High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity.

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer.

Respiratory syncytial virus vaccination and immunoprophylaxis: realising the potential for protection of young children.

The search for safe and efficacious products to prevent severe respiratory syncytial virus (RSV) disease in young infants has lasted more than 60 years. In high-income and middle-income countries, two new products have been authorised: an RSV monoclonal antibody for administration to infants (nirsevimab) and an RSV prefusion F maternal vaccine (RSVpreF [Pfizer, Puurs, Belgium]) for administration to pregnant people. These products are not yet available in low-income and lower-middle-income countries, where most RSV deaths occur. Other papers in this Series describe the acute burden of RSV disease in young children, the effects of RSV infection in early childhood on long-term lung health, and the burden of RSV disease and disease prevention products in older adults. In this Series paper, we briefly review the efficacy, effectiveness, and safety of nirsevimab and RSVpreF maternal vaccine for protection of infants. We then explore potential regulatory, policy, and implementation pathways and provide case studies of intervention uptake in Spain and Argentina, and considerations for use in Kenya. We also explore the health economic evidence to inform product introduction decisions. With sufficient political will and affordable pricing, RSV disease prevention in infants can become a global reality.

Effectiveness of rAd26-rAd5, ChAdOx1 nCoV-19, and BBIBP-CorV vaccines for risk of infection with SARS-CoV-2 and death due to COVID-19 in people older than 60 years in Argentina: a test-negative, case-control, and retrospective longitudinal study.

BACKGROUND: In January, 2021, a vaccination campaign against COVID-19 was initiated with the rAd26-rAd5, ChAdOx1 nCoV-19, and BBIBP-CorV vaccines in Argentina. The objective of this study was to estimate vaccine effectiveness at reducing risk of SARS-CoV-2 infection and COVID-19 deaths in people older than 60 years. METHODS: In this test-negative, case-control, and retrospective longitudinal study done in Argentina, we evaluated the effectiveness of three vaccines (rAd26-rAd5, ChAdOx1 nCoV-19, and BBIBP-CorV) on SARS-CoV-2 infection and risk of death in people with RT-PCR confirmed COVID-19, using data from the National Surveillance System (SNVS 2.0). All individuals aged 60 years or older reported to SNVS 2.0 as being suspected to have COVID-19 who had disease status confirmed with RT-PCR were included in the study. Unvaccinated individuals could participate in any of the analyses. People with suspected COVID-19 who developed symptoms before the start of the implementation of the vaccination programme for their age group or district were excluded from the study. The odds ratio of SARS-CoV-2 infection was evaluated by logistic regression and the risk of death in individuals with RT-PCR confirmed COVID-19 was evaluated by proportional hazard regression models, adjusted for possible confounders: age at the time of the symptom onset date, sex, district of residence, epidemiological week corresponding to the symptom onset date, and history of COVID-19. The estimation of vaccine effectiveness to prevent death due to COVID-19 was done indirectly by combining infection and death estimates. In addition, we evaluated the effect of the first dose of viral vector vaccines across time. FINDINGS: From Jan 31, to Sept 14, 2021, 1 282 928 individuals were included, of whom 687 167 (53·6%) were in the rAd26-rAd5 analysis, 358 431 (27·6%) in the ChAdOx1 nCoV-19 analysis, and 237 330 (18·5%) in the BBIBP-CorV analysis. Vaccine effectiveness after two doses was high for all three vaccines, adjusted odds ratio 0·36 (95% CI 0·35-0·37) for rAd26-rAd5, 0·32 (0·31-0·33) for ChAdOx1 nCoV-19, and 0·56 (0·55-0·58) for BBIBP-CorV. After two doses, the effect on deaths was higher than that on risk of infection: adjusted hazard ratio 0·19 (95% CI 0·18-0·21) for rAd26-rAd5, 0·20 (0·18-0·22) for ChAdOx1 nCoV-19, and 0·27 (0·25-0·29) for BBIBP-CorV. The indirectly estimated effectiveness on deaths was 93·1% (95% CI 92·6-93·5) for rAd26-rAd5, 93·7% (93·2-94·3) for ChAdOx1 nCoV-19, and 85·0% (84·0-86·0) for BBIBP-CorV following two doses. First dose effect of viral vector vaccines remained stable over time. INTERPRETATION: The vaccines used in Argentina showed effectiveness in reducing infection and death by SARS-CoV-2 and COVID-19. FUNDING: None.

