Determination of COVID-19 Late Disorders as Possible Long-COVID and/or Vaccination Consequences.

In this era in which the vast majority of the global population have developed COVID-19 infection and/or got vaccinated against it, identification of the late disorders as the vaccines' side effect or long-COVID manifestation seems essential. This study included the vaccinated individuals of 4 different vaccine regimens including inactivated virus-based, subunit protein, and adenovirus-based vaccines in a follow-up schedule 6-month post the booster shot. All the documented vaccine adverse events were thoroughly assessed considering the cases' medical history by Adverse Events Committee of Pasteur Institute of Iran. Totally 329 individuals who got 3 doses of vaccination were followed 6 months after the booster shots among whom 41 (12.4%) cases with the mean age of 40.9 ± 10.48 years had a type of disorder. Gynecological and osteoarticular involvements were the most common recorded disorders of which 73.1% were possibly linked to vaccination outcomes and the rest were affected by both long-COVID-19 and vaccination. Notably, the average time of symptoms persistence was 155 ± 10.4 days. This study has the advantage of long-term follow-up which presents various forms of late events in each episode of COVID-19 infection and vaccination. About 26.8% of people with persistent complications suffered from both long-COVOD/ vaccination in whom the differentiation between the vaccine side effect and long-COVID manifestation was quite challenging. Long-term follow-up studies in large population seems essential to outline the role of long-COVID and vaccination regarding persistent complications.

Potential Protectivity of a Conjugated COVID-19 Vaccine against Tetanus.

PastoCovac is a subunit protein vaccine against COVID-19 which contains the tetanus toxoid as a carrier conjugated to SARS-CoV-2 RBD. The primary goal of the tetanus application was to elicit a stronger specific response in the individuals. However, conjugate vaccines have the potency to generate anticarrier antibodies in addition to the target antigen. Therefore, the present study aimed to evaluate the PastoCovac vaccine in the humoral immune induction against tetanus. Six groups of individuals, including those who received one, two, or three doses of the PastoCovac vaccine, Td vaccine, and also the controls who received other COVID-19 vaccines (except PastoCovac), were investigated. The anti-tetanus IgG was assessed by an ELISA assay in all vaccinated groups. The antibody persistency against tetanus in the group who received one dose of the PastoCovac vaccine was also assessed on day 60, 90, and 180 after the last injection. The anti-tetanus antibody titer in the three groups of PastoCovac recipients was positive, though additional doses of the vaccine led to a significant antibody rise (p = 0.003). Notably, the comparison of the mean antibody titer between the Td recipients and those who received one/two doses of PastoCovac showed that the mean rise in the antibody titer before and after the injection was not significant. Although the antibody titer on day 180 decreased to a lower level than on day 21, it was still estimated to be highly positive against tetanus. Eventually, none of the PastoCovac recipients presented vaccine side-effects during the follow-up. The current data indicate that the tetanus conjugate vaccine against COVID-19, PastoCovac, could induce immune responses against tetanus, which can persist for at least 6 months. Combination vaccine formulae containing TT and DT as carriers for conjugate vaccines could be considered instead of TT and/or DT boosters in adults if they are indicated.

The impact of ABO blood types on humoral immunity responses and antibody persistency after different COVID-19 vaccine regimens.

