Child COVID-19 vaccine uptake among participants of the 2015 Pelotas (Brazil) Birth Cohort Study.

OBJECTIVE: To analyze COVID-19 vaccine uptake in children and to investigate factors associated with two outcomes variables: (a) not even beginning; (b) not completing the COVID-19 vaccine series. METHODS: We used data of children aged 6-7 years from the 2015 Pelotas c Birth Cohort Study. COVID-19 vaccination status was collected from immunization cards and National Immunization Program Information System. Adjusted analyses were performed using a hierarchical model to identify factors associated with the two study outcomes. RESULTS: Among 3867 children, 20.7 % (95 % CI, 19.5 %-22.0 %) did not even begin the 2-dose primary COVID-19 vaccine series, and 28.2 % (95 % CI, 26.6 %-29.8 %) did not complete the series with the second dose. Children not even beginning the COVID-19 vaccine series were more likely to have a White mother, not to have obesity, to have a history of COVID-19 infection, to have received non-recommended drugs for COVID-19, to be afraid of needles, and to have an incomplete diphtheria-tetanus-pertussis (DTP) and poliovirus immunization schedule. Not completing the 2-dose series was associated with lower maternal age and education, mother's self-identification as White or Brown, lower household income, lack of access to health services, not having completed the DTP and poliovirus immunization schedule and living with a person with a history of infection with COVID-19. CONCLUSION: The results highlight a vaccine-hesitant parents' group who chose not beginning the COVID-19 vaccine series of their children and, another group of parents who failure to complete the child's series due to difficulty accessing health services.

Immune responses during COVID-19 breakthrough cases in vaccinated children and adolescents.

Background: Vaccine effectiveness against SARS-CoV-2 infection has been somewhat limited due to the widespread dissemination of the Omicron variant, its subvariants, and the immune response dynamics of the naturally infected with the virus. Methods: Twelve subjects between 3-17 years old (yo), vaccinated with two doses of CoronaVac®, were followed and diagnosed as breakthrough cases starting 14 days after receiving the second dose. Total IgGs against different SARS-CoV-2 proteins and the neutralizing capacity of these antibodies after infection were measured in plasma. The activation of CD4+ and CD8+ T cells was evaluated in peripheral blood mononuclear cells stimulated with peptides derived from the proteins from the wild-type (WT) virus and Omicron subvariants by flow cytometry, as well as different cytokines secretion by a Multiplex assay. Results: 2 to 8 weeks post-infection, compared to 4 weeks after 2nd dose of vaccine, there was a 146.5-fold increase in neutralizing antibody titers against Omicron and a 38.7-fold increase against WT SARS-CoV-2. Subjects showed an increase in total IgG levels against the S1, N, M, and NSP8 proteins of the WT virus. Activated CD4+ T cells showed a significant increase in response to the BA.2 subvariant (p<0.001). Finally, the secretion of IL-2 and IFN-γ cytokines showed a discreet decrease trend after infection in some subjects. Conclusion: SARS-CoV-2 infection in the pediatric population vaccinated with an inactivated SARS-CoV-2 vaccine produced an increase in neutralizing antibodies against Omicron and increased specific IgG antibodies for different SARS-CoV-2 proteins. CD4+ T cell activation was also increased, suggesting a conserved cellular response against the Omicron subvariants, whereas Th1-type cytokine secretion tended to decrease. Clinical Trial Registration: clinicaltrials.gov #NCT04992260.

Computational method for designing vaccines applied to virus-like particles (VLPs) as epitope carriers.