Immune response to co-administration of measles, mumps, and rubella (MMR), and yellow fever vaccines: a randomized non-inferiority trial among one-year-old children in Argentina.

BACKGROUND: In yellow fever (YF) endemic areas, measles, mumps, and rubella (MMR), and YF vaccines are often co-administered in childhood vaccination schedules. Because these are live vaccines, we assessed potential immune interference that could result from co-administration. METHODS: We conducted an open-label, randomized non-inferiority trial among healthy 1-year-olds in Misiones Province, Argentina. Children were randomized to one of three groups (1:1:1): Co-administration of MMR and YF vaccines (MMR1YF1), MMR followed by YF vaccine four weeks later (MMR1YF2), or YF followed by MMR vaccine four weeks later (YF1MMR2). Blood samples obtained pre-vaccination and 28 days post-vaccination were tested for immunoglobulin G antibodies against measles, mumps, and rubella, and for YF virus-specific neutralizing antibodies. Non-inferiority in seroconversion was assessed using a -5% non-inferiority margin. Antibody concentrations were compared with Kruskal-Wallis tests. RESULTS: Of 851 randomized children, 738 were correctly vaccinated, had ≥ 1 follow-up sample, and were included in the intention-to-treat population. Non-inferior seroconversion was observed for all antigens (measles seroconversion: 97.9% in the MMR1YF1 group versus 96.3% in the MMR1YF2 group, a difference of 1.6% [90% CI -1.5, 4.7]; rubella: 97.9% MMR1YF1 versus 94.7% MMR1YF2, a difference of 3.3% [-0.1, 6.7]; mumps: 96.7% MMR1YF1 versus 97.9% MMR1YF2, a difference of -1.3% [-4.1, 1.5]; and YF: 96.3% MMR1YF1 versus 97.5% YF1MMR2, a difference of -1.2% [-4.2, 1.7]). Rubella antibody concentrations and YF titers were significantly lower following co-administration; measles and mumps concentrations were not impacted. CONCLUSION: Effective seroconversion was achieved and was not impacted by the co-administration, although antibody levels for two antigens were lower. The impact of lower antibody levels needs to be weighed against missed opportunities for vaccination to determine optimal timing for MMR and YF vaccine administration. TRIAL REGISTRATION: The study was retrospectively registered in ClinicalTrials.gov (NCT03368495) on 11/12/2017.

Baseline prevalence and type distribution of Human papillomavirus in sexually active non-vaccinated adolescent girls from Argentina.

In 2011, Argentina launched a government-funded national Human papillomavirus (HPV) immunization program incorporating a bivalent HPV vaccine, with a 0-1-6-month schedule, for girls 11 years of age, born after January 2000. Monitoring the changes of HPV infection prevalence among young women has been proposed as an endpoint for early assessment of HPV vaccination programs. However, the data on HPV prevalence at young ages are very limited. The aim of this work was to determine the prevalence of HPV infection and type-specific distribution in sexually active 15-17-year-old non-vaccinated girls. Cervical samples from 1073 adolescents were collected for HPV detection and genotyping using the BSGP5+/GP6+PCR-reverse line blot (RLB) assay. Out of 957 specimens analyzed, 56.3% were positive for any HPV type; 42.2% harbored at least one high-risk HPV (HR-HPV) type and 30.8% low-risk HPV (LR-HPV) types. Multiple and single infections were identified in 36.3% and 20.0% of the samples respectively. The 6 most common HR-HPV types were HPV16 (11.1%), HPV52 (10.8%), HPV56 (8.3%), HPV51 (7.4%), HPV58 (7.3%) and HPV31 (7.1%). The prevalence of HR-HPV-16/18 was 15.2%. In conclusion, results confirm that HPV (particularly HR-types) are very common among sexually active adolescents, and prevalence rises quickly after their sexual debut. Our HPV type-specific prevalence baseline may be used to monitor post-vaccinal longitudinal changes in Argentina.

Maternal Vaccination in Argentina: Tetanus, Diphtheria, and Acellular Pertussis Vaccine Effectiveness During Pregnancy in Preventing Pertussis in Infants <2 Months of Age.