This study evaluated the possible effects of blood types on coronavirus disease (COVID-19) vaccine immunogenicity and antibody (Ab) persistency. Five different vaccinated groups against COVID-19 were investigated at Pasteur Institute of Iran from April 2021 to December 2022. Anti-Spike IgG and neutralizing Ab rise were tracked on Day 21 as well as the humoral immune persistency assessment 180 after booster shots. Late adverse events up to 6 months after the booster dose were collected. The results showed that blood type A, led to a significantly higher anti-Spike Ab rise in AstraZeneca primed recipients in comparison with Sinopharm primed ones in heterologous regimens (p: 0.019). Furthermore, blood type O was a great co-effector in homologous AstraZeneca recipients regarding neutralizing Ab rise (0.013). In addition, blood type O led to a better anti-Spike Ab persistency in the Sinopharm homologous group whereas type A had the best effect on neutralizing Ab durability in the same vaccine group. What is more, Rh-positive individuals in AstraZeneca + PastoCovac Plus group had a higher rate of anti-Spike Ab rise (p = 0.001). Neutralizing Ab rise was also induced in AstraZeneca homologous and heterologous regimens of Rh-positive individuals significantly higher than Sinopharm primed cases. The present study showed the potential impact of blood types A/O and Rh-positive on a better humoral immune responses and Ab persistency. It is proposed that blood type A and Rh-positive could increase the Ab rise in AstraZeneca vaccinated individuals. Moreover, blood type O might be a better co-effector of anti-Spike Ab persistency in Sinopharm recipients.

Long-term rheumatoid manifestations as a consequence of COVID-19 and/or vaccination: A case report after a 2-year follow-up.

COVID-19 is now established as a multi-organ involvement disease with a broad range of manifestations. Identification of post-acute COVID-19 incidence is critical according to increasing number of late symptoms reports. Hereby, we report a case with a past history of COVID-19 who presented different manifestations including osteoarticular and neurological involvement within a long-term follow-up. The organs involvement initiated lately after primary vaccinations (with inactivated vaccine) and lasted few months without any pre-existing medical condition. However, upon the completion of the vaccine schedule and receiving a protein subunit vaccine, PastoCovac Plus, as a booster, the symptoms improved substantially and resolved, though in the reinfection episode partial, reoccurrence was recorded. This presentation can be a challenging issue owing to the fact that the majority of global population are vaccinated and also experience COVID-19 in this era and sometimes differentiation between consequences of the virus as post COVID-19 or the vaccination side effects is difficult.

Lessons from COVID-19 Pandemic: A Successful Policy and Practice by Pasteur Institute of Iran.

The present study aims to provide an insight to the comprehensive efforts of Pasteur Institute of Iran (PII) regarding COVID-19 management, research, achievements, and vaccine production, though there are many challenges. The relevant literature review was investigated through national and international database and also reports from the related research departments. Six strategies were taken by PII to manage the pandemic of COVID-19. While this pandemic has been hopefully controlled, SARS-CoV-2 could still be a potential threat. Therefore, COVID-19 data management and updated studies, as well as long-term safety and efficacy of the SARS-CoV-2 vaccines are still on the agenda.

Immunogenicity and safety of heterologous boost immunization with PastoCovac Plus against COVID-19 in ChAdOx1-S or BBIBP-CorV primed individuals.

BACKGROUND: This study aimed at evaluation and comparison of PastoCovac Plus protein-subunit vaccine in parallel with ChAdOx1-S (AstraZeneca) and BBIBP-CorV (Sinopharm) in primarily vaccinated volunteers with two doses of ChAdOx1-S or BBIBP-CorV. MATERIALS AND METHODS: 194 volunteers enrolled the study who were previously primed with 2 doses of ChAdOx1-S or BBIBP-CorV vaccines. They were divided into two heterologous regimens receiving a third dose of PastoCovac Plus, and two parallel homologous groups receiving the third dose of BBIBP-CorV or ChAdOx1-S. Serum samples were obtained just before and 4 weeks after booster dose. Anti-spike IgG and neutralizing antibodies were quantified and the conventional live-virus neutralization titer, (cVNT50) assay was done against Omicron BA.5 variant. Moreover, the adverse events data were recorded after receiving booster doses. RESULTS: ChAdOx1-S/PastoCovac Plus group reached 73.0 units increase in anti-Spike IgG rise compared to the ChAdOx1-S/ ChAdOx1-S (P: 0.016). No significant difference was observed between the two groups regarding neutralizing antibody rise (P: 0.256), indicating equivalency of both booster types. Adjusting for baseline titers, the BBIBP-CorV/PastoCovac Plus group showed 135.2 units increase (P<0.0001) in anti-Spike IgG, and 3.1 (P: 0.008) unit increase in mean rise of neutralizing antibodies compared to the homologous group. Adjustment for COVID-19 history, age, underlying diseases, and baseline antibody titers increased the odds of anti-Spike IgG fourfold rise both in the ChAdOx1-S (OR: 1.9; P: 0.199) and BBIBP CorV (OR: 37.3; P< 0.0001) heterologous groups compared to their corresponding homologous arms. The odds of neutralizing antibody fourfold rise, after adjustment for the same variables, was 2.4 (P: 0.610) for the ChAdOx1-S heterologous group and 5.4 (P: 0.286) for the BBIBP CorV heterologous groups compared to their corresponding homologous groups. All the booster types had the potency to neutralize BA.5 variant with no significant difference. The highest rate of adverse event incidence was recorded for ChAdOx1-S homologous group. CONCLUSIONS: PastoCovac Plus booster application in primed individuals with BBIBP-CorV or ChAdOx1-S successfully increased specific antibodies' levels without any serious adverse events. This vaccine could be administrated in the heterologous regimen to effectively boost humoral immune responses.