Nonenveloped virus-like particles (VLPs) are self-assembled oligomeric structures composed of one or more proteins that originate from diverse viruses. Because these VLPs have similar antigenicity to the parental virus, they are successfully used as vaccines against cognate virus infection. Furthermore, after foreign antigenic sequences are inserted in their protein components (chimVLPs), some VLPs are also amenable to producing vaccines against pathogens other than the virus it originates from (these VLPs are named platform or epitope carrier). Designing chimVLP vaccines is challenging because the immunogenic response must be oriented against a given antigen without altering stimulant properties inherent to the VLP. An important step in this process is choosing the location of the sequence modifications because this must be performed without compromising the assembly and stability of the original VLP. Currently, many immunogenic data and computational tools can help guide the design of chimVLPs, thus reducing experimental costs and work. In this study, we analyze the structure of a novel VLP that originate from an insect virus and describe the putative regions of its three structural proteins amenable to insertion. For this purpose, we employed molecular dynamics (MD) simulations to assess chimVLP stability by comparing mutated and wild-type (WT) VLP protein trajectories. We applied this procedure to design a chimVLP that can serve as a prophylactic vaccine against the SARS-CoV-2 virus. The methodology described in this work is generally applicable for VLP-based vaccine development.

Guillain-Barre syndrome before and during the COVID-19 pandemic in a referral center of Mexico.

BACKGROUND: During the COVID-19 pandemic, an increase in the number of Guillain-Barre syndrome (GBS) cases has been reported. OBJECTIVE: To describe the clinical characteristics and prognosis of patients with GBS before and during the COVID-19 pandemic. MATERIAL AND METHODS: Prospective cohort of GBS patients divided in two subgroups: before (2018-2019) and during (2020-2021) the COVID-19 pandemic. Clinical and paraclinical characteristics, as well as deaths, were recorded. A good prognosis was defined as independent ambulation recovery at three months. RESULTS: Two-hundred and one patients were included (123 during and 78 before the pandemic), out of whom 69% were males; age was 45 ± 16 years, and there was 2.5% of in-hospital deaths. During the pandemic, a higher frequency of the demyelinating variant (50%), bulbar cranial nerves involvement (44% vs. 28%), prior history of vaccination (16% vs. 0%), and a lower MRC score (30 ± 16.7 vs. 34.3 ± 17.7) were documented. An increase in the number of cases was observed from July to September (38 vs. 13). There were no significant differences in independent ambulation recovery or in the number of deaths. CONCLUSIONS: During the COVID-19 pandemic, a higher number of GBS cases were treated, out of which 16% were associated with the SARS-CoV-2 vaccine; patients treated during the pandemic did not have a worse prognosis.

ANTECEDENTES: Durante la pandemia de COVID-19 se ha reportado incremento de casos de síndrome de Guillain-Barré (SGB). OBJETIVO: Describir características clínicas y pronóstico de pacientes con SGB antes y durante la pandemia de COVID-19. MATERIAL Y MÉTODOS: Cohorte prospectiva de pacientes con SGB estratificados en dos subgrupos: antes (2018-2019) y durante (2020-2021) la pandemia de COVID-19. Se registraron características clínicas, paraclínicas y defunciones. Se definió como buen pronóstico a la recuperación de la marcha independiente a los tres meses. RESULTADOS: Se incluyeron 201 pacientes (123 durante la pandemia y 78 antes), 69 % del sexo masculino, edad de 45 ± 16 años, 2.5 % de muertes intrahospitalarias. Durante la pandemia se observó mayor frecuencia de la variante desmielinizante (50 %), afección de nervios craneales bulbares (44 % versus 28 %), antecedente de vacunación (16 % versus 0 %) y menor puntuación en la escala MRC (30 ± 16.7 versus 34.3 ± 17.7); se observó aumento de casos de julio a septiembre (38 versus 13). No existieron diferencias significativas en la recuperación de la marcha independiente y número de defunciones. CONCLUSIONES: Durante la pandemia se atendió mayor número de casos de SGB, 16 % asociado a la vacuna contra SARS-CoV-2; los pacientes no presentaron peor pronóstico.

Side Effects of COVID-19 Vaccines in Pregnant and Lactating Mexican Women and Breastfed Infants: A Survey-Based Study.