BACKGROUND: In 2011, Argentina experienced its highest pertussis incidence and mortality rates of the last decade; 60% of deaths were among infants aged <2 months. In response, a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine was recommended for all pregnant women at ≥20 weeks of gestation. Although recent studies suggest that maternal Tdap vaccination is effective at preventing infant disease, no data have come from low- or middle-income countries, nor from ones using whole-cell pertussis vaccines for primary immunization. METHODS: We conducted a matched case-control evaluation to assess the effectiveness of maternal Tdap vaccination in preventing pertussis among infants aged <2 months in Argentina. Pertussis case patients identified from September 2012 to March 2016 at 6 hospital sites and confirmed by polymerase chain reaction testing were included. Five randomly selected controls were matched to each case patient by hospital site and mother's health district. We used multivariable conditional logistic regression to calculate odds ratios (ORs). Vaccine effectiveness (VE) was estimated as (1 - OR) × 100%. RESULTS: Seventy-one case patients and 300 controls were included in the analysis. Forty-nine percent of case patients and 78% of controls had mothers who were vaccinated during pregnancy. Overall Tdap VE was estimated at 80.7% (95% confidence interval, 52.1%-92.2%). We found similar VE whether Tdap was administered during the second or third trimester. CONCLUSIONS: Tdap vaccination during pregnancy is effective in preventing pertussis in infants aged <2 months in Argentina, with similar effectiveness whether administered during the second or third trimester of pregnancy.

Community acquired pneumonia incidence among children less than 5 years of age in Concordia, Argentina: vaccination impact.

OBJECTIVE: To measure the effectiveness of pneumococcal conjugated vaccine (PCV13) against Community Acquired Pneumonia (CAP) and invasive pneumococcal disease, 2 years after the vaccine (2+1) was included into the National Immunization Program of Argentina, and to describe variables associated with bacterial pneumonia and hospitalization. METHODS: This was a prospective, population-based surveillance study of CAP incidence (ambulatory and hospitalized) among children less than 5 years of age in the Department of Concordia (Entre Rios, Argentina) from April 2014 - March 2016. The diagnosis of probable bacterial pneumonia (PBP) was determined following the standardized WHO protocol. Incidence during the post-vaccine introduction period was compared with the results from a previous study that used similar methodology for the pre-PCV13 introduction period from 2002 - 2005. RESULTS: During the study period, 330 patients had a clinical diagnosis of CAP, of which 92 were PBP (6 with pleural effusion). S. pneumoniae was not isolated from any sample. No factors associated with PBP were found in multivariable analysis. The decrease in PBP and pleural effusion was significant in relation to the previous study: 63% (P < 0.0001) and 80.9% (P < 0.003), respectively. PCV13 uptake was 97.3% for the 1st dose and 84.8% for the booster dose. CONCLUSIONS: PCV13 was effective to reduce incidence of consolidated pneumonia and pleural effusion, among children less than 5 years of age in Concordia, Argentina. Vaccination is a very effective public health strategy for reducing vaccine preventable diseases, with impact on burden of disease and hospitalization.

Vaccination Recommendations for Adults With Autoimmune Inflammatory Rheumatic Diseases in Latin America.

BACKGROUND/OBJECTIVE: Patients with autoimmune inflammatory rheumatic diseases (AIRDs) are at increased risk of contracting severe infections and suffering complications, particularly when they are receiving immunomodulating therapy. Vaccination is an important means to prevent many potential infections and thereby reduce the morbidity and mortality associated with AIRD. The purpose of this consensus document is to provide health care professionals with recommendations for the vaccination of AIRD patients who reside in Latin America. The recommendations were developed by an expert committee from the region based on a review of the literature and their clinical experience. METHODS: The Americas Health Foundation (AHF) used PubMed and EMBASE to identify clinicians and scientists with an academic or hospital affiliation and who had published in the field of adult vaccination and rheumatic diseases since 2010. As a result of this effort, AHF convened an 8-member panel of clinical and scientific experts from Latin America. Both the AHF and panel members conducted a careful literature review to identify relevant publications in the areas of adult vaccination and rheumatology, and the sum of the articles identified was provided to the entire panel. Prior to the conference, panelists were each asked to prepare a written response to a salient issue on the subject, identified by AHF. RESULTS AND CONCLUSIONS: During the conference, each response was edited by the entire group, through numerous drafts and rounds of discussion until a complete consensus on vaccination recommendations for adult patients with AIRDs was obtained, including 7 key recommendations.

