.04 cases/100 000 person-days (95% CI, 0.0-0.09 cases/100 000 person-days) among the same groups. A 2-dose vaccination schedule was associated with an 88.1% (95% CI, 86.8%-89.2%) reduction in documented infection, 96.6% (95% CI, 95.3%-97.5%) reduction in all-cause death, and 98.3% (95% CI, 95.3%-99.4%) reduction in COVID-19-related death. A single dose was associated with a 47.2% (95% CI, 44.2%-50.1%) reduction in documented infection, 65.8% (95% CI, 61.7%-69.5%) reduction in all-cause death, and 74.5% (95% CI, 66%-80.8%) reduction in COVID-19-related death. Conclusions and Relevance: This study found that within the first 5 months after the start of the vaccination campaign, vaccination was associated with a significant reduction in COVID-19 infection as well as a reduction in mortality.

Influence of adjuvants on the amount, specificity and functional activity of antibody response to human influenza vaccine in mice.

It's been almost a century since immunologists started using adjuvants as tools to develop more effective vaccines. Despite the rising number of adjuvanted vaccines in the last decades, we still lack knowledge of the adjuvants' effects on antibody response. This study was aimed to test the effect of immunizing mice with the human Inactivated Influenza vaccine (IIV), either alone or combined with different widely used adjuvants on the specific antibody response induced. Differential levels of IgM and IgG subclasses were found with the different adjuvants tested. Higher levels of antibodies did not always correspond with a higher efficacy to interfere with the virus infectivity. Differences in neutralization properties are possibly mediated by the specificity of the repertoire of antibodies induced. The repertoire was studied using a phage display 7-mer peptide library to screen for epitopes/mimotopes recognized by serum pools from vaccinated mice. The selected phage clones included peptides that corresponded to conformational mimotopes since they have no homology with lineal sequences of the Influenza strains' proteins. Five peptides were identified as recognized by sera from mice immunized with the IIV vaccine alone, including peptides from the hemagglutinin stalk domain, and by sera from mice immunized with the vaccine plus the different adjuvants employed. Adjuvants elicited a more diverse repertoire of epitope-recognizing antibodies that recognized epitopes of the HA recombinant globular head. Mimotopes were theoretically located at the neutralizing antigenic sites of the globular head of Influenza A H1N1pdm09, Influenza A H3N2, and Influenza B hemagglutinin. This study illustrates how different adjuvants can modify the extent and quality of humoral immunity against the IIV vaccine and the effectiveness of vaccination.

Home Administration of CVD 103-HgR: A Live Attenuated Oral Cholera Vaccine.

Vaccination is a well-established means for prevention and spread of disease in people traveling abroad. Although vaccines to diseases such as cholera are recommended by world health agencies, they are seldom required even when traveling to endemic regions. Consequences of noncompliance can affect traveler's health and spread diseases to new regions, as occurred in Haiti in 2010 when United Nations peacekeepers from Nepal, where a cholera outbreak was underway, introduced the disease to the region. Steps to increase vaccine recommendation compliance should therefore be an integral part of vaccine development. PXVX0200 contains Center for Vaccine Development 103-HgR live, attenuated recombinant Vibrio cholerae vaccine strain, and is indicated for single-dose immunization against the bacteria that causes cholera. It is supplied as one buffer and one active component packet to be mixed into water and ingested. Administration instructions are designed to be "user friendly" with flexibility for self-administration, thus promoting compliance. Studies to support self-administration were conducted to cover stability of the vaccine outside of normal storage conditions, potency in case of misadministration, and disposal procedures to minimize environmental impact. The principal findings showed that the stability of vaccine was maintained under conditions allowing for transport times and temperature conditions as well as when misadministration errors were made. Finally, the vaccine was effectively neutralized with hot water and soap to prevent bacterial environmental contamination in the event of an accidental spill. The conclusion is that PXVX0200 oral vaccine is stable, easy to formulate and dispose of, and is amenable to self-administration.

Potency evaluation of rabies vaccine for human use: The impact of reducing the number of animals per dilution - Part 2.