COVID-19 vaccines' safety has been extensively studied; however, further analysis is required in pregnant women, nursing mothers, and breastfed infants. Our aim was to compare the extension and severity of self-reported COVID-19 vaccine side effects in pregnant and breastfeeding women, and breastfed infants. In this cross-sectional study, COVID-19-vaccinated subjects were enrolled using an online survey in Mexico. Women were classified by pregnancy and breastfeeding status at the time of vaccination (n = 3167). After the first or only dose, there was a trend toward fewer systemic effects in pregnant women (p = 0.06). BNT162b2 (Pfizer-BioNTech) had a higher frequency of local symptoms in pregnancy. Lactating women experienced fewer local symptoms after the first or single dose (p = 0.04) and the opposite occurred after the second dose (p = 0.001). ChAdOx1 (AstraZeneca) increased the chances of developing both local and systemic symptoms after the first dose but decreased them after the second dose. The severity was similar across groups, although the result of lack of association in pregnancy requires studies with a larger sample size. Irritability was the most reported symptom in breastfed infants. This study contributes to the knowledge about the side effects in pregnant and lactating women, and breastfed babies.

Síndrome de Guillain-Barré antes y durante la pandemia de COVID-19 en un centro de referencia de México / Guillain-Barre syndrome before and during the COVID-19 pandemic in a referral center of Mexico

Resumen Antecedentes: Durante la pandemia de COVID-19 se ha reportado incremento de casos de síndrome de Guillain-Barré (SGB). Objetivo: Describir características clínicas y pronóstico de pacientes con SGB antes y durante la pandemia de COVID-19. Material y métodos: Cohorte prospectiva de pacientes con SGB estratificados en dos subgrupos: antes (2018-2019) y durante (2020-2021) la pandemia de COVID-19. Se registraron características clínicas, paraclínicas y defunciones. Se definió como buen pronóstico a la recuperación de la marcha independiente a los tres meses. Resultados: Se incluyeron 201 pacientes (123 durante la pandemia y 78 antes), 69 % del sexo masculino, edad de 45 ± 16 años, 2.5 % de muertes intrahospitalarias. Durante la pandemia se observó mayor frecuencia de la variante desmielinizante (50 %), afección de nervios craneales bulbares (44 % versus 28 %), antecedente de vacunación (16 % versus 0 %) y menor puntuación en la escala MRC (30 ± 16.7 versus 34.3 ± 17.7); se observó aumento de casos de julio a septiembre (38 versus 13). No existieron diferencias significativas en la recuperación de la marcha independiente y número de defunciones. Conclusiones: Durante la pandemia se atendió mayor número de casos de SGB, 16 % asociado a la vacuna contra SARS-CoV-2; los pacientes no presentaron peor pronóstico.

Abstract Background: During the COVID-19 pandemic, an increase in the number of Guillain-Barre syndrome (GBS) cases has been reported. Objective: To describe the clinical characteristics and prognosis of patients with GBS before and during the COVID-19 pandemic. Material and methods: Prospective cohort of GBS patients divided in two subgroups: before (2018-2019) and during (2020-2021) the COVID-19 pandemic. Clinical and paraclinical characteristics, as well as deaths, were recorded. A good prognosis was defined as independent ambulation recovery at three months. Results: Two-hundred and one patients were included (123 during and 78 before the pandemic), out of whom 69 % were males; age was 45 ± 16 years, and there was 2.5 % of in-hospital deaths. During the pandemic, a higher frequency of the demyelinating variant (50 %), bulbar cranial nerves involvement (44 % vs. 28 %), prior history of vaccination (16 % vs. 0 %), and a lower MRC score (30 ± 16.7 vs. 34.3 ± 17.7) were documented. An increase in the number of cases was observed from July to September (38 vs. 13). There were no significant differences in independent ambulation recovery or in the number of deaths. Conclusions: During the COVID-19 pandemic, a higher number of GBS cases were treated, out of which 16 % were associated with the SARS-CoV-2 vaccine; patients treated during the pandemic did not have a worse prognosis.

Effectiveness of an inactivated SARS-CoV-2 vaccine in children and adolescents: a large-scale observational study.