[Assessment of the use in adults of four vaccines: a population survey in Argentina]. / Evaluación del uso en adultos de cuatro vacunas: una encuesta poblacional en Argentina.

Vaccination is one of the most effective strategies for disease prevention. Argentina initiated the transition from child vaccination to family vaccination through the incorporation of an adult schedule. One of the difficulties with this last group is to assess the percentage of use (PU) of the vaccines. With the aim of determining the PU of adult vaccines in Argentina, a vaccination module was included in the National Survey of Risk Factors carried out in 2013 by the National Ministry of Health. The sampling had a stratified multistage design. A total of 32 365 people = 18 year-old were surveyed about the use of four vaccines included in the National Vaccination Calendar: hepatitis B, tetanus, influenza, and pneumococcus. The entire population was surveyed for tetanus and hepatitis B while certain groups at risk were evaluated for influenza and pneumococcus, according to current recommendations. PU varied according to the vaccine analyzed: tetanus 49.8%, hepatitis B 21.7%, influenza 51.6% and pneumococcus 16.2%. The main information sources on adult vaccination were media (television, internet, etc.) followed by health personnel (70.8% and 27.9%, respectively). The survey is a suitable tool to assess the use of vaccines by adults, identify low coverage populations, and to plan and implement strategies to improve coverage.

Genetic characterization and estimated 4CMenB vaccine strain coverage of 284 Neisseria meningitidis isolates causing invasive meningococcal disease in Argentina in 2010-2014.

Meningococcal (Neisseria meningitidis) serogroup B (MenB) strain antigens are diverse and a limited number of strains can be evaluated using the human serum bactericidal antibody (hSBA) assay. The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict the likelihood of coverage for large numbers of isolates by the 4CMenB vaccine, which includes antigens Neisseria adhesin A (NadA), Neisserial Heparin-Binding Antigen (NHBA), factor H-binding protein (fHbp), and Porin A (PorA). In this study, we characterized by whole-genome analyses 284 invasive MenB isolates collected from 2010 to 2014 by the Argentinian National Laboratories Network (52-61 isolates per year). Strain coverage was estimated by gMATS on all isolates and by hSBA assay on 74 randomly selected isolates, representative of the whole panel. The four most common clonal complexes (CCs), accounting for 81.3% of isolates, were CC-865 (75 isolates, 26.4%), CC-32 (59, 20.8%), CC-35 (59, 20.8%), and CC-41/44 (38, 13.4%). Vaccine antigen genotyping showed diversity. The most prevalent variants/peptides were fHbp variant 2, NHBA peptides 24, 21, and 2, and PorA variable region 2 profiles 16-36 and 14. The nadA gene was present in 66 (23.2%) isolates. Estimated strain coverage by hSBA assay showed 78.4% of isolates were killed by pooled adolescent sera, and 51.4% and 64.9% (based on two different thresholds) were killed by pooled infant sera. Estimated coverage by gMATS (61.3%; prediction interval: 55.5%, 66.7%) was consistent with the infant hSBA assay results. Continued genomic surveillance is needed to evaluate the persistence of major MenB CCs in Argentina.

The most common clinical manifestations of invasive meningococcal disease include meningitis and septicemia, which can be deadly, and many survivors suffer long-term serious after-effects. Most cases of invasive meningococcal disease are caused by six meningococcal serogroups (types), including serogroup B. Although vaccines are available against meningococcal serogroup B infection, these vaccines target antigens that are highly diverse. Consequently, the effectiveness of vaccination may vary from country to country because the meningococcal serogroup B strains circulating in particular regions carry different forms of the target vaccine antigens. This means it is important to test serogroup B strains isolated from specific populations to estimate the percentage of strains that a vaccine is likely to be effective against (known as 'vaccine strain coverage'). The genetic Meningococcal Antigen Typing System (gMATS) was developed to predict strain coverage by the four-component meningococcal serogroup B vaccine, 4CMenB, against large numbers of serogroup B strains. In this study, we analyzed 284 invasive meningococcal serogroup B isolates collected between 2010 and 2014 in Argentina. Genetic analyses showed that the vaccine antigens of the isolates were diverse and some genetic characteristics had not been found in isolates from other countries. However, vaccine strain coverage estimated by gMATS was consistent with that reported in other parts of the world and with strain coverage results obtained for a subset via another method, the human serum bactericidal antibody (hSBA) assay. These results highlight the need for continued monitoring of circulating bacterial strains to assess the estimated strain coverage of meningococcal serogroup B vaccines.