A landscape on disorders following different COVID-19 vaccination: a systematic review of Iranian case reports.

There have been massive studies to develop an effective vaccine against SARS-CoV-2 which fortunately led to manage the recent pandemic, COVID-19. According to the quite rapidly developed vaccines in a fast window time, large investigations to assess the probable vaccine-related adverse events are crucially required. COVID-19 vaccines are available of different platforms and the primary clinical trials results presented acceptable safety profile of the approved vaccines. Nevertheless, the long-term assessment of the adverse events or rare conditions need to be investigated. The present systematic review, aimed at classification of probable vaccine-related unsolicited adverse events in Iranian population through the data collection of the published case report studies.The related published case reports were explored via PubMed, Web of Science and Google scholar according to the available published data up to 14th Dec, 2022 using PRISMA guideline. Out of 437 explored studies, the relevant data were fully investigated which totally led to 40 studies, including 64 case reports with a new onset of a problem post-vaccination. The cases were then classified according to the various items, such as the type of adverse event and COVID-19 vaccines.The reported COVID-19 vaccines in the studied cases included BBIBP-CorV, ChAdOx1-S, Sputnik V and COVAXIN. The results showed that the adverse events presented in 8 different categories, including cutaneous involvements in 43.7% (n = 28), neurologic problems (n = 16), blood/vessel involvement (n = 6), cardiovascular involvement (n = 5), ocular disorders (n = 4), liver disorder/failure (n = 2), graft rejection (n = 2) and one metabolic disorder. Notably, almost 60% of the cases had no comorbidities. Moreover, the obtained data revealed nearly half of the incidences occurred after the first dose of injection and the median duration of improvement after the symptom was 10 days (range: 2-120). In addition, 73% of all the cases were either significantly improved or fully recovered. Liver failure following ChAdOx1-S vaccination was the most serious vaccine adverse event which led to death in two individuals with no related medical history.Although the advantages of COVID-19 vaccination is undoubtedly significant, individuals including with a history of serious disease, comorbidities and immunodeficiency conditions should be vaccinated with the utmost caution. This study provides a comprehensive overview and clinical implications of possible vaccine-related adverse events which should be considered in further vaccination strategies. Nevertheless, there might be a bias regarding potential under-reporting and missing data of the case reports included in the present study. Although the reported data are not proven to be the direct vaccination outcomes and could be a possible immune response over stimulation, the people the population with a medium/high risk should be monitored after getting vaccinated against COVID-19 of any platforms. This could be achieved by a carefull attention to the subjects ' medical history and also through consulting with healthcare providers before vaccination.

Evaluation of PastoCovac plus vaccine as a booster dose on vaccinated individuals with inactivated COVID-19 vaccine.