Background: Policymakers urgently need evidence to adequately balance the costs and benefits of mass vaccination against COVID-19 across all age groups, including children and adolescents. In this study, we aim to assess the effectiveness of CoronaVac's primary series among children and adolescents in Chile. Methods: We used a large prospective national cohort of about two million children and adolescents 6-16 years to estimate the effectiveness of an inactivated SARS-CoV-2 vaccine (CoronaVac) in preventing laboratory-confirmed symptomatic SARS-CoV-2 infection (COVID-19), hospitalisation, and admission to an intensive care unit (ICU) associated with COVID-19. We compared the risk of individuals treated with a complete primary immunization schedule (two doses, 28 days apart) with the risk of unvaccinated individuals during the follow-up period. The study was conducted in Chile from June 27, 2021, to January 12, 2022, when the SARS-CoV-2 Delta variant was predominant but other variants of concern were co-circulating, including Omicron. We used inverse probability-weighted survival regression models to estimate hazard ratios of complete immunization over the unvaccinated status, accounting for time-varying vaccination exposure and adjusting for relevant demographic, socioeconomic, and clinical confounders. Findings: The estimated adjusted vaccine effectiveness for the inactivated SARS-CoV-2 vaccine in children aged 6-16 years was 74.5% (95% CI, 73.8-75.2), 91.0% (95% CI, 87.8-93.4), 93.8% (95% CI, 87.8-93.4) for the prevention of COVID-19, hospitalisation, and ICU admission, respectively. For the subgroup of children 6-11 years, the vaccine effectiveness was 75.8% (95% CI, 74.7-76.8) for the prevention of COVID-19 and 77.9% (95% CI, 61.5-87.3) for the prevention of hospitalisation. Interpretation: Our results suggest that a complete primary immunization schedule with the inactivated SARS-CoV-2 vaccine provides effective protection against severe COVID-19 disease for children 6-16 years. Funding: Agencia Nacional de Investigación y Desarrollo (ANID) Millennium Science Initiative Program and Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (FONDAP).

Facial fat necrosis after autologous fat transfer possibly associated with SARS-CoV-2 vaccine.

A 52-year-old female patient developed facial fat necrosis presenting with cutaneous induration three weeks after minimal access cranial suspension (MACS) lift with autologous fat grafting from the abdomen. Given that the patient received the Moderna SARS-CoV-2 vaccine one week after surgery, we hypothesize that the former predisposed her to tissue ischemia leading to fat necrosis. Histological findings after biopsy were consistent with fat necrosis, which included marked dermal fibrosis with areas of focal fat necrosis, lipophages, multinucleated giant cells, and siderophages. It is our hope that documenting this rare development in literature may serve as encouragement for adverse effect reporting after the SARS-CoV-2 vaccine administration and may boost inspection and monitoring of other health consequences by regulating agencies.

An evaluation of the safety and immunogenicity of MVC-COV1901: Results of an interim analysis of a phase III, parallel group, randomized, double-blind, active-controlled immunobridging study in Paraguay.

BACKGROUND: Data from previous studies of the MVC-COV1901 vaccine, a subunit vaccine against SARS-CoV-2 based on the stable prefusion spike protein (S-2P) adjuvanted with CpG 1018 adjuvant and aluminum hydroxide, suggest that the vaccine is generally safe and elicits a good immune response in healthy adults and adolescents. By comparing with AZD1222, this study adds to the findings from previous trials and further evaluates the breadth of protection offered by MVC-COV1901. METHODS: In this phase 3, parallel group, randomized, double-blind, active-controlled trial conducted in 2 sites in Paraguay, we assigned adults aged 18-91 years in a 1:1 ratio to receive intramuscular doses of MVC-COV1901 or AZD1222 administered as scheduled in the clinical trial. Serum samples were collected on the day of vaccination and 14 days after the second dose. Primary and secondary safety and immunogenicity endpoints were assessed. In addition, other outcomes investigated were cross-reactive immunity against the Omicron strain and the induction of IgG subclasses. RESULTS: A total of 1,030 participants underwent randomization. Safety data was derived from this set while primary immunogenicity data involved a per-protocol immunogenicity (PPI) subset including 225 participants. Among the participants, 58% are seropositive at baseline. When compared against AZD1222, MVC-COV1901 exhibited superiority in terms of neutralizing antibody titers and non-inferiority in terms of seroconversion rates. Reactogenicity was generally mild and no serious adverse event was attributable to MVC-COV1901. Both vaccines have a Th1-biased response predominated by the production of IgG1 and IgG3 subclasses. Omicron-neutralizing titers were 44.5 times lower compared to wildtype-neutralizing titers among seronegative individuals at baseline. This fold-reduction was 3.0 times among the seropositive. CONCLUSION: Safety and immunogenicity data of MVC-COV1901 from the study in Paraguay confirm previous results. The previous infection coupled with vaccination of this vaccine may offer protection against the Omicron strain though its durability is still unknown.