Bactericidal killing of meningococcal W strains isolated in Argentina by the sera of adolescents and infants immunized with 4-component meningococcal serogroup B vaccine (4CMenB).

Invasive meningococcal disease (IMD) is a life-threatening disease caused by meningococcal serogroups A, B, C, W, X, and Y, of which B and W are most common in Argentina. The 4-component meningococcal serogroup B (4CMenB) vaccine contains three purified recombinant protein antigens (Neisseria adhesin A [NadA], factor H binding protein [fHbp], and Neisserial Heparin Binding Antigen [NHBA]) and outer membrane vesicles (OMV), which is derived from the New Zealand epidemic strain and contains Porin A 1.4. These antigens are present and conserved in strains that belong to other serogroups. In this study, we show that 10/11 (91%) meningococcal serogroup W (MenW) strains selected to be representative of MenW isolates that caused IMD in Argentina during 2010-2011 were killed in bactericidal assays by the sera of adolescents and infants who had been immunized with the 4CMenB vaccine. We also show that MenW strains that caused IMD in Argentina during 2018-2021 were genetically similar to the earlier strains, indicating that the 4CMenB vaccine would likely still provide protection against current MenW strains. These data highlight the potential of 4CMenB vaccination to protect adolescents and infants against MenW strains that are endemic in Argentina.

Rubella vaccination of unknowingly pregnant women during mass campaigns for rubella and congenital rubella syndrome elimination, the Americas 2001-2008.

BACKGROUND: Due to the significant teratogenicity of rubella virus and the use of a live-attentuated vaccine, pregnancy is a contraindication of receipt of rubella vaccine (RCV). Data collected from several countries that have observed susceptible women who had received RCV during pregnancy documented that no infant with congenital rubella syndrome (CRS) has been born, so the risk is theoretical. As part of the regional initiative to eliminate rubella and CRS in the Americas, one of the key strategies was the vaccination of women of childbearing age. The implementation of mass vaccination campaigns targeting women of childbearing age in Argentina, Brazil, Costa Rica, Ecuador, El Salvador, and Paraguay provided an opportunity to further increase the body of knowledge on the safety of rubella vaccine if an unknowingly pregnant woman is vaccinated in early pregnancy. METHODS: Using a standard protocol, women who were unknowingly pregnant or become pregnant ≤ 30 days after receiving RCV were evaluated to determine immunity status (eg, susceptible, immune, and unknown) at the time of vaccination. Susceptible pregnant women were observed to determine the outcome of the pregnancy. For pregnancies that resulted in live births, serum samples were obtained from the newborn for rubella immunoglobulin (Ig) M antibody testing. If the newborn's serum sample was IgM positive, the infant was evaluated for manifestations of CRS. RESULTS: During the period 2001-2008, 48748253 women of childbearing age were vaccinated in the region of the Americas, 39542253 (81%) of whom were vaccinated in the 6 selected countries. Of these women, 30139 (0.07%) were pregnant or became pregnant ≤1 month after receiving vaccine and were followed up. On the basis of serological evaluation, 2894 (10%) women were classified as susceptible at the time of vaccination; of their pregnancies, 1980 (90%) resulted in a live birth. Sera from 70 (3.5%) of these infants were rubella IgM antibody positive, but none of the infants had features of CRS as a result of rubella vaccination. The maximum theoretical risk for CRS following rubella vaccination of susceptible pregnant women was 0.2%. Conclusions. The results of these studies from 6 select countries provides additional evidence showing an absence of risk of CRS associated with administering rubella vaccine shortly before or during pregnancy.

Effectiveness of mRNA-1273, BNT162b2, and BBIBP-CorV vaccines against infection and mortality in children in Argentina, during predominance of delta and omicron covid-19 variants: test negative, case-control study.

