Interchangeability of different COVID-19 vaccine platforms as booster doses: A phase 3 study mimicking real-world practice.

BACKGROUND: The COVID-19 pandemic is over but the highly immunized or naturally exposed global population still requires booster vaccinations against newly emerging SARS-CoV-2 variants. We assessed safety and immunogenicity of booster doses of COVID-19 vaccines based on three different platforms in a setting that mimics the current routine practice in Brazil. METHODS: In this phase 3 study from 14 February 2023 to 12 June 2023 we enrolled previously immunized adults to receive an additional booster dose of one of three vaccines. Immunogenicity against ancestor SARS-CoV-2 and Omicron BF.7, BQ.1.1.3, and XBB.1.5.6 sub-lineages was measured as ELISA IgG or virus neutralizing (VNT) antibodies and safety/reactogenicity assessed using diary cards. RESULTS: Volunteers with a history of full primary COVID-19 immunization striated to three cohorts according to their previous booster vaccination history-0 (n = 26), 1 (n = 140) or 2 (n = 606) booster vaccinations-were randomized 2:1:1 to receive either recombinant protein (SCB-2019, Clover), adenovirus-vector (ChAdOx1-S, AstraZeneca/Fiocruz), or mRNA (BNT162b2, Pfizer/Wyeth). Baseline antibody titers were higher in individuals who had received one or two boosters and titers against both ancestor and Omicron sub-lineages increased in all groups regardless of the number of previous booster doses or the vaccine used. Day 28 geometric mean titers (GMTs) and geometric mean-fold rises (GMFR) against all variants were higher after BNT162b than SCB-2019 or ChAdOx1-S, but BNT162b groups displayed more rapid antibody waning at Day 84. Within cohorts each vaccine elicited similar GMFR against the different SARS-CoV-2 strains. All vaccines were well tolerated with similar solicited reactogenicity profiles. CONCLUSIONS: Protein, adenovirus-vector or mRNA vaccine boosters were equally well tolerated and immunogenic against ancestor SARS-CoV-2 and Omicron sub-lineages in fully primed adults with 0-2 prior boosters. BNT162b induced the highest immune responses but also the most rapid waning of antibodies 3 months after vaccination. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT05812586.

Clinical trial capacity building in a pandemic-outcome of a rapid site readiness project in Latin America.

Background: Latin America (Latam) has a tradition of large-scale vaccine trials. Because of fluctuating demand, many sites have downsized their infrastructure. Therefore, BMGF launched a clinical trial site-readiness initiative early in the coronavirus-2019 (COVID-19) pandemic including Latam countries between August and September 2020. This survey evaluated clinical development performance measures pre/post initiative (September 2022). Results: 20/21 prequalified sites participated in COVID-19 vaccine/drug development trials. 156 clinical trials (140 COVID-19 vaccine/drug trials) were initiated in the 2 years since prequalification, compared to 176 in the 5 years before. 33,428/37,810 participants were included in COVID-19 programs. The number of enrolled subjects/day across sites quadrupled from 15 (1-35) to 63 (5-300). The dropout rate was 6.8%. Study approval timelines were reduced from 60 (12-120) to 35 (5-90) days. Mean qualified staff was increased from 24 (6-80) to 88 (22-180). Conclusion: Clinical trial sites across Latam were successfully prequalified to participate in COVID-19 developments. For the 100 days mission of vaccine availability in a new pandemic sufficient and well-trained clinical trial sites readily available are essential. This is only achievable if sites-especially in low/middle-income countries-are maintained active through a constant flow of vaccine studies.

Assessment of health care workers preparedness to epidemics: A case of Ebola virus disease preparedness in private hospitals in Kampala, Uganda.

INTRODUCTION: Unrecognized Ebola Virus Disease (EVD) can lead to multiple chains of transmissions if the first caretakers are not trained and prepared. This study aimed to assess healthcare workers (HCWs) preparedness in private hospitals located in Kampala, to detect, respond and prevent EVD. METHODOLOGY: A descriptive cross-sectional study was carried out among HCWs in direct clinical care provision in four private hospitals, and in one Ebola Treatment Unit (ETU) using a self-administered questionnaire from March to June 2020. RESULTS: 222 HCWs agreed to participate aged from 19 to 64 years and with 6 months to 38 years of practice where most were nurses (44%). 3/5 hospitals did not have written protocols on EVD case management, and only one (ETU) had an exclusive emergency team. 59% were not sure whether contact tracing was taking place. Private hospitals were not included in EVD trainings organized by the Ministry of Health (MoH). In addition, HCWs in private hospitals were not empowered by the MoH to take part in EVD case management. Despite these shortcomings, only 66% of HCWs showed an interest to be immunized. Knowledge about potential Ebola vaccines was generally poor. CONCLUSIONS: In Kampala, Uganda, establishment of a more comprehensive preparedness and response strategy for EVD outbreaks is imperative for HCWs in private facilities, including a wide vaccination educational program on Ebola vaccination. The findings from this study if addressed will likely improve the preparedness and management of future Ebola outbreaks in Uganda.

Novel Oral Polio Vaccine Type 2 Use for Polio Outbreak Response: A Global Effort for a Global Health Emergency.