Protective Immunity of COVID-19 Vaccination with ChAdOx1 nCoV-19 Following Previous SARS-CoV-2 Infection: A Humoral and Cellular Investigation.

Infections caused by SARS-CoV-2 induce a severe acute respiratory syndrome called COVID-19 and have led to more than six million deaths worldwide. Vaccination is the most effective preventative measure, and cellular and humoral immunity is crucial to developing individual protection. Here, we aim to investigate hybrid immunity against SARS-CoV-2 triggered by the ChAadOx1 nCoV-19 vaccine in a Brazilian cohort. We investigated the immune response from ChAadOx1 nCoV-19 vaccination in naïve (noCOVID-19) and previously infected individuals (COVID-19) by analyzing levels of D-dimers, total IgG, neutralizing antibodies (Nabs), IFN-γ (interferon-γ) secretion, and immunophenotyping of memory lymphocytes. No significant differences in D-dimer levels were observed 7 or 15 days after vaccination (DAV). All vaccinated individuals presented higher levels of total IgG or Nabs with a positive correlation (R = 0.88). Individuals in the COVID-19 group showed higher levels of antibody and memory B cells, with a faster antibody response starting at 7 DAV compared to noCOVID-19 at 15 DAV. Further, ChAadOx1 nCoV-19 vaccination led to enhanced IFN-γ production (15 DAV) and an increase in activated T CD4+ naïve cells in noCOVID-19 individuals in contrast with COVID-19 individuals. Hence, our data support that hybrid immunity triggered by ChAadOx1 nCoV-19 vaccination is associated with enhanced humoral response, together with a balanced cellular response.

Immunogenicity, safety, and antiphospholipid antibodies after SARS-CoV-2 vaccine in patients with primary antiphospholipid syndrome.

OBJECTIVE: Coronavirus disease 19 (COVID-19) has an increased risk of coagulopathy with high frequency of antiphospholipid antibodies (aPL). Recent reports of thrombosis associated with adenovirus-based vaccines raised concern that SARS-CoV-2 immunization in primary antiphospholipid syndrome (PAPS) patients may trigger clotting complications. Our objectives were to assess immunogenicity, safety, and aPL production in PAPS patients, after vaccinating with Sinovac-CoronaVac, an inactivated virus vaccine against COVID-19. METHODS: This prospective controlled phase-4 study of PAPS patients and a control group (CG) consisted of a two-dose Sinovac-CoronaVac (D0/D28) and blood collection before vaccination (D0), at D28 and 6 weeks after second dose (D69) for immunogenicity/aPL levels. Outcomes were seroconversion (SC) rates of anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies (NAb) at D28/D69 in naïve participants. Safety and aPL production were also assessed. RESULTS: We included 44 PAPS patients (31 naïve) and 132 CG (108 naïve) with comparable age (p=0.982) and sex (p>0.999). At D69, both groups had high and comparable SC (83.9% vs. 93.5%, p=0.092), as well as NAb positivity (77.4% vs. 78.7%, p=0.440), and NAb-activity (64.3% vs. 60.9%, p=0.689). Thrombotic events up to 6 months or other moderate/severe side effects were not observed. PAPS patients remained with stable aPL levels throughout the study at D0 vs. D28 vs. D69: anticardiolipin (aCL) IgG (p=0.058) and IgM (p=0.091); anti-beta-2 glycoprotein I (aß2GPI) IgG (p=0.513) and IgM (p=0.468). CONCLUSION: We provided novel evidence that Sinovac-CoronaVac has high immunogenicity and safety profile in PAPS. Furthermore, Sinovac-CoronaVac did not trigger thrombosis nor induced changes in aPL production.