OBJECTIVE: To estimate the effectiveness of a two dose vaccine schedule (mRNA-1273, BNT162b2, and BBIBP-CorV) against SARS-CoV-2 infection and covid-19 related death and short term waning of immunity in children (3-11 years old) and adolescents (12-17 years old) during periods of delta and omicron variant predominance in Argentina. DESIGN: Test negative, case-control study. SETTING: Database of the National Surveillance System and the Nominalized Federal Vaccination Registry of Argentina. PARTICIPANTS: 844 460 children and adolescents without previous SARS-CoV-2 infection eligible to receive primary vaccination schedule who were tested for SARS-CoV-2 by polymerase chain reaction or rapid antigen test from September 2021 to April 2022. After matching with their corresponding controls, 139 321 (60.3%) of 231 181 cases remained for analysis. EXPOSURES: Two dose mRNA-1273, BNT162b2, and BBIBP-CorV vaccination schedule. MAIN OUTCOME MEASURES: SARS-CoV-2 infection and covid-19 related death. Conditional logistic regression was used to estimate the odds of SARS-CoV-2 infection among two dose vaccinated and unvaccinated participants. Vaccine effectiveness was estimated as (1-odds ratio)×100%. RESULTS: Estimated vaccine effectiveness against SARS-CoV-2 infection was 61.2% (95% confidence interval 56.4% to 65.5%) in children and 66.8% (63.9% to 69.5%) in adolescents during the delta dominant period and 15.9% (13.2% to 18.6%) and 26.0% (23.2% to 28.8%), respectively, when omicron was dominant. Vaccine effectiveness declined over time, especially during the omicron period, from 37.6% (34.2% to 40.8%) at 15-30 days after vaccination to 2.0% (1.8% to 5.6%) after ≥60 days in children and from 55.8% (52.4% to 59.0%) to 12.4% (8.6% to 16.1%) in adolescents.Vaccine effectiveness against death related to SARS-CoV-2 infection during omicron predominance was 66.9% (6.4% to 89.8%) in children and 97.6% (81.0% to 99.7%) in adolescents. CONCLUSIONS: Vaccine effectiveness in preventing mortality remained high in children and adolescents regardless of the circulating variant. Vaccine effectiveness in preventing SARS-CoV-2 infection in the short term after vaccination was lower during omicron predominance and decreasing sharply over time. TRIAL REGISTRATION: National Registry of Health Research IS003720.

Immunogenicity and reactogenicity of heterologous immunization against SARS CoV-2 using Sputnik V, ChAdOx1-S, BBIBP-CorV, Ad5-nCoV, and mRNA-1273.

Heterologous vaccination against coronavirus disease 2019 (COVID-19) provides a rational strategy to rapidly increase vaccination coverage in many regions of the world. Although data regarding messenger RNA (mRNA) and ChAdOx1 vaccine combinations are available, there is limited information about the combination of these platforms with other vaccines widely used in developing countries, such as BBIBP-CorV and Sputnik V. Here, we assess the immunogenicity and reactogenicity of 15 vaccine combinations in 1,314 participants. We evaluate immunoglobulin G (IgG) anti-spike response and virus neutralizing titers and observe that a number of heterologous vaccine combinations are equivalent or superior to homologous schemes. For all cohorts in this study, the highest antibody response is induced by mRNA-1273 as the second dose. No serious adverse events are detected in any of the schedules analyzed. Our observations provide rational support for the use of different vaccine combinations to achieve wide vaccine coverage in the shortest possible time.

Cost-effectiveness of introducing an MF59-adjuvanted trivalent influenza vaccine for older adults in Argentina.