The most critical parameter for the quality control of the rabies vaccine is potency, which is evaluated by challenge test in mice while using a large animal number. Because the 3Rs concept is applied worldwide, it becomes necessary to develop alternative methods to demonstrate the production consistency of these vaccines and reduce the number of animals used for performing assays. Hence, the present study evaluated the impacts of reducing the number of mice used in the NIH test for such vaccines. A retrospective data analysis compared vaccines tested in the standard test with the results of the reduced test using only the first cages of each dilution and considering the second cages as their replicates. The relevance of the reduced assay was evaluated using Bland- Altman plot and CCC. Reliability was assessed by CV% and confidence intervals, while the impact of the reduced mouse number was evaluated by the analysis of the confidence interval of potency results and regression, linearity and parallelism parameters. The results demonstrated the feasibility of reducing to eight mice per dilution in routine assays, with complete statistical validation of the resulting potency, allowing the number of animals used for the test vaccines to be reduced by 50%.

Prospective cohort study of influenza vaccine effectiveness among healthcare personnel in Lima, Peru: Estudio Vacuna de Influenza Peru, 2016-2018.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: The VIP cohort provides an opportunity to address knowledge gaps about influenza virus infection, vaccination uptake, effectiveness and immunogenicity among HCP.

Using Protozoan Surface Proteins for Effective Oral Vaccination.

The Global Vaccine Action Plan of the World Health Organization (WHO) calls for nonsyringe delivery mechanisms, thermostable vaccines, and new bioprocessing technologies as priority research areas. Here we discuss the use of protozoan surface proteins to develop a safe, stable, and efficient versatile oral vaccine platform.

Heterogeneity in influenza seasonality and vaccine effectiveness in Australia, Chile, New Zealand and South Africa: early estimates of the 2019 influenza season.

We compared 2019 influenza seasonality and vaccine effectiveness (VE) in four southern hemisphere countries: Australia, Chile, New Zealand and South Africa. Influenza seasons differed in timing, duration, intensity and predominant circulating viruses. VE estimates were also heterogeneous, with all-ages point estimates ranging from 7-70% (I2: 33%) for A(H1N1)pdm09, 4-57% (I2: 49%) for A(H3N2) and 29-66% (I2: 0%) for B. Caution should be applied when attempting to use southern hemisphere data to predict the northern hemisphere influenza season.

Pneumococcal conjugate vaccine against serotype 3 pneumococcal pneumonia in adults: A systematic review and pooled analysis.

BACKGROUND: Serotype 3 pneumococcal disease has not substantially declined at the population level after the routine introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into pediatric immunization programs across the globe. This epidemiological finding has generated debate regarding the effectiveness of PCV13 against serotype 3 disease. Evaluating PCV13 effectiveness against serotype 3 is especially critical in adults, where serotype 3 makes up an important amount of remaining pneumococcal disease. METHODS: We performed a systematic review of the published literature to assess the direct effectiveness of PCV13 against serotype 3 community-acquired pneumonia (CAP) among adults. We then estimated overall vaccine effectiveness (VE) using a pooled analysis of the individual-level, raw data. RESULTS: Two published studies met inclusion criteria. One was a randomized controlled trial conducted in the Netherlands and published in 2014. The other was a recently-published case-control study conducted in Louisville, Kentucky that used a test-negative design (TND). We also identified a third TND study conducted in Argentina that was recently presented as a conference abstract but is not yet published. All three studies were conducted in adults aged ≥65 years. PCV13 VE against serotype 3 hospitalized CAP was 52.5% (95%CI: 6.2-75.9%) from the pooled analysis of individual-level data from all three studies. Results were similar if the unpublished estimate was excluded (serotype 3 VE = 53.6% [95%CI: 6.7-76.9%]). No heterogeneity was observed. CONCLUSIONS: Currently-available evidence, although limited to three studies, suggests that PCV13 provides direct protection against serotype 3 hospitalized CAP in adults aged ≥65 years.

Remarks on the possibility of introducing the fractionated dose of the inactivated poliomyelitis vaccine in the Latin American Child Immunization Schedule.