Description of Symptoms Caused by the Infection of the SARS-CoV-2 B.1.621 (Mu) Variant in Patients With Complete CoronaVac Vaccination Scheme: First Case Report From Santiago of Chile.

Vaccine administration is one of the most efficient ways to control the current coronavirus disease 2019 (COVID-19) pandemic. However, the appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants can avoid the immunity generated by vaccines. Thus, in patients with a complete vaccine schedule, the infection by SARS-CoV-2 may cause severe, mild, and asymptomatic manifestations of the disease. In this case report, we describe for the first time the clinical symptoms of four patients (three symptomatic; one asymptomatic) from Santiago of Chile, with a complete vaccination schedule with two doses of CoronaVac (Sinovac Life Science) infected with the variant of interest (VOI) B.1.621 (Mu). They were compared with four unvaccinated patients, who had a higher prevalence of symptoms after infection compared to vaccinated patients. In the CoronaVac-vaccinated group, an 80-year-old patient who registered various comorbidities required Invasive mechanical ventilation for 28 days with current home medical recovery discharge. By contrast, in the unvaccinated group, a 71-year-old presented more symptoms with more than 45 days of Invasive mechanical ventilation, which continues to date, presenting greater lung damage than the vaccinated hospitalized patient. This first report evidence differences in the clinical symptomatology of patients vaccinated and non-vaccinated infected with the VOI B.1.621 (Mu) and suggest the protective effects of CoronaVac against this variant.

Comparison of antibody response to SARS-CoV-2 after two doses of inactivated virus and BNT162b2 mRNA vaccines in kidney transplant.

BACKGROUND: Antibody response against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after mRNA or adenoviral vector-based vaccines is weak in kidney transplant (KT) patients. However, few studies have focused on humoral response after inactivated virus-based vaccines in KT. Here, we compare antibody response following vaccination with inactivated virus (CoronaVac®) and BNT162b2 mRNA. METHODS: A national multicentre cross-sectional study was conducted. The study group was composed of patients from all KT centres in Uruguay, vaccinated between 1 and 31 May 2021 (CoronaVac®, n = 245 and BNT162b2, n = 39). The control group was constituted of 82 healthy individuals. Participants had no prior confirmed coronavirus disease 2019 (COVID-19) test. Blood samples were collected between 30 and 40 days after the second dose. Serum-specific immunoglobulin G (IgG) antibodies against the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein were determined using the COVID-19 IgG QUANT ELISA Kit. RESULTS: Only 29% of KT recipients showed seroconversion (36.5% BNT162b2, 27.8% inactivated virus, P = 0.248) in comparison with 100% in healthy control with either vaccine. Antibody levels against RBD were higher with BNT162b mRNA than with inactivated virus [median (interquartile range) 173 (73-554) and 29 (11-70) binding antibody units (BAU)/mL, P < 0.034] in KT and 10 times lower than healthy control [inactivated virus: 308 (209-335) and BNT162b2: 2638 (2608-3808) BAU/mL, P < 0.034]. In multivariate analysis, variables associated with negative humoral response were age, triple immunosuppression, estimated glomerular filtration rate and time post-KT. CONCLUSION: Seroconversion was low in KT patients after vaccination with both platforms. Antibody levels against SARS-CoV-2 were lower with inactivated virus than BNT162b mRNA. These findings support the need for strategies to improve immunogenicity in KT recipients after two doses of either vaccine.

The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory.

Vaccines based on mRNA-containing lipid nanoparticles (LNPs) are a promising new platform used by two leading vaccines against coronavirus disease in 2019 (COVID-19). Clinical trials and ongoing vaccinations present with very high protection levels and varying degrees of side effects. However, the nature of the reported side effects remains poorly defined. Here we present evidence that LNPs used in many preclinical studies are highly inflammatory in mice. Intradermal injection of these LNPs led to rapid and robust inflammatory responses, characterized by massive neutrophil infiltration, activation of diverse inflammatory pathways, and production of various inflammatory cytokines and chemokines. The same dose of LNP delivered intranasally led to similar inflammatory responses in the lung and resulted in a high mortality rate. In summary, here we show that the LNPs used for many preclinical studies are highly inflammatory. Thus, their potent adjuvant activity and reported superiority comparing to other adjuvants in supporting the induction of adaptive immune responses likely stem from their inflammatory nature. Furthermore, the preclinical LNPs are similar to the ones used for human vaccines, which could also explain the observed side effects in humans using this platform.

