COVID-19 Vaccines: Current Understanding on Immunogenicity, Safety, and Further Considerations.

The world has entered the second wave of the COVID-19 pandemic, and its intensity is significantly higher than that of the first wave of early 2020. Many countries or regions have been forced to start the second round of lockdowns. To respond rapidly to this global pandemic, dozens of COVID-19 vaccine candidates have been developed and many are undergoing clinical testing. Evaluating and defining effective vaccine candidates for human use is crucial for prioritizing vaccination programs against COVID-19. In this review, we have summarized and analyzed the efficacy, immunogenicity and safety data from clinical reports on different COVID-19 vaccines. We discuss the various guidelines laid out for the development of vaccines and the importance of biological standards for comparing the performance of vaccines. Lastly, we highlight the key remaining challenges, possible strategies for addressing them and the expected improvements in the next generation of COVID-19 vaccines.

Vaccines and routine immunization strategies during the COVID-19 pandemic.

Severe acute respiratory syndrome coronavirus 2 related disease (COVID-19) is now responsible for one of the most challenging and concerning pandemics. By August 2020, there were almost 20 million confirmed cases worldwide and well over half-million deaths. Since there is still no effective treatment or vaccine, non-pharmaceutical interventions have been implemented in an attempt to contain the spread of the virus. During times of quarantine, immunization practices in all age groups, especially routine childhood vaccines, have also been interrupted, delayed, re-organized, or completely suspended. Numerous high-income as well as low- and middle-income countries are now experiencing a rapid decline in childhood immunization coverage rates. We will, inevitably, see serious consequences related to suboptimal control of vaccine-preventable diseases (VPDs) in children concurrent with or following the pandemic. Routine pediatric immunizations of individual children at clinics, mass vaccination campaigns, and surveillance for VPDs must continue as much as possible during pandemic.

Programa nacional de inmunizacion en Chile: pasado, presente y futuro / National immunization program in Chile: past, present and future

El Programa Ampliado de Inmunizaciones (PAI) a nivel mundial nace en 1974 como iniciativa de la Organización Mundial de la Salud (OMS) y la Organización Panamericana de la Salud (OPS). En Chile, el actual Programa Nacional de Inmunizaciones (PNI) se origina en el Plan Ampliado de Inmunizaciones (PAI) establecido en el año 1978. En sus inicios, el PAI se basó en disposiciones legales definidas en 1975, que establecía las Enfermedades Trasmisibles de Vacunación Obligatoria. Desde el año 2010, el Decreto Exento N°6 promulgado el 29 de enero, se dispone la vacunación obligatoria contra enfermedades inmunoprevenibles de la población del país. Posteriormente se han realizado modificaciones al decreto exento N°6 reflejando la incorporación de nuevas vacunas al calendario, modificaciones en los grupos objetivo y/o cambios en las estrategias de vacunación, entre otros. En estas disposiciones también se establece que el Ministerio de Salud debe asegurar el acceso gratuito a vacunaciones seguras y efectivas para toda la población objetivo. El objetivo del artículo, es describir la evolución de las iniciativas de vacunación en nuestro país, desde antes de la creación del PAI, la sistematización de las estrategias de vacunación una vez que se establece el programa hasta las modificaciones realizadas en la última década.

The Expanded Program on Immunization (EPI) worldwide was created in 1974 as an initiative of the World Health Organization (WHO) and the Pan American Health Organization (PAHO). In Chile, the current National Immunization Program (PNI) originates from the Extended Inmunization Plan (EPI) established in 1978. In its beginnings, the EPI was based on legal provisions defined in 1975, which established the Communicable Diseases of Compulsory Vaccination. Since 2010, the Exempt Decree No. 6 promulgated on January 29, provides the Mandatory Vaccination against Immune preventable Diseases of the Population of the Country. Subsequently there have been modifications to the Exempt Decree No. 6 reflecting the incorporation of new vaccines to the calendar, modifications in the target groups and /or changes in vaccination strategies, among others. These provisions also state that the Ministry of Health must ensure free access to safe and effective vaccinations for the entire target population. The aim oh this article is to describe evolution of vaccination initiatives in our country, from before the creation of the EPI, the systematization of vaccination strategies once the program is established, until the modifications made in the last decade.