COVID-19 pandemic has been managed through global vaccination programs. However, the antibody waning in various types of vaccines came to notice. Hereby, PastoCovac Plus as a protein subunit vaccine was investigated in immunized health care workers by COVAXIN (BBV152). The booster vaccine was recommended at least three months post the second dose of COVAXIN. Sera collection was done before and after each injection. SARS-CoV-2 PCR test was done monthly to detect any asymptomatic and symptomatic vaccine breakthrough. 47.9 and 24.3% of the participants were seronegative for anti-N and anti-S antibodies three months after the second dose of COVAXIN, respectively. On average, fold-rises of 70, 93, 8 and mean-rises of 23.32, 892.4, 5.59 were recorded regarding neutralizing antibody, quantitative and semi-quantitative anti-Spike antibody, respectively. Anti-Spike and neutralizing antibodies seroconversion was seen 59.3% and 45.7%, respectively. The vaccine breakthrough assessment showed that all the isolated samples belonged to SARS-CoV-2 Delta variant. PastoCovac Plus boosting is strongly recommended in combination with inactivated vaccine platforms against SARS-CoV-2.

A Comparative Study of Immunogenicity, Antibody Persistence, and Safety of Three Different COVID-19 Boosters between Individuals with Comorbidities and the Normal Population.

Data on immunogenicity, immune response persistency, and safety of COVID-19 boosters in patients with comorbidities are limited. Therefore, we aimed to evaluate three different boosters' immunogenicity and safety in individuals with at least one underlying disease (UD) (obesity, hypertension, and diabetes mellitus) with healthy ones (HC) who were primed with two doses of the BBIBP-CorV vaccine and received a booster shot of the same priming vaccine or protein subunit vaccines, PastoCovac Plus or PastoCovac. One hundred and forty subjects including sixty-three ones with a comorbidity and seventy-seven healthy ones were enrolled. The presence of SARS-CoV-2 antibodies was assessed before the booster injection and 28, 60, 90, and 180 days after it. Moreover, the adverse events (AEs) were recorded on days 7 and 21 postbooster shot for evaluating safety outcomes. Significantly increased titers of antispike, antiRBD, and neutralizing antibodies were observed in both UD and HC groups 28 days after the booster dose. Nevertheless, the titer of antispike IgG and anti-RBD IgG was lower in the UD group compared to the HC group. The long-term assessment regarding persistence of humoral immune responses showed that the induced antibodies were detectable up to 180 days postbooster shots though with a declined titer in both groups with no significant differences (p > 0.05). Furthermore, no significant difference in antibody levels was observed between each UD subgroup and the HC group, except for neutralizing antibodies in the hypertension subgroup. PastoCovac Plus and PastoCovac boosters induced a higher fold rise in antibodies in UD individuals than BBIBP-CorV booster recipients. No serious AEs after the booster injection were recorded. The overall incidence of AEs after the booster injection was higher in the UD group than the HC group among whom the highest systemic rate of AEs was seen in the BBIBP-CorV booster recipients. In conclusion, administration of COVID-19 boosters could similarly induce robust and persistent humoral immune responses in individuals with or without UD primarily vaccinated with two doses of the BBIBP-CorV. Protein-based boosters with higher a higher fold rise in antibodies and lower AEs in individuals with comorbidities might be considered a better choice for these individuals.

Assessment of long-term adverse events regarding different COVID-19 vaccine regimens within an 18-month follow-up study.

Early reports on coronavirus disease 2019 (COVID-19) vaccines presented the short-term adverse events (AEs). This follow-up study investigated a standard regimen based on protein subunit vaccines, PastoCovac and PastoCovac Plus, and the combinational vaccine regimens including AstraZeneca/PastoCovac Plus and Sinopharm/PastoCovac Plus. The participants were followed up to 6 months post the booster shot. All the AEs were collected through in-depth interviews using a valid researcher-made questionnaire and were evaluated regarding the association with the vaccines. Of the 509 individuals, 6.2% of the combinational vaccine participants had late AEs, of whom 3.3% suffered from cutaneous manifestations, followed by 1.1% arthralgia complaints, 1.1% with neurologic disorders, 0.3% ocular problems and 0.3% metabolic complications, with no significant difference between the vaccine regimens. For the standard regimen, 2% of the individuals experienced late AEs as (1%), neurological disorders (0.3%), metabolic problems (0.3%) and involvement of joints (0.3%). Notably, 75% of the AEs were persistent up to the end of the study. A low number of late AEs were captured in 18 months as 12 improbable, 5 unclassifiable, 4 possible and 3 probable associated AEs with the vaccine regimens. The benefits of COVID-19 vaccination far exceed the potential risks and late AEs seem to be uncommon.