SARS-CoV-2: previous coronaviruses, immune response, and development of vaccines.

Since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, when its characteristics were practically unknown, one aspect was evident: its high contagion rate. This high infection rate resulted in the spread of the virus in China, Europe, and, eventually, the rest of the world, including Mexico. At present, around 9 million people are infected, and around 470,000 have died worldwide. In this context, the need to generate protective immunity, and especially the generation of a vaccine that can protect the world population against infection in the shortest possible time, is a challenge that is being addressed in different countries using different strategies in multiple clinical trials. This opinion article will present the evidence of the induction of immune response in some of the viruses of the coronavirus family before COVID-19, such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus). The information collected about the induction of an immune response by SARS-CoV-2 will be presented, as well as a description of the vaccine candidates reported to date in the various ongoing clinical trials. Finally, an opinion based on the evidence presented will be issued on the potential success of developing vaccine prototypes.

Desde el surgimiento del nuevo coronavirus SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo severo) en China a finales del año 2019, cuando todavía era desconocido prácticamente en todos los aspectos, una característica era evidente: el alto índice de contagio entre la población. Esto resultó en la expansión del virus en China, Europa y, finalmente, en el resto del mundo, incluyendo México. Actualmente, alrededor de 9 millones de personas están infectadas, y han muerto cerca de 500,000 en todo el mundo. En este contexto, la necesidad de generar inmunidad protectora y, sobre todo, el desarrollo de una vacuna que pueda proteger a la población mundial contra la infección en el menor tiempo posible, es un reto que se está abordando en distintos países utilizando diversas estrategias en múltiples ensayos clínicos. En este artículo de opinión se presentan las evidencias de la inducción de respuesta inmunitaria con algunos de los virus de la familia de coronavirus previos al SARS-CoV-2, como el SARS-CoV (coronavirus del síndrome respiratorio agudo severo) y el MERS-CoV (síndrome respiratorio por coronavirus de Oriente Medio). Además, se presenta lo reportado hasta el momento acerca de la inducción de respuesta inmunitaria por el SARS-CoV-2, así como una descripción de los candidatos a vacunas informados hasta el momento en los distintos ensayos clínicos en curso. Finalmente se emite una opinión, basada en las evidencias presentadas, acerca del éxito potencial de los prototipos de vacunas en desarrollo.

SARS-CoV-2: previous coronaviruses, immune response, and development of vaccines / SARS-CoV-2: coronavirus previos, respuesta inmune y desarrollo de vacunas

Abstract Since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, when its characteristics were practically unknown, one aspect was evident: its high contagion rate. This high infection rate resulted in the spread of the virus in China, Europe, and, eventually, the rest of the world, including Mexico. At present, around 9 million people are infected, and around 470,000 have died worldwide. In this context, the need to generate protective immunity, and especially the generation of a vaccine that can protect the world population against infection in the shortest possible time, is a challenge that is being addressed in different countries using different strategies in multiple clinical trials. This opinion article will present the evidence of the induction of immune response in some of the viruses of the coronavirus family before COVID-19, such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus). The information collected about the induction of an immune response by SARS-CoV-2 will be presented, as well as a description of the vaccine candidates reported to date in the various ongoing clinical trials. Finally, an opinion based on the evidence presented will be issued on the potential success of developing vaccine prototypes.