A sharp rise in circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks in the years following the cessation of routine use of poliovirus type 2-containing oral polio vaccine and the trend of seeding new emergences with suboptimal vaccination response during the same time-period led to the accelerated development of the novel oral polio vaccine type 2 (nOPV2), a vaccine with enhanced genetic stability and lower likelihood of reversion to neuroparalytic variants compared to its Sabin counterpart. In November 2020, nOPV2 became the first vaccine to be granted an Emergency Use Listing (EUL) by the World Health Organization (WHO) Prequalification Team (PQT), allowing close to a billion doses to be used by countries within three years after its first rollout and leading to full licensure and WHO prequalification (PQ) in December 2023. The nOPV2 development process exemplifies how scientific advances and innovative tools can be applied to combat global health emergencies in an urgent and adaptive way, building on a collaborative effort among scientific, regulatory and implementation partners and policymakers across the globe.

Landscaping analysis of immunization progress and program structures in selected middle income Southeast Asian countries.

This study examined the performance and structures of national immunization program in five middle-income Southeast Asian countries - Malaysia, Thailand, Philippines, Viet Nam, and Myanmar, and analyzed how the different structures relate to the difference in program performance to identify effective strategies in the study countries that facilitated good immunization performance. Data were derived from published literature, and WHO/UNICEF/Gavi databases, with 2010 as the baseline year. UMICs Malaysia and Thailand maintained ≥90 % coverage from 2010 to 2020 and even during the COVID-19 pandemic in 2021. LMICs Viet Nam and donor-supported Myanmar also achieved 80-90 % coverage for most routine vaccines in 2020. The Philippines have not reached ≥90 % coverage since 2010, with the maximum only 72 % (MCV1 and Polio3) in 2020. All study countries prioritize immunization and increased government financing since 2010 by minimum 91 % in Malaysia and 1897 % in Myanmar. However, Myanmar still largely depended on donor support with government financing only 32 % of immunization costs in 2021. The Philippines funds 100 % of immunization costs and ensures sustainable financing for the NIP through earmarked "sin tax" revenues from alcohol and tobacco. Donor support influenced new vaccine introductions among the study countries, with Gavi countries Myanmar and Viet Nam introducing more new vaccines, compared to Gavi-ineligible Malaysia and Thailand. The Philippines reported vaccine stock-outs every year amounting to 28 stock-outs events from 2010 to 2019, compared to only 1-4 stockouts in the other study countries. Donor support, innovative financing, and domestic vaccine manufacturing all play an important role in the efficient delivery of immunization services as demonstrated by the several new vaccine introductions and high immunization rates in Myanmar though Gavi and UNICEF support, additional annual $1.2 billion budget for health and immunization from "sin taxes" in the Philippines, and lack of stockouts for vaccines sourced at affordable prices from domestic manufacturers in Viet Nam.

Boosting with adjuvanted SCB-2019 elicits superior Fcγ-receptor engagement driven by IgG3 to SARS-CoV-2 spike.

With the continued emergence of variants of concern, the global threat of COVID-19 persists, particularly in low- and middle-income countries with limited vaccine access. Protein-based vaccines, such as SCB-2019, can be produced on a large scale at a low cost while antigen design and adjuvant use can modulate efficacy and safety. While effective humoral immunity against SARS-CoV-2 variants has been shown to depend on both neutralization and Fc-mediated immunity, data on the effectiveness of protein-based vaccines with enhanced Fc-mediated immunity is limited. Here, we assess the humoral profile, including antibody isotypes, subclasses, and Fc receptor binding generated by a boosting with a recombinant trimer-tag protein vaccine SCB-2019. Individuals who were primed with 2 doses of the ChAdOx1 vaccine were equally divided into 4 groups and boosted with following formulations: Group 1: 9 µg SCB-2019 and Alhydrogel; Group 2: 9 µg SCB-2019, CpG 1018, and Alhydrogel; Group 3: 30 µg SCB-2019, CpG 1018, and Alhydrogel; Group 4: ChAdOx1. Group 3 showed enhanced antibody FcγR binding against wild-type and variants compared to Groups 1 and 2, showing a dose-dependent enhancement of immunity conferred by the SCB-2019 vaccine. Moreover, from day 15 after vaccination, Group 3 exhibited higher IgG3 and FcγR binding across variants of concerns, including Omicron and its subvariants, compared to the ChAdOx1-boosted individuals. Overall, this highlights the potential of SCB-2019 as a cost-efficient boosting regimen effective across variants of concerns.

SCB-2019 protein vaccine as heterologous booster of neutralizing activity against SARS-CoV-2 Omicron variants after immunization with other COVID-19 vaccines.