Given that the last notified case of poliomyelitis due to wild poliovirus type 2 was in 1999, in 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) recommended the withdrawal of the type 2 component of oral polio vaccine (OPV) and the introduction of a bivalent OPV (bOPV) in all countries by 2016. WHO recommended also that the withdrawal should be preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunization schedules. The introduction of IPV prior to the change of the bOPV in 2016 to trivalent OPV (tOPV) was based on the concept of ensuring that a substantial proportion of the population would be protected against type 2 polio after the removal of the type 2 OPV. However, the world's two producers of IPV (Bilthoven Biologicals and Sanofi) have faced problems in the production of this vaccine and therefore reported a reduction of the global supply of IPV. In response to the potential shortage of IPV, at a meeting held on March 10 2017, the SAGE and Technical Advisory Group (TAG) of the Pan American Health Organization (PAHO) urged the countries in the Latin American region to replace the routine administration of the full doses of inactivated polio vaccine (IPV-C) in the immunization schedule (administered by intramuscular route), administering a fraction of the full dose in two intradermal shots (IPV-f). The possibility of this strategy was analyzed by opinion leaders convened by the Paraguayan Society of Pediatrics with the support of the Latin American Society of Pediatric Infectious Diseases (SLIPE) and Latin American Association of Pediatrics (ALAPE). This document presents the results of the discussion.

Remarks on the possibility of introducing the fractionated dose of the inactivated poliomyelitis vaccine in the Latin American Child Immunization Schedule

Abstract Given that the last notified case of poliomyelitis due to wild poliovirus type 2 was in 1999, in 2012, the Strategic Advisory Group of Experts on Immunization (SAGE) of the World Health Organization (WHO) recommended the withdrawal of the type 2 component of oral polio vaccine (OPV) and the introduction of a bivalent OPV (bOPV) in all countries by 2016. WHO recommended also that the withdrawal should be preceded by the introduction of at least one dose of inactivated poliovirus vaccine (IPV) in routine immunization schedules. The introduction of IPV prior to the change of the bOPV in 2016 to trivalent OPV (tOPV) was based on the concept of ensuring that a substantial proportion of the population would be protected against type 2 polio after the removal of the type 2 OPV. However, the world's two producers of IPV (Bilthoven Biologicals and Sanofi) have faced problems in the production of this vaccine and therefore reported a reduction of the global supply of IPV. In response to the potential shortage of IPV, at a meeting held on March 10 2017, the SAGE and Technical Advisory Group (TAG) of the Pan American Health Organization (PAHO) urged the countries in the Latin American region to replace the routine administration of the full doses of inactivated polio vaccine (IPV-C) in the immunization schedule (administered by intramuscular route), administering a fraction of the full dose in two intradermal shots (IPV-f). The possibility of this strategy was analyzed by opinion leaders convened by the Paraguayan Society of Pediatrics with the support of the Latin American Society of Pediatric Infectious Diseases (SLIPE) and Latin American Association of Pediatrics (ALAPE). This document presents the results of the discussion.

Métodos alternativos como parte de las nuevas tendencias en el control de calidad de vacunas / Alternative methods as part of the new trends in vaccine quality control

El control de calidad de las vacunas resulta fundamental para las actividades de producción, liberación lote a lote y comercialización de las vacunas. Sin embargo, en la actualidad este es un proceso que por su concepción es lento y costoso debido a que se apoya en la realización de extensas pruebas en animales para demostrar la potencia y seguridad de estos productos biológicos. El desarrollo de métodos alternativos inspirados en el principio de las 3Rs (Reducción, Refinamiento y Reemplazo) constituye una tendencia que debe impactar de manera muy significativa en la reducción de los tiempos de liberación y el costo del proceso de control de calidad de vacunas en los próximos años. En particular la sustitución de las pruebas de potencia y toxicidad in vivo por procedimientos alternativos más relevantes, rápidos, exactos, reproducibles, robustos y baratos, que incluyen la serología, la cuantificación directa de antígeno, los ensayos en cultivos celulares y el enfoque a consistencia, por solo mencionar algunos; implica un cambio de paradigma, con indiscutibles repercusiones éticas, logísticas, económicas y científico-técnicas, para el aseguramiento de los parámetros de calidad de los inmunobiológicos con el mejor balance costo-beneficio: las vacunas. Los fundamentos técnicos de estos métodos alternativos, sus ventajas y nivel de implementación a nivel internacional, así como sus principales limitaciones, son abordados en este trabajo(AU)