Priorización de nuevas vacunas e innovación al servicio de estrategias de vacunación / New vaccines prioritization and immunization-related innovation

La vacunación es el medio más efectivo para controlar la morbilidad y mortalidad relacionadas con enfermedades infecciosas. Para lograr esto, necesitamos vacunas inmunogénicas y seguras que faciliten y mejoren sus condiciones de transporte, almacenamiento y administración. Gracias a los avances en inmunología y bioinformática, es posible impulsar el descubrimiento de nuevas vacunas para enfrentar la tuberculosis, el virus respiratorio sincicial, el Streptococcus agalactiae, la enfermedad meningocócica invasora, entre otros. Así también, nuevas tecnologías, como la producción de vacunas utilizando plantas transgénicas y parches de microagujas, los cuales podrían facilitar la producción, disminuir los costos y efectos adversos. Sin embargo, no solo necesitamos las vacunas, sino que debemos conocer la epidemiología de las enfermedades prevenibles con vacuna para tomar decisiones fundadas, con el objetivo de planificar estrategias sanitarias, medir su impacto y evaluar la seguridad de su utilización, para alcanzar las metas de salud pública y la confianza de la población.

Vaccination is the most effective strategy to avoid morbidity and mortality related to infectious diseases. To achieve this, we need immunogenic and safe vaccines that facilitate and improve its transport, storage and administration conditions. Thanks to current advances in immunology and bioinformatics, it is possible to boost the discovery of new vaccines to deal with tuberculosis, the respiratory syncytial virus, Streptococcus agalactiae, meningococcal invasive disease, among others. In addition to new technologies such as the production of plant-based vaccines, and microneedles patches, which can facilitate its production, reducing costs and adverse effects. However, vaccines is not the only thing that we need, because we must know the epidemiology and burden of disease to take informed decisions to design optimal strategies, measuring their impact and assessing the safety of their use in order to achieve the goals health and population confidence.

Global Perspectives on Immunization During Pregnancy and Priorities for Future Research and Development: An International Consensus Statement.

Immunization during pregnancy has been recommended in an increasing number of countries. The aim of this strategy is to protect pregnant women and infants from severe infectious disease, morbidity and mortality and is currently limited to tetanus, inactivated influenza, and pertussis-containing vaccines. There have been recent advancements in the development of vaccines designed primarily for use in pregnant women (respiratory syncytial virus and group B Streptococcus vaccines). Although there is increasing evidence to support vaccination in pregnancy, important gaps in knowledge still exist and need to be addressed by future studies. This collaborative consensus paper provides a review of the current literature on immunization during pregnancy and highlights the gaps in knowledge and a consensus of priorities for future research initiatives, in order to optimize protection for both the mother and the infant.

Effect of State Immunization Information System Centralized Reminder and Recall on HPV Vaccination Rates.

BACKGROUND: Although autodialer centralized reminder and recall (C-R/R) from state immunization information systems (IISs) has been shown to raise childhood vaccination rates, its impact on human papillomavirus (HPV) vaccination rates is unclear. METHODS: In a 4-arm pragmatic randomized controlled trial across 2 states, we randomly selected practices representative of the specialty (pediatrics, family medicine, and health center) where children received care. Within each practice, patients 11 to 17.9 years old who had not completed their HPV vaccine series (NY: N = 30 616 in 123 practices; CO: N = 31 502 in 80 practices) were randomly assigned to receive 0, 1, 2, or 3 IIS C-R/R autodialer messages per vaccine dose. We assessed HPV vaccine receipt via the IIS, calculated intervention costs, and compared HPV vaccine series initiation and completion rates across study arms. RESULTS: In New York, HPV vaccine initiation rates ranged from 37.0% to 37.4%, and completion rates were between 29.1% and 30.1%, with no significant differences across study arms. In Colorado, HPV vaccine initiation rates ranged from 31.2% to 33.5% and were slightly higher for 1 reminder compared with none, but vaccine completion rates, ranging from 27.0% to 27.8%, were similar. On adjusted analyses in Colorado, vaccine initiation rates were slightly higher for 1 and 3 C-R/R messages (adjusted risk ratios 1.07 and 1.04, respectively); completion rates were slightly higher for 1 and 3 C-R/R messages (adjusted risk ratios 1.02 and 1.03, respectively). CONCLUSIONS: IIS-based C-R/R for HPV vaccination did not improve HPV vaccination rates in New York and increased vaccination rates slightly in Colorado.