We assessed the non-inferiority of homologous boosting compared with heterologous boosting with the recombinant protein vaccine, SCB-2019, in adults previously immunized with different COVID-19 vaccines. Three equal cohorts (N ~ 420) of Philippino adults (18-80 years) previously immunized with Comirnaty, CoronaVac or Vaxzevria COVID-19 vaccines were randomized 1:1 to receive homologous or heterologous (SCB-2019) boosters. Neutralizing antibodies against prototype SARS-CoV-2 (Wuhan-Hu-1) were measured in all participants and against Delta variant and Omicron sub-lineages in subsets (30‒50 per arm) 15 days after boosting. Participants recorded solicited adverse events for 7 days and unsolicited and serious adverse events until Day 60. Prototype SARS-CoV-2 neutralizing responses on Day 15 after SCB-2019 were statistically non-inferior to homologous Vaxzevria boosters, superior to CoronaVac, but lower than homologous Comirnaty. Neutralizing responses against Delta and Omicron BA.1, BA.2, BA.4 and BA.5 variants after heterologous SCB-2019 were higher than homologous CoronaVac or Vaxzevria, but lower than homologous Comirnaty. Responses against Omicron BF.7, BQ.1.1.3, and XBB1.5 following heterologous SCB-2019 were lower than after homologous Comirnaty booster but significantly higher than after Vaxzevria booster. SCB-2019 reactogenicity was similar to CoronaVac or Vaxzevria, but lower than Comirnaty; most frequent events were mild/moderate injection site pain, headache and fatigue. No vaccine-related serious adverse events were reported. Heterologous SCB-2019 boosting was well tolerated and elicited neutralizing responses against all tested SARS-COV-2 viruses including Omicron BA.1, BA.2, BA.4, BA.5, BF.7, BQ.1.1.3, and XBB1.5 sub-lineages that were non-inferior to homologous boosting with CoronaVac or Vaxzevria, but not homologous Comirnaty booster.

The faces behind vaccination: unpacking the attitudes, knowledge, and practices of staff of Cameroon's Expanded program on Immunization.

BACKGROUND: Immunization is regarded as one of the most cost-effective public health interventions in global health. However, its cost-effectiveness depends greatly on the knowledge and skills of vaccinators. With the growing complexity of immunization programs, the need for a well-trained vaccination workforce cannot be overemphasized. In this study, we assessed the knowledge, attitudes, and practices among vaccination staff in Cameroon. METHODS: Through a descriptive cross-sectional design, we used structured questionnaires and observation guides to collect data from vaccination staff in health facilities that were selected by a multistage sampling method. Data were analyzed using STATA 13 software. RESULTS: Overall, we collected data from Expanded Program on Immunization focal staff in 265 health facilities across 68 health districts. Over half (53%) of the surveyed facilities were found in rural areas. Nearly two-thirds of health facilities had immunization focal staff with knowledge gaps for each of the four basic immunization indicators assessed. In other words, only 37% of staff knew how to estimate coverages, 36% knew how to inteprete the EPI monitoring curve, 35% knew how to prepare vaccine orders, and 37% knew how to estimate vaccine wastage. In terms of practices, staff waited for more than ten children to be present before opening a 20-dose vaccine vial in 63% of health facilities, and more than five children to be present before opening a 10-dose vaccine vial in 80% of surveyed facilities. Provision of vaccine-specific information (informing caregiver about vaccine received, explanation of benefits and potential side effects) during immunization sessions was suboptimal for the most part. CONCLUSION: This study suggests marked deficits in immunization knowledge among vaccination staff and exposes common attitudes and practices that could contribute to missed opportunities for vaccination and hinder vaccination coverage and equity in Cameroon. Our findings highlight the urgent need to invest in comprehensive capacity building of vaccination staff in Cameroon, especially now that the immunization program is becoming increasingly complex.

Development of a composite scoring system to rank communities at high risk of zero-dose children in Cameroon: A geospatial analysis.

Background: Despite growing efforts to improve access to vaccination, millions of children, especially in developing countries, have not received a single dose of diphtheria, tetanus, and pertussis (DTP) vaccine. Consequently, they are often called zero-dose children (ZDC). With limited health resources, prioritising communities for rapid and mass zero-dose catch-up vaccination in missed communities to avert epidemic outbreaks is complicated by unreliable denominators used to compute vaccination coverages. Incorporating other indicators of access and utilisation of vaccination services can help with identifying and ranking missed communities based on the likelihood of finding ZDC. We described the process of generating a scoring method to rank health areas in Cameroon based on their likelihood of containing ZDC. Methods: We used geospatial analysis to compute and aggregate health area characteristics, including hard-to-reach (HTR) areas (defined as areas of settlement above a one- (for urban areas) or 15-kilometre radius (for rural areas) beyond a vaccinating health facility), amount of area covered by slums and new area settlement, and percentage of children unvaccinated for DTP-1. We attributed a weight based on the ability to limit accessibility or utilisation of vaccination services to each characteristic and computed the score as a weighted average of health area characteristics. The health area score ranged from 0 to 1, with higher scores representing a higher likelihood of containing ZDC. We stratified the analysis by rural and urban health areas. Results: We observed substantial district and regional variations in health area scores, with hotspots health areas (administrative level 4) observed in the Far North (0.83), North (0.81), Adamawa (0.80), East (0.75), and South West (0.67) regions. The Adamawa region had the highest percentage of health areas with the highest score (78%), followed by the East (50%), West (48%), and North (46%) regions. For most regions (Far North, South, South West, Littoral, West, and North West), DTP-1 contributed the most to the score. However, HTR settlement areas within a health area contributed substantially to the overall score in the East, North, and Adamawa regions. Conclusions: We found substantial variations in health area scores with hotspots in the Far North, North, Adamawa, East, and South West regions. Although DTP-1 could be used as an indicator to identify health areas with ZDC for most communities, HTR settlement area was a valuable indicator in ranking priority health areas in the East, North, and Adamawa regions, further emphasising the need to consider other indicators before prioritisation.