Vaccine quality control is crucial for the manufacturing, lot release and commercialization activities worldwide. However, the current process is by-design too slow and expensive because is based on large animal assays for assuring the potency and safety of these important biological products. The development of 3Rs alternative methods (Reduction, Refinement and Replacement) is a trend able to significantly reduce the releasing times and costs of the vaccine quality control processes in the next few years. Particularly, the replacement of the animals-based potency and toxicity assays by alternative procedures more relevant, fast, accurate, reproducible and cheap, including serology, direct antigen quantification, cell culture tests and the Consistency Approach, for just mentioning some of them, implies a paradigm shift, with undisputable ethical, logistical, economic, scientific and technical repercussions for ensuring the vaccine quality parameters. Theoretical basements, advantages and implementation levels of the alternatives methods as well as their main limitations are presented in this paper(AU)

A Randomized, Placebo-Controlled Trial of the Quadrivalent Human Papillomavirus Vaccine in Human Immunodeficiency Virus-Infected Adults Aged 27 Years or Older: AIDS Clinical Trials Group Protocol A5298.

Background: Adults living with human immunodeficiency virus (HIV) are at increased risk for anal and oropharyngeal cancer caused by human papillomavirus (HPV). The efficacy of HPV vaccines in this population is unknown. Methods: In this phase 3, double-blind, randomized, controlled trial, we assigned HIV-infected adults aged ≥27 years to the quadrivalent HPV (types 6, 11, 16, 18) vaccine or placebo (1:1) stratified by sex and presence of anal high-grade squamous intraepithelial lesions on biopsy (bHSIL). The primary endpoint was vaccine efficacy against incident persistent anal infection with quadrivalent vaccine types or single detection at the final visit that were not present at baseline. Secondary endpoints included vaccine efficacy for anal bHSIL after week 52, persistent oral HPV infection. Results: A total of 575 participants were randomized. The Data and Safety Monitoring Board stopped the study early due to futility. Vaccine efficacy was 22% (95.1% confidence interval [CI], -31%, 53%) for prevention of persistent anal infection or single detection at the final visit, 0% (95% CI -44%, 31%) for improving bHSIL outcomes and 88% (95.1% CI 2%, 98%) for preventing persistent oral HPV infection, but was 32% (95.1% CI -80%, 74%) for 6-month persistent oral HPV infection or single detection at the final visit. Conclusions: These results do not support HPV vaccination of HIV-infected adults aged ≥27 years to prevent new anal HPV infections or to improve anal HSIL outcomes. However, our data suggest a role for prevention of oral HPV infections, but this finding should be confirmed in future studies. Clinical Trials Registration: NCT01461096.

Effect of Age at Vaccination on Rotavirus Vaccine Effectiveness in Bolivian Infants.

BACKGROUND: Rotavirus vaccines are less effective in developing countries versus developed countries. One hypothesis for this difference in performance is that higher levels of maternal antibodies in developing countries may interfere with vaccine response, suggesting that delayed dosing could be beneficial. The present analysis aims to assess whether rotavirus vaccine effectiveness (VE) varies by age at vaccination during routine use in Bolivia. METHODS: Data were merged from 2 postlicensure evaluations of monovalent rotavirus vaccine (RV1) in Bolivia, where 2 doses of RV1 are recommended at 2 and 4 months of age. For each dose, children were classified as receiving each dose "early," "on-time" or "late." Stratified unconditional logistic regression models were used to estimate VE, using unvaccinated children as the referent. VE was calculated as (1 - odds ratio) × 100%. Models were adjusted for hospital, age and time since RV1 introduction (via including terms for month and year of birth). RESULTS: VE for 2 doses of RV1 tended to be higher in infants receiving the first dose early (VE, 92%; 95% confidence interval: 70%-98%), when compared with infants receiving their first dose on-time [72% (62%-81%)] or late [68% (51%-79%)]. Estimates of VE were not substantially different when comparing children by age at second dose [early: VE, 76% (50%-89%); on-time: VE, 70% (50%-89%); late: VE, 75% (60%, 84%)], including all children. CONCLUSIONS: Our results indicate that early administration may improve VE and support the current World Health Organization recommendations for the RV1 schedule.