Disease burden and seasonal impact of improving rotavirus vaccine coverage in the United States: A modeling study.

BACKGROUND: Prior to vaccine introduction in 2006, rotavirus was the leading cause of severe diarrhea in children under five years of age in the U.S. Vaccination of infants has led to major reductions in disease burden, a shift in the seasonal peak and the emergence of a biennial pattern of disease. However, rotavirus vaccine coverage has remained relatively low (70-75%) compared to other infant immunizations in the U.S. Part of the reason for this lower coverage is that children whose care is provided by family practitioners (FP) have considerably lower probability of being vaccinated compared to those seen be pediatricians (PE). We used a dynamic transmission model to assess the impact of improving rotavirus vaccine coverage by FP and/or PE on rotavirus gastroenteritis (RVGE) incidence and seasonal patterns. METHODS: A deterministic age-structured dynamic model with susceptible, infectious, and recovered compartments (SIRS model) was used to simulate rotavirus transmission and vaccination. We estimated the reduction of RVGE cases by 2 doses of rotavirus vaccine with three vaccination scenarios: (Status Quo: 85% coverage by pediatricians and 45% coverage by family practitioners; Improved FP: 85% coverage by pediatricians and family practitioners; Improved FP+PE: 95% coverage by pediatricians and family practitioners). In addition, we tested the sensitivity of the model to the assumption of random mixing patterns between children visiting pediatricians and children visiting family practitioners. RESULTS: In this model, higher vaccine coverage provided by family practitioners and pediatricians leads to lower incidence of severe RVGE cases (23% averted in Improved FP and 57% averted in Improved FP+PE compared to Status Quo) including indirect effects. One critical impact of higher total vaccine coverage is the effect on rotavirus epidemic patterns in the U.S.; the biennial rotavirus epidemic patterns shifted to reduced annual epidemic patterns. Additionally, assortative mixing patterns in children visiting pediatricians and family practitioners amplify the impact of increasing vaccine coverage. CONCLUSION: Other high-income countries that introduced vaccine have not experienced biennial patterns, like the U.S. Our results suggest that increasing overall vaccine coverage to 85% among infants would lead to an overall reduction in incidence with annual epidemic patterns.

Effectiveness of email-based reminders to increase vaccine uptake: a systematic review.

BACKGROUND: In times of vaccine hesitancy and decreasing immunization coverage, it is crucial to exploit the potential of digital solutions to support immunization programmes and ultimately increase vaccine uptake. Scant evidence exists on the impact of email-based immunization reminders. In particular, while email communication is exponentially increasing at the global level, its use for health communication is still sporadic and limited data exists on its application to immunization programmes. The objective of this study is to systematically retrieve and critically appraise the available literature on the effectiveness of email-based reminders to increase vaccine uptake, with the ultimate aim to inform and encourage its integration in the implementation of immunization programmes. METHODS: We conducted a systematic review of literature following the PRISMA. We included studies providing quantitative comparative data on any measure of vaccine uptake. We extracted data on study design, study population, vaccine type and details of email-based interventions; data were pooled by type of comparison (no reminders, traditional reminders, other digital reminders). RESULTS: Eleven studies were included, 90% with experimental study designs. While email communication succeeds in increasing vaccine uptake when compared with no intervention, weak and heterogeneous data exist supporting the superiority of email reminders, as compared to traditional methods or other digital reminders. Encouraging evidence report the effectiveness of reminder methods combining different strategies and tailored to target populations' preferences. CONCLUSIONS: Theoretically, email communication offers many advantages: it is cheaper and faster, it can be automated and linked to electronic immunization registries, and reach people on the move. As we urge the need for further research to prove email communication impact on vaccine uptake in different settings, we underline the importance of identifying how to best integrate email communication in vaccine delivery equipping immunization programmes with technical infrastructures and normative frameworks suitable to embrace innovation.

Immunological mechanisms of inducing HIV immunity in infants.