Assessment of immunization data management practices in Cameroon: unveiling potential barriers to immunization data quality.

BACKGROUND: One crucial obstacle to attaining universal immunization coverage in Sub-Saharan Africa is the paucity of timely and high-quality data. This challenge, in part, stems from the fact that many frontline immunization staff in this part of the world are commonly overburdened with multiple data-related responsibilities that often compete with their clinical tasks, which in turn could affect their data collection practices. This study assessed the data management practices of immunization staff and unveiled potential barriers impacting immunization data quality in Cameroon. METHODS: A descriptive cross-sectional study was conducted, involving health districts and health facilities in all 10 regions in Cameroon selected by a multi-stage sampling scheme. Structured questionnaires and observation checklists were used to collect data from Expanded Program of Immunization (EPI) staff, and data were analyzed using STATA VERSION 13.0 (StataCorp LP. 2015. College Station, TX). RESULTS: A total of 265 facilities in 68 health districts were assessed. There was limited availability of some data recording tools like vaccination cards (43%), maintenance registers (8%), and stock cards (57%) in most health facilities. Core data collection tools were incompletely filled in a significant proportion of facilities (37% for registers and 81% for tally sheets). Almost every health facility (89%) did not adhere to the recommendation of filling tally sheets during vaccination; the filling was instead done either before (51% of facilities) or after (25% of facilities) vaccinating several children. Moreso, about 8% of facilities did not collect data on vaccine administration. About a third of facilities did not collect data on stock levels (35%), vaccine storage temperatures (21%), and vaccine wastage (39%). CONCLUSION: Our findings unveil important gaps in data collection practices at the facility level that could adversely affect Cameroon's immunization data quality. It highlights the urgent need for systematic capacity building of frontline immunization staff on data management capacity, standardizing data management processes, and building systems that ensure constant availability of data recording tools at the facility level.

Influenza Vaccination during Pregnancy: A Descriptive Study of the Knowledge, Beliefs, and Practices of Mexican Gynecologists and Family Physicians.

BACKGROUND: Influenza in pregnancy is associated with elevated morbidity and mortality. Influenza vaccines are safe and effective in pregnancy. There are no Mexican surveys of physicians on knowledge, beliefs, and practices towards influenza and influenza immunization during pregnancy. METHODS: A 32-question descriptive survey was conducted, addressing the general knowledge of influenza as well as beliefs and practices regarding influenza vaccination during pregnancy among Mexican physicians responsible for prenatal care, traditionally Obstetricians (OBGYNs) and Family Physicians (FPs). RESULTS: A total of 206 surveys were available, 98 (47.6%) from OBGYNs and 108 (52.4%) from FPs, representing an estimated 2472 daily pregnancy consultations. In total, 54 of the 206 respondents (26.2%) were not aware that influenza is more severe during pregnancy, 106 of the 206 respondents (51.5%) ignored the potential side effects of influenza infection on the fetus, and 56.8% did not know when to vaccinate pregnant women. Pregnancy as a risk factor for developing influenza complications was only known by 99 of the 206 respondents (48.1%), and 6.1% believed that vaccination does not confer protection to the fetus. CONCLUSIONS: The current beliefs of Mexican OBGYNs and FPs for both influenza morbidity and mortality, and the importance of influenza vaccination during pregnancy are suboptimal. The drivers of these beliefs should be assessed to improve influenza vaccination recommendations, as knowledge alone is not sufficient.

Pertussis antibodies and vaccination coverage among healthcare professionals in Brazil is inadequate: A cross-sectional serological study.

INTRODUCTION: Worldwide, tetanus-diphtheria-acellular pertussis (Tdap) vaccination coverage of healthcare professionals (HCPs) is below 40%, but this data is not available for Brazil. We hypothesize that a high number of HCPs are not immune to pertussis in Brazil. Main objective was to determine the seroprevalence of anti-pertussis toxin (anti-PT IgG) among HCPs. Secondary objectives were to evaluate Tdap vaccination coverage, to assess predictive factors associated with anti-PT IgG, and to estimate the decay of anti-PT IgG and time to Tdap vaccination. METHODS: Observational cross-sectional serological study in 352 HCPs who worked at São Paulo Hospital - Federal University of São Paulo (UNIFESP) in 2020, approved by UNIFESP Ethics Committee. Data collected included sociodemographics, knowledge about Tdap, and vaccination status. Anti-PT IgG were quantified by ELISA: <10 IU/mL seronegative and ≥ 10-1000 IU/mL seropositive. Titers ≥ 10-50 IU/mL were classified low positivity, indicating no recent B. pertussis infection or Tdap vaccination; >50 IU/mL high positivity, indicating recent B. pertussis infection or Tdap vaccination, and > 100 IU/mL as acute B. pertussis infection or Tdap vaccination in the previous year. Comparisons were done by Chi-square test, multivariable logistic regression, and Pearsons correlation, at 5% p-level. RESULTS: 331/352 HCPs were not aware the Brazilian National Immunization Program recommends Tdap for all HCPs and pregnant women. 68/339 HCPs received Tdap (mean 3.1 ± 2.0 years). 55/352 were seronegative for pertussis, all unvaccinated. 56/271 with no history of Tdap vaccination had high positivity. The probability of anti-PT IgG > 50 IU/mL was 11.5 times higher in Tdap vaccinated HCPs than in non-vaccinated (p < 0.001). There was a weak but significant correlation between anti-PT IgG and interval of Tdap vaccination (r = 0.404; p = 0.001). Anti-PT IgG dropped 5 IU/mL/year (p = 0.001). CONCLUSION: Better education of HCPs on needs and benefits of Tdap vaccination is critical. Goals must be to improve HCPs vaccination coverage.