Resumen Desde el surgimiento del nuevo coronavirus SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo severo) en China a finales del año 2019, cuando todavía era desconocido prácticamente en todos los aspectos, una característica era evidente: el alto índice de contagio entre la población. Esto resultó en la expansión del virus en China, Europa y, finalmente, en el resto del mundo, incluyendo México. Actualmente, alrededor de 9 millones de personas están infectadas, y han muerto cerca de 500,000 en todo el mundo. En este contexto, la necesidad de generar inmunidad protectora y, sobre todo, el desarrollo de una vacuna que pueda proteger a la población mundial contra la infección en el menor tiempo posible, es un reto que se está abordando en distintos países utilizando diversas estrategias en múltiples ensayos clínicos. En este artículo de opinión se presentan las evidencias de la inducción de respuesta inmunitaria con algunos de los virus de la familia de coronavirus previos al SARS-CoV-2, como el SARS-CoV (coronavirus del síndrome respiratorio agudo severo) y el MERS-CoV (síndrome respiratorio por coronavirus de Oriente Medio). Además, se presenta lo reportado hasta el momento acerca de la inducción de respuesta inmunitaria por el SARS-CoV-2, así como una descripción de los candidatos a vacunas informados hasta el momento en los distintos ensayos clínicos en curso. Finalmente se emite una opinión, basada en las evidencias presentadas, acerca del éxito potencial de los prototipos de vacunas en desarrollo.

Immunoinformatic construction of an adenovirus-based modular vaccine platform and its application in the design of a SARS-CoV-2 vaccine.

The current SARS-CoV-2 pandemic has imposed new challenges and demands for health systems, especially in the development of new vaccine strategies. Vaccines for many pathogens were developed based on the display of foreign epitopes in the variable regions of the human adenovirus (HAdV) major capsid proteins (hexon, penton and fiber). The humoral immune response against the HAdV major capsid proteins was demonstrated to play a role in the development of an immune response against the epitopes in display. Through the immunoinformatic profiling of the major capsid proteins of HAdVs from different species, we developed a modular concept that can be used in the development of vaccines based on HAdV vectors. Our data suggests that different immunomodulatory potentials can be observed in the conserved regions, present in the hexon and penton proteins, from different species. Using this modular approach, we developed a HAdV-5 based vaccine strategy for SARS-CoV-2, constructed through the display of SARS-CoV-2 epitopes indicated by our prediction analysis as immunologically relevant. The sequences of the HAdV vector major capsid proteins were also edited to enhance the IFN-gamma induction and antigen presenting cells activation. This is the first study proposing a modular HAdV platform developed to aid the design of new vaccines by inducing an immune response more suited for the epitopes in display.

Vacunas para SARS-CoV-2: diferentes estrategias de los desarrollos en curso / Vaccines for SARS-CoV-2: different strategies of ongoing developments

El objetivo de este artículo es proporcionar una guía que sirva para la interpretación y seguimiento de los esfuerzos que se están desarrollando en todo el mundo con el objetivo de obtener una vacuna que pueda generar inmunidad contra el nuevo coronavirus SARS-CoV-2 de 2019, el agente causante de la enfermedad por coronavirus denominada COVID-19. Cinco meses después de haber sido detectada la enfermedad, ya hay 102 vacunas en distintos estadios de desarrollo, registradas por la Organización Mundial de la Salud (OMS), correspondientes a 8 plataformas vacunales con diferentes estrategias, y todos los días aparecen nuevas. Esto representará un enorme desafío de organismos internacionales, para la evaluación, comparación y selección de aquellas que cumplan con los criterios regulatorios indispensables de seguridad y eficacia y que, por otro lado, puedan ser producidas en cantidades suficientes para abastecer la demanda mundial. (AU)

The objective of this article is to provide a guide to help the interpretation and monitoring the efforts that are being carried out worldwide to obtain a vaccine that will be able to generate immunity against the new 2019 SARS-CoV-2 coronavirus, the viral agent causes the disease named COVID-19. Five months after the disease was detected, there are already 102 vaccines at different stages of development, registered by World Health Organization (WHO), corresponding to 8 vaccination platforms base on different strategies, and every day new ones appear. This will represent a huge challenge for international organizations, to evaluate, compare and selects those that will meet the essential regulatory criteria of safety and efficacy and that, would be able to be produced in enough quantities to supply the worldwide demand. Key words: SARS-Cov-2 vaccine, vaccine platform, COVID-19 strategy, attenuated virus, viral vector, viral proteins, viral DNA, viral RNA, nucleic acids, viral like particles, WHO. (AU)