The potential advantages and unique challenges of the early life immune system for the development of HIV-specific broadly neutralizing antibodies were discussed during a workshop entitled "Immunological Mechanisms of Inducing HIV Immunity in Infants" sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH) in conjunction with the 2018 HIVR4P Conference held in Madrid, Spain. A safe and effective HIV vaccine remains a critical need in the fight against the HIV pandemic, especially to prevent emerging infections in infants, adolescents, and young adults. To successfully target these populations, a vaccine should ideally induce protective immune responses during childhood. Interestingly, several recent studies highlighting differences in immune responses between adults and children have suggested that the early life immune system could present advantages for the elicitation of broadly neutralizing antibodies (bnAbs), a response highly desired for an HIV vaccine. Notably, HIV-infected children develop bnAbs responses earlier and more frequently than infected adults; with emerging evidence that the pathways of elicitation of bnAb lineages may differ between adults and children. Moreover, there is precedent for the prevention of lifelong infections with pediatric immunization, and early life provides a unique window of opportunity for the administration of a multi-dose HIV vaccine that will likely be needed to achieve protective immunity. Further understanding of how the distinct early life immune system can be harnessed to trigger bnAb lineages for induction of durable and polyfunctional HIV-specific immunity is warranted. This strategy will include testing promising HIV vaccine candidates in pediatric populations in preclinical and clinical studies. Novel approaches to identify molecular markers of protection are also key to guide and accelerate pediatric HIV vaccine development.

Factors influencing rates of human papillomavirus vaccination.

PURPOSE: Failure modes and effects analysis (FMEA) was used to identify ways in which community clinic practices related to suboptimal human papillomavirus (HPV) vaccination rates could be improved. METHOD: FMEA is a standardized safety method that helps determine where processes fail, the impact of failures, and needed process changes. In a quality improvement initiative conducted at an academic health center-based community clinic, a multidisciplinary team used FMEA to map HPV vaccination processes and identify areas for improvement of vaccination practices. Risk priority numbers (RPNs) were assigned to identified failure modes based on likelihood of occurrence, likelihood of detection, and ability to correct locally. Failure modes with the highest RPNs were targeted for process improvements. RESULTS: High RPN failure modes were related to clinic processes for follow-up, immunization status checks during well-child visits, and vaccination discussions during sick-child visits. New procedures included scheduling follow-up vaccinations and reminders during the initial vaccination appointment. HPV immunization rates improved following implementation of these procedures, indicating that clinic processes focused on patient follow-up can impact vaccination series completion. CONCLUSION: FMEA processes can help health systems identify workflow barriers and locally relevant opportunities for improvement. Team-based approaches to care process improvements can also benefit from standardized problem identification and solving.

Antibody-based therapies for Huntington's disease: current status and future directions.

The types of treatments and interventions being developed for chronic neurodegenerative disorders have expanded considerably in recent years. In addition to the variety of targets being pursued, strategies have moved from symptom management to more directed disease-modifying approaches. Among them are antibody-based therapies, which are not only being evaluated for a range of tauopathies and synucleinopathies, but are also emerging as a potential application for monogenic disorders of the central nervous system (CNS), including Huntington's disease (HD). Despite the excitement around the early trial data of anti-sense oligonucleotides (ASO) treatment for such disorders, antibody therapies may hold the key to tackling another aspect of the disease that could be critical to its pathogenesis. While gene-based methodologies are designed to lower, predominantly within cellular elements, mutant huntingtin protein (mHtt) - the genetic product of HD - the pathological protein is abundant in free forms and in several compartments including the cerebrospinal fluid, the plasma and the extracellular matrix. With accumulating evidence for the spreading and seeding capacities of mHtt, it may indeed be essential to target the protein both intracellularly and extracellularly. Therefore, free forms of mHtt not only represents an ideal target for antibodies, but one that needs to be addressed if meaningful and maximal clinical benefits are to be expected. This review explores the potential use of antibody-based therapies to treat HD, including the rationale for this approach as well as the pre-clinical data supporting it. The potential challenges that will need to be considered if such route is to be pursued clinically are also discussed.

New Pertussis Vaccines: A Need and a Challenge.