The role of a genetically stable, novel oral type 2 poliovirus vaccine in the poliomyelitis endgame.

Poliovirus infection causes paralysis in up to 1 in 200 infected persons. The use of safe and effective inactivated poliovirus vaccines and live attenuated oral poliovirus vaccines (OPVs) means that only two pockets of wild-type poliovirus type 1 remain, in Afghanistan and Pakistan. However, OPVs can revert to virulence, causing outbreaks of circulating vaccine-derived poliovirus (cVDPV). During 2020-2022, cVDPV type 2 (cVDPV2) was responsible for 97-99% of poliomyelitis cases, mainly in Africa. Between January and August 2022, cVDPV2 was detected in sewage samples in Israel, the United Kingdom and the United States of America, where a case of acute flaccid paralysis caused by cVDPV2 also occurred. The Pan American Health Organization has warned that Brazil, the Dominican Republic, Haiti and Peru are at very high risk for the reintroduction of poliovirus and an additional eight countries in Latin America are at high risk, following dropping vaccination rates (average 80% coverage in 2022). Sabin type 2 monovalent OPV has been used to control VDPV2 outbreaks, but its use could also lead to outbreaks. To address this issue, a more genetically stable, novel OPV2 (nOPV2) was developed against cVDPV2 and in 2020 was granted World Health Organization Emergency Use Listing. Rolling out a novel vaccine under the Emergency Use Listing in mass settings to contain outbreaks requires unique local regulatory and operational preparedness.

La infección por poliovirus ocasiona parálisis en hasta 1 de cada 200 personas infectadas. La utilización de vacunas con poliovirus inactivados y de vacunas antipoliomielíticas orales con poliovirus vivos atenuados (OPV) seguras y eficaces ha logrado que solo queden dos focos de poliovirus salvaje de tipo 1, en Afganistán y Pakistán. Sin embargo, las vacunas con OPV pueden revertir a la virulencia y producir brotes de poliovirus circulantes de origen vacunal (cVDPV). Durante el período 2020-2022, el cVDPV de tipo 2 (cVDPV2) fue la causa del 97-99% de los casos de poliomielitis, sobre todo en África. Entre enero y agosto del 2022, se encontró el cVDPV2 en muestras de aguas residuales en Estados Unidos de América, donde se produjo un caso de parálisis flácida aguda por el cVDPV2, Israel y Reino Unido y. La Organización Panamericana de la Salud ha advertido que, tras la caída de las tasas de vacunación (con una cobertura promedio del 80% en el 2022), Brasil, Haití, Perú y República Dominicana corren un riesgo muy alto de reintroducción del poliovirus, en tanto que otros ocho países de América Latina se encuentran en una situación de alto riesgo. La OPV monovalente de tipo 2 de Sabin se ha utilizado para controlar los brotes de VDPV2, pero su empleo también podría ocasionar brotes. Para hacer frente a este problema, se creó una nueva OPV2 (nOPV2) contra el cVDPV2, genéticamente más estable, que en el 2020 se incluyó en la lista de uso en emergencias de la Organización Mundial de la Salud. El despliegue a gran escala de una nueva vacuna incluida en la lista de uso en emergencias con el fin de contener los brotes exige una extraordinaria preparación regulatoria y operativa local.

A infecção pelo poliovírus causa paralisia em 1 de cada 200 pessoas infectadas. O uso de vacinas seguras e eficazes, tanto vacinas inativadas contra o poliovírus quanto vacinas orais contendo poliovírus atenuado (VOP), significa que restam apenas dois bolsões de poliovírus selvagem tipo 1, um no Afeganistão e outro no Paquistão. No entanto, a VOP pode reverter à virulência, causando surtos de poliovírus circulante derivado de vacina (cPVDV). No período 2020-2022, o cPVDV tipo 2 (cPVDV2) foi responsável por 97% a 99% dos casos de poliomielite, principalmente na África. Entre janeiro e agosto de 2022, o cPVDV2 foi detectado em amostras de esgoto em Israel, no Reino Unido e nos Estados Unidos da América, onde também houve um caso de paralisia flácida aguda causada pelo cPVDV2. A Organização Pan-Americana da Saúde alertou que, devido à queda nas taxas de vacinação (cobertura média de 80% em 2022), o Brasil, o Haiti, o Peru e a República Dominicana correm um risco muito alto de reintrodução do poliovírus e outros oito países da América Latina correm um risco alto. A VOP monovalente Sabin tipo 2 tem sido usada para controlar surtos de PVDV2, mas seu uso também pode levar a surtos. Para resolver esse problema, foi desenvolvida uma nova VOP2 (nVOP2), mais estável geneticamente, para combater o cPVDV2. Em 2020, a nVOP2 entrou na Lista de Uso Emergencial da Organização Mundial da Saúde. A distribuição de uma nova vacina incluída na Lista de Uso Emergencial em contextos de massa para conter surtos requer medidas originais de preparação operacional e regulatória em âmbito local.