INTRODUCTION: Influenza surveillance in Argentina reported influenza-like illness at a rate of 3500/100,000, a hospitalization rate of 15.5/100,000, and a death rate of 0.32/100,000 annually in adults aged over 65 years. The high burden of disease may be due to a combination of immunosenescence and the suboptimal clinical effectiveness of conventional, non-adjuvanted influenza vaccines in this age group. There is a clinical need for more effective influenza vaccines in this population. This study evaluated the cost-effectiveness of an MF59®-adjuvanted trivalent influenza vaccine (aTIV) in adults aged over 65 years in Argentina compared with the non-adjuvanted trivalent influenza vaccine (TIV) used under the current national vaccination policy. METHODS: A decision tree cost-effectiveness model was developed to estimate the cost-effectiveness of switching from TIV to aTIV in Argentinian older adults. The model compared cost and health benefits of vaccination in one influenza season from the payer perspective. The main predictions included survival, quality-adjusted survival, and costs. Model inputs were sourced from Argentina or internationally where local data was considered inaccurate. Vaccine efficacy assumptions were extracted from recently published, peer-reviewed scientific literature. RESULTS: Switching from TIV to aTIV would result in 170 deaths averted and 1310 incremental quality-adjusted life years (QALYs) gained. The incremental cost-effectiveness ratio per QALY was US $2660.59 from the payer perspective. In all sensitivity analyses, aTIV remained highly cost-effective. The probabilistic sensitivity analyses showed a 95% CI per QALY of US $113.74-7721.67. CONCLUSION: Introducing an adjuvanted influenza vaccine in Argentina is potentially beneficial and cost-effective relative to the currently-used TIV through the reduction of disease burden and utilization of healthcare resources.

[Incidence variation in malignancies associated or not with AIDS at an outpatient care center, 1997-2005]. / Variacion de la incidencia de tumores asociados o no al sida en un centro ambulatorio, 1997-2005.

In Argentina there are no published data on the incidence of AIDS (ARM) and non-AIDS related malignancies (non-ARM) in the HIV positive population. Our aim was to establish the incidence of these malignancies at an ambulatory care center between 1997 and 2005. We describe 103 cases of malignancies, 73 out of them were ARM and 30 were non-ARM. There were no differences in terms of age, gender and proportion of patients on highly active antiretroviral treatment (HAART). Among those patients with ARM, simultaneous diagnosis of malignancy and HIV infection was more frequently seen (p <0.001) and the proportion of patients with AIDS was higher (p = 0.015). Among those patients with non-ARM the mean duration of HIV infection and HAART was higher (p = 0.038 and 0.002 respectively); also was higher the mean CD4 count nadir (p = 0.009), and CD4 count at the time of malignancy diagnosis (p <0.001). The incidence of ARM was 18 cases/1000 patients-year in 1997 and dropped to 3.1 cases/1000 patients-year in 2005 (p = 0.001). The incidence of non-ARM was always lower than ARM, and similar in each year. In conclusion, ARM were more frequent than non-ARM, but their incidence dropped significantly because of massive use of HAART, while non-ARM remained stable. The high proportion of simultaneous diagnosis of ARM and HIV infection should enable much earlier HIV diagnosis.

Argentina's Successful Implementation Of A National Human Papillomavirus Vaccination Program.

Every year around fourteen million people globally are infected with human papillomavirus (HPV), the sexually transmitted virus that is the cause of most cervical cancers. A number of vaccines have been developed to protect against HPV, but in many countries, HPV vaccination rates have been low compared with rates for other recommended vaccines. Parental concerns, cost, and lack of information and awareness among both health professionals and parents are cited as important barriers to HPV vaccination. In Argentina the HPV vaccine has been provided to all eleven-year-old girls since 2011 as part of a comprehensive national program to prevent cervical cancer. Coverage increased from negligible levels before 2011 to a national average of 87.9 percent for the first dose, 71.6 percent for the second dose, and 52.2 percent for the third dose in 2013. There was a large variance in HPV vaccine coverage across the country's provinces. This article describes key strategies to overcome barriers to implementation of HPV vaccination and provides recommendations for policy makers.

Impact of a maternal immunization program against pertussis in a developing country.

BACKGROUND: Pertussis disease is a growing concern for developing countries. In Argentina, rates of illness and death peaked in 2011. More than 50% of fatalities due to pertussis occurred in infants younger than two months of age, too young for vaccination. In 2012, the government offered immunization with a vaccine containing Tdap to all pregnant women after 20weeks of gestation with the intent of reducing morbidity and mortality in young infants. METHODS: Maternal acellular pertussis vaccine impact on reducing infant disease burden was estimated based on data from the Argentinean Health Surveillance System. We divided Argentinean states in two groups experiencing high (>50) and low (⩽50) Tdap vaccine coverage and compared these two groups using a Bayesian structural time-series model. Low coverage regions were used as a control group, and the time series were compared before and after the implementation of the Tdap program. FINDINGS: We observed a relative reduction of 51% (95% CI [-67%, -35%]; p=0.001) in pertussis cases in high coverage states in comparison with the low coverage areas. Analysis of infants between two and six months showed a 44% (95% CI [-66%, -24%]; p=0.001) reduction in illness. Number of deaths was highest in 2011 with 76 fatalities, for an incidence rate of 2.9 per 100,000. Comparing with 2011, rates decreased by 87% to 10 subjects, or 0.9 per 100,000 in 2013. INTERPRETATION: We show an age-dependent protective effect of maternal Tdap immunization in a developing country for infants younger than six months.