PastoCovac and PastoCovac Plus as protein subunit COVID-19 vaccines led to great humoral immune responses in BBIP-CorV immunized individuals.

The optimal booster vaccine schedule against COVID-19 is still being explored. The present study aimed at assessment of the immunogenicity and antibody persistency of inactivated-virus based vaccine, BBIP-CorV and protein-subunit based vaccines, PastoCovac/Plus through heterologous and homologous prime-boost vaccination. Totally, 214 individuals who were previously primed with BBIBP-CorV vaccines were divided into three arms on their choice as heterologous regimens BBIBP-CorV/PastoCovac (n = 68), BBIBP-CorV/PastoCovac Plus (n = 72) and homologous BBIBP-CorV (n = 74). PastoCovac booster recipients achieved the highest rate of anti-Spike IgG titer rise with a fourfold rise in 50% of the group. Anti-RBD IgG and neutralizing antibody mean rise and fold rise were almost similar between the PastoCovac and PastoCovac Plus booster receivers. The antibody durability results indicated that the generated antibodies were persistent until day 180 in all three groups. Nevertheless, a higher rate of antibody titer was seen in the heterologous regimen compared to BBIP-CorV group. Furthermore, no serious adverse event was recorded. The protein subunit-based booster led to a stronger humoral immune response in comparison with the BBIP-CorV booster receivers. Both the protein subunit boosters neutralized SARS-CoV-2 significantly more than BBIP-CorV. Notably, PastoCovac protein subunit-based vaccine could be successfully applied as a booster with convenient immunogenicity and safety profile.

SARS-CoV-2 Viral Shedding and Associated Factors among COVID-19 Inpatients and Outpatients.

Background: According to the contagious ability of the new virus, SARS-CoV-2, characterization of viral shedding duration in the period of infection is highly valuable in terms of providing quarantine guidelines and isolation policies. Therefore, we aimed at viral shedding determination in 58 COVID-19 confirmed Iranian subjects in different stages. Methods: 58 COVID-19 confirmed Iranian subjects including 21 outpatients and 37 inpatients were investigated. The analytical data and clinical properties were documented in the standard questionnaire. The RT-PCR tests were done two and three weeks after the symptoms initiation. Results: Viral eradication occurred in 44.8% two weeks after illness initiation whereas in 71% who achieved a negative PCR test in the third week. Moreover, prolonged viral shedding was observed in hospitalized cases in comparison to outpatients. Almost 30% of patients continued viral shedding three weeks after disease initiation. Conclusion: A longer duration of viral shedding in hospitalized cases rather than outpatients was observed in this study. The results similar to other investigations call into question if the current policies are enough to prevent the viral spread or not. This study should be done on a larger sample to provide an appropriate time in isolation policy.

Characterization of long COVID-19 manifestations and its associated factors: A prospective cohort study from Iran.