Immunogenicity, safety and reactogenicity of heterologous (third dose) booster vaccination with a full or fractional dose of two different COVID-19 vaccines: A phase 4, single-blind, randomized controlled trial in adults.

In this phase 4 study we assessed boosting with fractional doses of heterologous COVID-19 vaccines in Brazilian adults primed with two doses of CoronaVac (Sinovac/Butantan, São Paulo, Brazil) at least 4 months previously. Participants received either full-dose of ChAdOx1-S (Group 1, n = 232), a half dose of ChAdOx1-S (Group 2, n = 236), or a half dose of BNT162b2 (Group 3, n = 234). The primary objective was to show 80% seroresponse rates (SRR) 28 d after vaccination measured as IgG antibodies against a prototype SARS-CoV-2 spike-protein. Safety was assessed as solicited and unsolicited adverse events. At baseline all participants were seropositive, with high IgG titers overall. SRR at Day 28 were 34.3%, 27.1% and 71.2%, respectively, not meeting the primary objective of 80%, despite robust immune responses in all three groups with geometric mean-fold rise (GMFR) in IgG titers of 3.39, 2.99 and 7.42, respectively. IgG immune responses with similar GMFR were also observed against SARS-CoV-2 variants, Alpha, Beta, Delta, Gamma and D614G. In subsets (n = 35) of participants GMFR of neutralizing immune responses against live prototype SARS-CoV-2 virus and Omicron BA.2 were similar to the IgG responses as were pseudo-neutralizing responses against SARS-CoV-2 prototype and Omicron BA.4/5 variants. All vaccinations were well tolerated with no vaccine-related serious adverse events and mainly transient mild-to-moderate local and systemic reactogenicity. Heterologous boosting with full or half doses of ChAdOx1-S or a half dose of BNT162b2 was safe and immunogenic in CoronaVac-primed adults, but seroresponse rates were limited by high baseline immunity.

Superior Boosting of Neutralizing Titers Against Omicron SARS-CoV-2 Variants by Heterologous SCB-2019 Vaccine vs a Homologous Booster in CoronaVac-Primed Adults.

BACKGROUND: We compared homologous and heterologous boosting in adults in the Philippines primed with 2 or 3 doses of CoronaVac, with recombinant protein vaccine, SCB-2019. METHODS: CoronaVac-immunized adults (18-72 years) received a homologous or heterologous full or half dose SCB-2019 booster. We assessed all neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days and NAb against SARS-CoV-2 Delta and Omicron variants in subsets (30‒50 per arm). Participants recorded adverse events. RESULTS: In 2-dose CoronaVac-primed adults prototype NAb geometric mean titers (GMT) were 203 IU/mL (95% confidence interval [CI], 182-227) and 939 IU/mL (95% CI, 841-1049) after CoronaVac and SCB-2019 boosters; the GMT ratio (4.63; 95% CI, 3.95-5.41) met predefined noninferiority and post-hoc superiority criteria. After 3-dose CoronaVac-priming prototype NAb GMTs were 279 IU/mL (95% CI, 240-325), 1044 IU/mL (95% CI, 898-1213), and 668 IU/mL (95% CI, 520-829) following CoronaVac, full and half-dose SCB-2019 boosters, respectively. NAb GMT ratios against Delta and Omicron comparing SCB-2019 with CoronaVac were all greater than 2. Mild to moderate reactogenicity was evenly balanced between groups. No vaccine-related serious adverse events were reported. CONCLUSIONS: Full or half dose SCB-2019 boosters were well tolerated with superior immunogenicity than homologous CoronaVac, particularly against newly emerged variants. Clinical Trials Registration. NCT05188677.

The role of a genetically stable, novel oral type 2 poliovirus vaccine in the poliomyelitis endgame

[ABSTRACT]. Poliovirus infection causes paralysis in up to 1 in 200 infected persons. The use of safe and effective inactivated poliovirus vaccines and live attenuated oral poliovirus vaccines (OPVs) means that only two pockets of wild- type poliovirus type 1 remain, in Afghanistan and Pakistan. However, OPVs can revert to virulence, causing outbreaks of circulating vaccine-derived poliovirus (cVDPV). During 2020–2022, cVDPV type 2 (cVDPV2) was responsible for 97–99% of poliomyelitis cases, mainly in Africa. Between January and August 2022, cVDPV2 was detected in sewage samples in Israel, the United Kingdom and the United States of America, where a case of acute flaccid paralysis caused by cVDPV2 also occurred. The Pan American Health Organization has warned that Brazil, the Dominican Republic, Haiti and Peru are at very high risk for the reintroduction of polio- virus and an additional eight countries in Latin America are at high risk, following dropping vaccination rates (average 80% coverage in 2022). Sabin type 2 monovalent OPV has been used to control VDPV2 outbreaks, but its use could also lead to outbreaks. To address this issue, a more genetically stable, novel OPV2 (nOPV2) was developed against cVDPV2 and in 2020 was granted World Health Organization Emergency Use Listing. Rolling out a novel vaccine under the Emergency Use Listing in mass settings to contain outbreaks requires unique local regulatory and operational preparedness.