Single-dose Universal Hepatitis A Immunization in One-year-old Children in Argentina: High Prevalence of Protective Antibodies up to 9 Years After Vaccination.

BACKGROUND: Single-dose hepatitis A virus (HAV) vaccination was implemented in all Argentinean children 12 months of age in 2005. Previous studies demonstrated high prevalence of protective antibody response 4 years after single-dose vaccination. This study assessed long-term seroprotection against HAV after vaccination. METHODS: Children who received 1 dose of HAV vaccine at 1 year of age at least 6 years before enrollment were included at 5 centers in Argentina between 2013 and 2014. Demographic and socioeconomic characteristics were collected through a questionnaire. Blood samples were tested for anti-HAV antibodies. Antibody values ≥10 mIU/mL were considered seroprotective. Logistic regression analysis was performed to evaluate the association between demographic and socioeconomic variables and seroprotection. RESULTS: A total of 1088 children were included, with a median postvaccination interval of 7.7 years (range 6.3-9.2 years). Of these children, 97.4% (95% confidence interval: 96.3%-98.3%) had protective antibodies against HAV. No association between demographic or socioeconomic variables and seroprotection was found. Geometric mean concentration of antibody levels against HAV was 170.5 mUI/mL (95% confidence interval: 163.2-178.2 mUI/mL). CONCLUSIONS: Single-dose universal hepatitis A immunization in 1-year-old children resulted in sustained immunologic protection for up to 9 years in Argentina. These findings, along with the low current disease burden, confirm the success of the intervention.

Cost-effectiveness analysis of rotavirus vaccination in Argentina.

BACKGROUND: Rotavirus is a leading cause of severe diarrhea in children under 5. In Argentina, the most affected regions are the Northeast and Northwest, where hospitalizations and deaths are more frequent. This study estimated the cost-effectiveness of adding either of the two licensed rotavirus vaccines to the routine immunization schedule. METHODS: The integrated TRIVAC vaccine cost-effectiveness model from the Pan American Health Organization's ProVac Initiative (Version 2.0) was used to assess health benefits, costs savings, life-years gained (LYGs), DALYs averted, and cost/DALY averted of vaccinating 10 successive cohorts, from the health care system and societal perspectives. Two doses of monovalent (RV1) rotavirus vaccine and three doses of pentavalent (RV5) rotavirus vaccine were each compared to a scenario assuming no vaccination. The price/dose was US$ 7.50 and US$ 5.15 for RV1 and RV5, respectively. We ran both a national and sub-national analysis, discounting all costs and benefits 3% annually. Our base case results were compared to a range of alternative univariate and multivariate scenarios. RESULTS: The number of LYGs was 5962 and 6440 for RV1 and RV5, respectively. The cost/DALY averted when compared to no vaccination from the health care system and societal perspective was: US$ 3870 and US$ 1802 for RV1, and US$ 2414 and US$ 358 for RV5, respectively. Equivalent figures for the Northeast were US$ 1470 and US$ 636 for RV1, and US$ 913 and US$ 80 for RV5. Therefore, rotavirus vaccination was more cost-effective in the Northeast compared to the whole country; and, in the Northwest, health service's costs saved outweighed the cost of introducing the vaccine. Vaccination with either vaccine compared to no vaccination was highly cost-effective based on WHO guidelines and Argentina's 2011 per capita GDP of US$ 9090. Key variables influencing results were vaccine efficacy, annual loss of efficacy, relative coverage of deaths, vaccine price, and discount rate. CONCLUSION: Compared to no vaccination, routine vaccination against rotavirus in Argentina would be highly cost-effective with either vaccine. Health and economic benefits would be higher in the Northeast and Northwest regions, where the intervention would even be cost-saving.