Effective diphtheria, tetanus toxoids, whole-cell pertussis (wP) vaccines were used for massive immunization in the 1950s. The broad use of these vaccines significantly reduced the morbidity and mortality associated with pertussis. Because of reports on the induction of adverse reactions, less-reactogenic acellular vaccines (aP) were later developed and in many countries, especially the industrialized ones, the use of wP was changed to aP. For many years, the situation of pertussis seemed to be controlled with the use of these vaccines, however in the last decades the number of pertussis cases increased in several countries. The loss of the immunity conferred by the vaccines, which is faster in the individuals vaccinated with the acellular vaccines, and the evolution of the pathogen towards geno/phenotypes that escape more easily the immunity conferred by the vaccines were proposed as the main causes of the disease resurgence. According to their composition of few immunogens, the aP vaccines seem to be exerting a greater selection pressure on the circulating bacterial population causing the prevalence of bacterial isolates defective in the expression of vaccine antigens. Under this context, it is clear that new vaccines against pertussis should be developed. Several vaccine candidates are in preclinical development and few others have recently completed phaseI/phaseII trials. Vaccine candidate based on OMVs is a promising candidate since appeared overcoming the major weaknesses of current aP-vaccines. The most advanced development is the live attenuated-vaccine BPZE1 which has successfully completed a first-in-man clinical trial.

Prevention of Food Allergy: The Significance of Early Introduction.

Over the last two decades, the prevalence of food allergies has registered a significant increase in Westernized societies, potentially due to changes in environmental exposure and lifestyle. The pathogenesis of food allergies is complex and includes genetic, epigenetic and environmental factors. New evidence has highlighted the role of the intestinal microbiome in the maintenance of the immune tolerance to foods and the potential pathogenic role of early percutaneous exposure to allergens. The recent increase in food allergy rates has led to a reconsideration of prevention strategies for atopic diseases, mainly targeting the timing of the introduction of solid foods into infants' diet. Early recommendation for high atopy risk infants to delay the introduction of potential food allergens, such as cow's milk, egg, and peanut, until after the first year of life, has been rescinded, as emerging evidence has shown that these approaches are not effective in preventing food allergies. More recently, high-quality clinical trials have suggested an opposite approach, which promotes early introduction of potential food allergens into infants' diet as a means to prevent food allergies. This evidence has led to the production of new guidelines recommending early introduction of peanut as a preventive strategy for peanut allergy. However, clinical trials investigating whether this preventive dietary approach could also apply to other types of food allergens have reported ambiguous results. This review focuses on the latest high-quality evidence from randomized controlled clinical trials examining the timing of solid food introduction as a strategy to prevent food allergies and also discusses the possible implications of early complementary feeding on both the benefits and the total duration of breastfeeding.

Immunization Education in US Pharmacy Colleges and Schools.

Objective. To determine the extent to which immunization is covered at US colleges and schools of pharmacy and to characterize what immunization- and vaccine-related content is taught. Methods. An invitation to complete a 23-question online survey instrument was sent to 128 accredited US pharmacy colleges and schools. Frequency and descriptive statistics were used to characterize the data, and the Fisher exact test was used to compare opportunities for students to engage in introductory and advanced pharmacy practice experiences (IPPEs and APPEs) at schools located in states that did or did not allow pharmacy students and interns to vaccinate. Results. Eighty accredited US pharmacy schools responded to the survey (62.5% response rate). The APhA Pharmacy-Based Immunization Delivery Program was offered by 73 (91.3%) schools, while a different immunization certificate program was offered by 5 (6.3%) schools. Sixty-nine (86.3%) and 36 (45%) of the schools had integrated immunization topics into their required core curriculum (mean 8.4 contact hours) and elective curriculum, respectively. Of the 27 immunization-related topics identified, 23 (85.2%) were covered by at least 80% of schools. More than 80% of schools offered IPPEs and more than 90% offered APPEs that provided opportunities for students to engage in immunization-related activities. Schools located in states that permitted pharmacy students and interns to vaccinate more commonly offered immunization-related opportunities through IPPEs (86.5% vs. 0%) and APPEs (97.3% vs. 20%) than those schools in states that did not. Conclusion. Immunization curricula at US colleges and schools of pharmacy appear to align with ACPE standards, as well as the recommendations of the American Association of Colleges of Pharmacy and the American College of Clinical Pharmacy. Furthermore, nearly all of the schools are using the APhA Program to do so.