The prevalence and variety complaints of COVID-19 cases in a long term have been investigated in recent studies. The symptoms over the time are various and unpredictable which may persist several weeks after full recovery. The importance of long-COVID-19 manifestations includes its effect on the recovered cases which requires a rational management based on an accurate guideline to handle post-acute COVID-19 state. The aim of this study was to evaluate the incidence of post-acute COVID-19 syndrome and to identify the associated risk factors as well as to compare new and persistent symptoms at different post-acute phases. Totally 254 individuals from Pasteur Institute of Iran (or/and their relatives) were investigated who had a previously confirmed COVID-19 PCR test. The long-term manifestations of the virus were categorized through a time window as acute, ongoing, post-COVID and persistent phases and the individuals were assessed by the face-to-face or the phone call interview according to their complaints. The data were then statistically analyzed to determine the frequency of the symptoms and also the associated factors in which a p value < 0.05 was considered significant. Except a small asymptotic group of five, 249 cases progressed the symptoms to acute phase among which 64.1% reported at least one symptom in post-acute phase. Neurological sequelae were found as the most frequent symptom (91.6%). Furthermore, there was a significant association between the underlying diseases, age and acute phase symptoms to the post-acute phase syndrome susceptibility (p < 0.05). In conclusion, the increasing number of the reports and studies on long COVID-19 which can hugely affect the life quality should be more investigated and explored in terms of the pathophysiology to achieve appropriate treatments in time. The clusters of symptoms, specially a combination of neurological signs, presenting over months after the recovery impose a huge difficulty to the recovered population.

Determination of Human Papillomavirus Type 18 Lineage of E6: A Population Study from Iran.

The epidemiological studies in Iran on HPV18 nucleotide changes are rare. This type of virus is prevalent in the Iranian population. Therefore, in the present study, we aimed to identify the genetic variability in HPV18 in the E6 region to evaluate the prevalence of lineage distribution and sublineages in a sample population in Iran. Overall, 60 HPV18 confirmed cases were investigated between 2019 and 2021. The specimens were collected, and molecular genotyping was done using the Linear Array HPV Genotyping Test. DNA extraction was performed by a viral DNA/RNA kit. The HPV E6 gene was amplified by using type-specific primers designed according to the HPV18 genome prototype sequence. The sequencing of the E6 region was successfully done on 43 samples which were then compared to the reference sequence. The most frequent sublineage of HPV18 in this study was A4 (69.7%), followed by A1 (18.6%) and A3 (11.6%). Neither A2 nor A5 sublineage was not detected in this study. The related nucleotide acid changes according to the main references were as follows: A3: T104C/T232G/T485C/C549A, A4: T104C/T485C/C549A. The predominance of A lineage with the high frequency of A4 sublineage was found in the present research. The importance of sublineages in susceptibility to a progressive form of infection requires to be more investigated among the different population.

SARS-CoV-2 re-infection rate in Iranian COVID-19 cases within one-year follow-up.

Since the COVID-19 pandemic initiation, the possibility of re-infection has been unclearly present. Although herd immunity has a potential reliance through natural infection, human corona viruses has the ability to subvert immunity and re-infection happens for seasonal corona viruses. Currently, the frequency of SARS-CoV-2 re-infection incidence is not exactly defined. In this study we aimed at determination of SARS-CoV-2 re-infection rate in Iranian population. In a total of 5696 COVID-19 suspicious individuals, RT-PCR was applied to diagnose the infection. The confirmed patients were followed for 12 months and serology tests were applied to measure the specific antibodies. Among 1492 confirmed COVID-19 cases, five individuals experienced the subsequent infection. The re-infection/reactivation incidence rate was totally 0.33% after one year of follow-up. The interval ranged from 63 to 156 days. All the cases had viral mutations in the second episode of the infection. All of them were symptomatic cases with moderate severity. The estimated rate of SARS-CoV-2 in Persian population is therefore rare and natural infection seems to induce good protection against re-infection which clarifies that mass vaccination can hugely affect the society.

SARS-CoV-2 presented moderately during two episodes of the infection with lack of antibody responses.

The world has gone through the critical phase of SARS-CoV-2 crisis caused by the new variants of the virus. The globally concerted effort to characterize viral genomic mutations across different clades has revealed several changes in the coding and also non-coding regions which might lead to a violent presentation or re-infection occurrence. Here, we studied a COVID-19 subject who represented the symptoms following the full recovery of the first infection. COVID-19 specific IgM and IgG were evaluated in both steps. The viral samples from oropharyngeal/nasopharyngeal were subjected to RT-PCR and full sequencing was done in both incidences. The sequencing data was fully investigated with the reference sequence of SARS-CoV-2 and the changes were detected. The obtained data is in favor of re-infection with 128 days of interval. SARS-CoV-2 presented more severely in the second episode of the disease and the specific antibodies against COVID-19 were not detectable. Both infections were caused by the same clade 20G, however, the mutation rates were higher in the second incidence including 10 nucleotide substitutions which had rarely been reported before. In the present study, the nucleotide mutations in various regions of the viral genome have been presented. The re-infection could have significant effect on clinical implications as well as vaccination.