A deeper mining on the protein composition of VA-MENGOC-BC®: An OMV-based vaccine against N. meningitidis serogroup B and C.

The protein composition of an Outer Membrane Vesicle (OMV) preparation that constitutes the active pharmaceutical ingredient of VA-MENGOC-BC®, an effective vaccine against Neisseria meningitidis serogroups B, and C is presented. This preparation has a high lipid content and five abundant membrane proteins (FetA, PorA, PorB, RmpM, and Opc), constituting approximately 70% of the total protein mass. The protein composition was determined by combining the use of the Hexapeptide Ligand Library and an orthogonal tandem fractionation of tryptic peptides by reverse-phase chromatography at alkaline and acid pH. This approach equalizes the concentration of tryptic peptides derived from low- and high-abundance proteins as well as considerably simplifying the number of peptides analyzed by LC-MS/MS, enhancing the possibility of identifying low-abundance species. Fifty-one percent of the proteins originally annotated as membrane proteins in the genome of the MC58 strain were identified. One hundred and sixty-eight low-abundance cytosolic proteins presumably occluded within OMV were also identified. Four (NadA, NUbp, GNA2091, and fHbp), out of the five antigens constituting the Bexsero® vaccine, were detected in this OMV preparation. In particular, fHbp is also the active principle of the Trumenba® vaccine developed by Pfizer. The HpuA and HpuB gene products (not annotated in the MC58 genome) were identified in the CU385 strain, a clinical isolate that is used to produce this OMV. Considering the proteins identified here and previous work done by our group, the protein catalogue of this OMV preparation was extended to 266 different protein species.

Influenza seasonality goes south in the Yucatan Peninsula: The case for a different influenza vaccine calendar in this Mexican region.

INTRODUCTION: While vaccination may be relatively straightforward for regions with a well-defined winter season, the situation is quite different for tropical regions. Influenza activity in tropical regions might be out of phase with the dynamics predicted for their hemispheric group thereby impacting the effectiveness of the immunization campaign. OBJECTIVE: To investigate how the climatic diversity of Mexico hinders its existing influenza immunization strategy and to suggest that the hemispheric vaccine recommendations be tailored to the regional level in order to optimize vaccine effectiveness. METHODS: We studied the seasonality of influenza throughoutMexico by modeling virological and mortality data.De-trended time series of each Mexican state were analyzed by Fourier decomposition to describe the amplitude and timing of annual influenza epidemic cycles and to compare with each the timing of the WHO's Northern and Southern Hemispheric vaccination schedule. FINDINGS: The timings of the primary (major) peaks of both virological and mortality data for most Mexican states are well aligned with the Northern Hemisphere winter (December-February) and vaccine schedule. However, influenza peaks in September in the three states of the Yucatan Peninsula. Influenza-related mortality also peaks in September in Quintana Roo and Yucatan whereas it peaks in May in Campeche. As the current timing of vaccination in Mexico is between October and November, more than half of the annual influenza cases have already occurred in the Yucatan Peninsula states by the time the Northern Hemispheric vaccine is delivered and administered. CONCLUSION: The current Northern Hemispheric influenza calendar adopted for Mexico is not optimal for the Yucatan Peninsula states thereby likely reducing the effectiveness of the immunization of the population. We recommend that Mexico tailor its immunization strategy to better reflect its climatologic and epidemiological diversity and adopt the WHO Southern Hemisphere influenza vaccine and schedule for the Yucatan Peninsula.

The corn smut-made cholera oral vaccine is thermostable and induces long-lasting immunity in mouse.