[RESUMEN]. La infección por poliovirus ocasiona parálisis en hasta 1 de cada 200 personas infectadas. La utilización de vacunas con poliovirus inactivados y de vacunas antipoliomielíticas orales con poliovirus vivos atenuados (OPV) seguras y eficaces ha logrado que solo queden dos focos de poliovirus salvaje de tipo 1, en Afganistán y Pakistán. Sin embargo, las vacunas con OPV pueden revertir a la virulencia y producir brotes de poliovi- rus circulantes de origen vacunal (cVDPV). Durante el período 2020-2022, el cVDPV de tipo 2 (cVDPV2) fue la causa del 97-99% de los casos de poliomielitis, sobre todo en África. Entre enero y agosto del 2022, se encontró el cVDPV2 en muestras de aguas residuales en Estados Unidos de América, donde se produjo un caso de parálisis flácida aguda por el cVDPV2, Israel y Reino Unido y. La Organización Panamericana de la Salud ha advertido que, tras la caída de las tasas de vacunación (con una cobertura promedio del 80% en el 2022), Brasil, Haití, Perú y República Dominicana corren un riesgo muy alto de reintroducción del poliovirus, en tanto que otros ocho países de América Latina se encuentran en una situación de alto riesgo. La OPV mon- ovalente de tipo 2 de Sabin se ha utilizado para controlar los brotes de VDPV2, pero su empleo también podría ocasionar brotes. Para hacer frente a este problema, se creó una nueva OPV2 (nOPV2) contra el cVDPV2, genéticamente más estable, que en el 2020 se incluyó en la lista de uso en emergencias de la Organización Mundial de la Salud. El despliegue a gran escala de una nueva vacuna incluida en la lista de uso en emergen- cias con el fin de contener los brotes exige una extraordinaria preparación regulatoria y operativa local.

[RESUMO]. A infecção pelo poliovírus causa paralisia em 1 de cada 200 pessoas infectadas. O uso de vacinas seguras e eficazes, tanto vacinas inativadas contra o poliovírus quanto vacinas orais contendo poliovírus atenuado (VOP), significa que restam apenas dois bolsões de poliovírus selvagem tipo 1, um no Afeganistão e outro no Paquistão. No entanto, a VOP pode reverter à virulência, causando surtos de poliovírus circulante derivado de vacina (cPVDV). No período 2020-2022, o cPVDV tipo 2 (cPVDV2) foi responsável por 97% a 99% dos casos de poliomielite, principalmente na África. Entre janeiro e agosto de 2022, o cPVDV2 foi detectado em amostras de esgoto em Israel, no Reino Unido e nos Estados Unidos da América, onde também houve um caso de paralisia flácida aguda causada pelo cPVDV2. A Organização Pan-Americana da Saúde alertou que, devido à queda nas taxas de vacinação (cobertura média de 80% em 2022), o Brasil, o Haiti, o Peru e a República Dominicana correm um risco muito alto de reintrodução do poliovírus e outros oito países da América Latina correm um risco alto. A VOP monovalente Sabin tipo 2 tem sido usada para controlar surtos de PVDV2, mas seu uso também pode levar a surtos. Para resolver esse problema, foi desenvolvida uma nova VOP2 (nVOP2), mais estável geneticamente, para combater o cPVDV2. Em 2020, a nVOP2 entrou na Lista de Uso Emergencial da Organização Mundial da Saúde. A distribuição de uma nova vacina incluída na Lista de Uso Emergencial em contextos de massa para conter surtos requer medidas originais de preparação operacional e regulatória em âmbito local.

SARS-CoV-2 and Dengue Coinfection in Filipino Children: Epidemiology Profile, Clinical Presentation and Outcomes.

BACKGROUND: The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in dengue-endemic regions has raised concern on the possibility of coinfection, especially in children who bear the highest burden of illness. This study determined the incidence and described the profile of Filipino children with SARS-CoV-2 and dengue coinfection, and compared disease severity and outcome in children with coinfection to a matched group of children with SARS-CoV-2 monoinfection. METHODS: This was a retrospective matched cohort study of pediatric patients 0-18 years old diagnosed with SARS-CoV-2 and dengue coinfection or SARS-CoV-2 monoinfection in the Philippines and reported to the Surveillance and Analysis of Coronavirus disease 2019 (COVID-19) in Children Nationwide registry from March 01, 2020 to June 30, 2022. RESULTS: A total of 3,341 SARS-CoV-2 infections in children were reported. The SARS-CoV-2 and dengue coinfection incidence is 4.34% (n = 145). We matched 120 coinfections to monoinfections according to age, gender and timing of infection. More coinfection cases were classified as mild or moderate COVID-19, whereas more asymptomatic cases were seen in those with monoinfection. Rates were similar for severe and critical COVID-19 in both groups. Coinfections predominantly presented with typical dengue symptoms rather than COVID-19 symptoms and laboratory parameters. No differences in outcomes were observed between coinfection and monoinfection. The case fatality rates are 6.7% for coinfection and 5.0% for monoinfection. CONCLUSIONS: One in every 25 SARS-CoV-2 infections had a dengue coinfection. Continued surveillance is needed to establish the interaction of SARS-CoV-2 and dengue virus, evaluate the impact of COVID-19 and/or dengue vaccination on coinfection and monitor complications of coinfection.