Elimination of Nonmedical Immunization Exemptions in California and School-Entry Vaccine Status.

BACKGROUND AND OBJECTIVES: California implemented Senate Bill 277 (SB277) in 2016, becoming the first state in nearly 30 years to eliminate nonmedical exemptions from immunization requirements for schoolchildren. Our objectives were to determine (1) the impacts of SB277 on the percentage of kindergarteners entering school not up-to-date on vaccinations and (2) if geographic patterns of vaccine refusal persisted after the implementation of the new law. METHODS: At the state level, we analyzed the magnitude and composition of the population of kindergarteners not up-to-date on vaccinations before and after the implementation of SB277. We assessed correlations between previous geographic patterns of nonmedical exemptions and patterns of the remaining entry mechanisms for kindergarteners not up-to-date after the law's implementation. RESULTS: In the first year after SB277 was implemented, the percentage of kindergartners entering school not up-to-date on vaccinations decreased from 7.15% to 4.42%. The conditional entrance rate fell from 4.43% to 1.91%, accounting for much of this decrease. Other entry mechanisms for students not up-to-date, including medical exemptions and exemptions for independent study or homeschooled students, largely replaced the decrease in the personal belief exemption rate from 2.37% to 0.56%. In the second year, the percentage of kindergartners not up-to-date increased by 0.45%, despite additional reductions in conditional entrants and personal belief exemptions. The correlational analysis revealed that previous geographic patterns of vaccine refusal persisted after the law's implementation. CONCLUSIONS: Although the percentage of incoming kindergarteners up-to-date on vaccinations in California increased after the implementation of SB277, we found evidence for a replacement effect.

Missed Opportunities for Rotavirus Vaccination.

BACKGROUND: Rotavirus remains an important cause of gastroenteritis and has been associated with the hospitalization of 34 to 53 per 10 000 children <5 years of age in the United States annually from 2008 to 2012. Rotavirus vaccines are underused compared with other routine vaccines. We describe rotavirus vaccine coverage and missed opportunities for rotavirus vaccination. METHODS: The National Immunization Survey is a random-digit-dial, population-based survey including US children 19 to 35 months of age. Children fully vaccinated for rotavirus were those who received 3 doses of the pentavalent rotavirus vaccine, 2 doses of the monovalent rotavirus vaccine, or ≥3 doses of either vaccine type. Doses of the diphtheria-tetanus-acellular pertussis vaccine received from 6 weeks through 8 months and 0 days of age when the rotavirus vaccine was not received were considered missed opportunities for rotavirus vaccination according to Advisory Committee on Immunization Practices (ACIP) guidelines, and doses of the diphtheria-tetanus-acellular pertussis vaccine or measles-mumps-rubella vaccine from 6 weeks through 24 months and 0 days of age were considered missed opportunities according to World Health Organization recommendations. RESULTS: Of the 14 571 children included in the 2014 National Immunization Survey, 71% were fully vaccinated for rotavirus. Lower socioeconomic status increased the likelihood of being unvaccinated for rotavirus. Among the 14% of children who received no doses of the rotavirus vaccine, 72% had ≥1 ACIP-defined missed opportunities, and 83% had ≥1 World Health Organization-defined missed opportunities. Higher socioeconomic status increased the likelihood of having missed opportunities. Complete rotavirus vaccine coverage could be improved to 81% if all missed opportunities within the ACIP-recommended schedule were addressed. CONCLUSIONS: Addressing missed opportunities for rotavirus vaccination is essential to achieving the 80% rotavirus vaccine coverage target outlined by Healthy People 2020.

Immunizations and vaccines: a decade of successes and reversals, and a call for 'vaccine diplomacy'.

Over the last decade we have seen extraordinary public health gains due to expansions in global vaccination programs led by United Nations (UN) agencies, including Gavi, the Vaccine Alliance, UNICEF and the WHO. These initiatives have reduced childhood deaths from measles, tetanus and other vaccine-preventable diseases by almost one half. There is additional excitement over the potential development and introduction of new vaccines to prevent highly lethal respiratory virus infections, as well as tuberculosis, malaria, HIV/AIDS and several neglected tropical diseases. However, these successes are under threat due to political instability, conflict and an accelerating antivaccine movement. New initiatives in vaccine diplomacy will be required to combat these challenges.