The use of corn smut for the production of recombinant vaccines has been recently implemented by our group. In this study, the stability and immunogenic properties of the corn smut-based cholera vaccine, based on the cholera toxin B subunit (CTB), were determined in mouse. The immunogenic potential of distinct corn smut CTB doses ranging from 1 to 30µg were assessed, with maximum humoral responses at both the systemic (IgG) and intestinal (IgA) levels at a dose of 15µg. The humoral response last for up to 70days after the third boost. Mice were fully protected against a challenge with cholera toxin after receiving three 15µg-doses. Remarkably, the corn smut-made vaccine retained its immunogenic activity after storage at room temperature for a period of 1year and no reduction on CTB was observed following exposure at 50°C for 2h. These data support the use of the corn smut-made CTB vaccine as a highly stable and effective immunogen and justify its evaluation in target animal models, such as piglet and sheep, as well as clinical evaluations in humans.

Sustained Effectiveness of Rotavirus Vaccine Against Very Severe Rotavirus Disease Through the Second Year of Life, Bolivia 2013-2014.

BACKGROUND: In Bolivia, monovalent rotavirus vaccine was introduced in 2008 and a previous evaluation reported a vaccine effectiveness (VE) of 77% with 2 doses of vaccine in children aged <3 years. This evaluation sought to determine if rotavirus vaccine provided protection through the second year of life against circulating genotypes. METHODS: A case-control study was performed in 5 hospitals from April 2013 to March 2014. Among enrolled participants who met study criteria and had rotavirus stool testing performed and vaccine status confirmed, we calculated VE using a logistic regression model. Subgroup analyses were performed among children aged <1 year and those aged ≥1 year, among children with severe diarrhea (Vesikari score ≥11) and very severe diarrhea (Vesikari score ≥15), and among G and P strains with at least 40 specimens. RESULTS: A total of 776 children were enrolled. For children <1 year and ≥1 year of age with severe diarrhea, VE for 2 doses was 75% (95% confidence interval [CI], 46%-88%) and 53% (95% CI, 9%-76%), respectively. For children <1 year and ≥1 year of age with very severe diarrhea, VE for 2 doses was 80% (95% CI, 44%-93%) and 74% (95% CI, 35%-90%), respectively. Genotype-specific analysis demonstrated similar VE for the 4 most common G and P types (G3, G9, P[6] and P[8]). CONCLUSIONS: A monovalent rotavirus vaccine remains effective against a broad range of circulating strains as part of a routine immunization program >5 years after its introduction in Bolivia. Although VE appears to wane in children aged ≥1 year, it still provides significant protection, and does not wane against severe disease.

Effectiveness of Monovalent and Pentavalent Rotavirus Vaccines in Guatemala.

BACKGROUND: Concerns remain about lower effectiveness and waning immunity of rotavirus vaccines in resource-poor populations. We assessed vaccine effectiveness against rotavirus in Guatemala, where both the monovalent (RV1; 2-dose series) and pentavalent (RV5; 3-dose series) vaccines were introduced in 2010. METHODS: A case-control evaluation was conducted in 4 hospitals from January 2012 to August 2013. Vaccine status was compared between case patients (children with laboratory-confirmed rotavirus diarrhea) and 2 sets of controls: nondiarrhea "hospital" controls (matched by birth date and site) and nonrotavirus "test-negative" diarrhea controls (adjusted for age, birth month/year, and site). Vaccine effectiveness ([1 - odds ratio of vaccination] × 100%) was computed using logistic regression models. RESULTS: We evaluated 213 case patients, 657 hospital controls, and 334 test-negative controls. Effectiveness of 2-3 doses of a rotavirus vaccine against rotavirus requiring emergency department visit or hospitalization was 74% (95% confidence interval [CI], 58%-84%) with hospital controls, and 52% (95% CI, 26%-69%) with test-negative controls. Using hospital controls, no significant difference in effectiveness was observed between infants 6-11 months (74% [95% CI, 18%-92%]) and children ≥12 months of age (71% [95% CI, 44%-85%]) (P= .85), nor between complete courses of RV1 (63% [95% CI, 23%-82%]) and RV5 (69% [95% CI, 29%-87%]) (P= .96). An uncommon G12P[8] strain, partially heterotypic to strains in both vaccines, was identified in 89% of cases. CONCLUSIONS: RV1 and RV5 were similarly effective against severe rotavirus diarrhea caused by a heterotypic strain in Guatemala. This supports broader implementation of rotavirus vaccination in low-income countries where >90% global deaths from rotavirus occur.