Investigating the Possible Reasons for the Low Reported Morbidity and Mortality of COVID-19 in African Countries: An Integrative Review.

BACKGROUND: COVID-19 has impacted the world differentially with the highest mortality and morbidity rate burden in Europe and the USA and the lowest mortality and morbidity burden in Africa. This study aims to investigate the possible reasons why Africa recorded the lowest COVID-19 mortality and morbidity. METHODS: The following search terms were used PubMed database: ["mortalit*" (tw) OR "morbidit*" (tw) AND "COVID-19" (tw) AND "Africa" (tw)]. Studies that discuss a factor for the low COVID-19 burden in Africa have a defined methodology, discuss its research question and mention its limitations are selected for review. Data from the final articles were extracted using a data collection tool. RESULTS: Twenty-one studies were used in this integrative review. Results were grouped into 10 themes, which are younger African population, lower health capacity, weather, vaccines and drugs, effective pandemic response, lower population density and mobility, African socioeconomic status, lower prevalence of comorbidities, genetic difference and previous infection exposure. The low COVID-19 mortality and morbidity in Africa is largely a result of a combined effect of the younger African population and underreporting of COVID-19 cases. CONCLUSIONS: There is a need to strengthen the health capacities of African countries. Moreover, African countries that have other health problem priorities may use a tailored approach to vaccinating the elderly. More definitive studies are needed to know the role of BCG vaccination, weather, genetic makeup and prior infection exposure in the differential impact of the COVID-19 pandemic.

Vaccination strategies for people living with inborn errors of metabolism in Brazil

Abstract Objective: Through a literature review, make recommendations regarding immunizations in people living with Inborn Error of Metabolism (IEM) in Brazil, assess the possible impact on metabolic decompensations after immunization, and if this specific population may have an impaired immune response to vaccines. Source of data: The MeSH Terms vaccination OR vaccine OR immunization associated with the term inborn error of metabolism AND recommendation were used in combination with search databases. Only articles published after 1990, in the languages English, Spanish, French or Portuguese, human-related were included. Synthesis of data: A total of 44 articles were included to make the following recommendations. Individuals with IEMs need to be up to date with their immunizations. Regarding which vaccines should be offered, children and adults should follow the routine immunization schedules locally available, including the COVID-19 vaccines. The only exception is the rotavirus vaccine for hereditary fructose intolerance. The benefit of immunization outweighs the very low risk of metabolic decompensation. Since not all patients will have an adequate immune response, measuring antibody conversion and titers is recommended Conclusions: All patients should receive age-appropriate immunizations in their respective schedules without delays. The only situation when vaccination may be contraindicated is with oral rotavirus vaccine in hereditary fructose intolerance. Monitoring the levels of antibodies should be done to detect any immune dysfunction or the necessity for boosters. A personalized immunization schedule is ideal for patients with IEMs. The reference organizations could improve their recommendations to address all IEMs, not only some of them.

The need and challenges for development of vaccines against emerging infectious diseases

Abstract Objective: To identify and describe learnings from past pandemics and to suggest a framework for vaccine development as part of epi/pandemic readiness. Source of data: Articles/ reviews/letters on pandemic preparedness/ vaccines published between 2005 and 2022 in PubMed, MEDLINE, MedRxiv, BioRxiv, Research Square, Gates Open Research; who. int, cepi.net, visualcapitalist.com, airfinity.com, ted.com websites; press releases. Summary of findings: Disease pandemics caused by emerging pathogens impacted the social development, health and wealth of most societies in human history. In an outbreak, the first months determine its course. To block an exponential spread and the development of an epi/ pandemic early, vaccine availability in sufficient quantities is of paramount importance. It is inevitable that new human viruses will emerge. Any future pandemic will come likely from RNA viruses through zoonotic or vector transmission, but we cannot predict when or where "Disease X" will strike. Public health, scientific and societal readiness plans need to include: continuous identification of new viruses in common mammalian reservoir hosts; continuous epidemiological surveillance, including wastewater sampling; establishment of prototype vaccine libraries against various virus families sharing functional and structural properties; testing of various and innovative vaccine platforms including mRNA, vector, nasal or oral vaccines for suitability by virus family; functional clinical trial sites and laboratory networks in various geographies; more efficient phasing of preclinical and clinical activities; global harmonization and streamlining of regulatory requirements including pre-established protocols; and societal preparedness including combating any pandemic of misinformation. Conclusions: "Outbreaks are unavoidable, pandemics are optional".