Evaluation of transduced dendritic cells expressing HIV-1 p24-Nef antigens in HIV-specific cytotoxic T cells induction as a therapeutic candidate vaccine.

Various approaches have been investigated to prevent or eliminate HIV-1 since 1981. However, the virus has been affecting human population worldwide with no effective vaccine yet. The conserved regions among the viral genes are suitable targets in mutable viruses to induce the immune responses via an effective delivery platform. In this study, we aimed at evaluation of p24 and nef in two forms of full and truncated genes as two fusion antigenic forms according to our previous bioinformatics analysis. The designed antigens were then transferred through ex vivo generated dendritic cells and also proteins in BALB/c to assess and compare immunogenicity. p24 and Nef amino acid sequences were aligned, then, the most conserved regions were selected and two fusion forms as the truncated (p24:80-231aa-Nef:120-150aa) and the full from (p24-Nef) were cloned and expressed in prokaryotic and eukaryotic systems. Lentiviral vectors were applied to generate recombinant virions harboring the genes of interest to transduce generated murine dendritic cells. BALB/c mice received the recombinant DCs or recombinant proteins according to the defined schedule. IgG development was assessed to determine humoral immune activity and cellular immune responses were evaluated by IL-5 and IFN-y induction. Granzyme B secretion was also investigated to determine CTL activity in different immunized groups. The data showed high induction of cellular immune responses in dendritic cell immunization specifically in immunized mice with the truncated form of the p24 and Nef by high secretion of IFN-y and strong CTL activity. Moreover, protein/ DC prime-boost formulation led to stronger Th1 pathway and strong CTL activation in comparison with other formulations. The generated recombinant dendritic cells expressing p24-Nef induced humoral and cellular immunity in a Th1 pathway specifically with the in silico predicted truncated antigen which could be of high value as a dendritic cell therapeutic vaccine candidate against HIV-1.

Clinical characteristics of SARS-CoV-2 by re-infection vs. reactivation: a case series from Iran.

COVID-19 immunity in infected individuals may not be persistent. The specific response wanes in patients who have recovered from this infection. Nevertheless, it has not been fully understood whether true re-infection occurs or the viral reactivation. In this study, we investigated three COVID-19 patients who represented the symptoms after recovery. Chest CT scan was applied to assess the patients along with the viral samples from oropharyngeal/nasopharyngeal which were subjected to RT-PCR. The viral genome sequencing was applied where possible to distinguish possible re-infection or latent reactivation. Moreover, COVID-19-specific antibodies available data were evaluated in each incidence. The second episode of SARS-CoV-2 infection was different among the investigated subjects who experienced an interval between positive PCR tests ranged between 63 and 156 days. The disease presentation was less or more severe in the second infection. All cases were found IgG positive in the re-infection phase. The sequencing of SARS-CoV-2 sample obtained from two cases revealed a D614G mutation of S gene from the second isolated sample strengthens the case for the re-infection. The possibility of re-infection and reactivation could have significant effect on clinical implications and also vaccination. Our data supports clear warning of SARS-CoV-2 continuous circulation potency among the populations in spite of herd immunity either with natural infection or vaccination. This issue is critical in term of the patients, clinical investigate, and viral transmission.

Prolonged viral shedding and antibody persistence in patients with COVID-19.

SARS-CoV-2 as a new global threat has affected global population for one year. Despite the great effort to eradicate this infection, there are still some challenges including different viral presentation, temporal immunity in infected individuals and variable data of viral shedding. We studied 255 COVID-19 suspected individuals to assess the viral shedding duration and also the antibody development against SARS-CoV-2 among the cases. Real Time RT-PCR assay was applied to determine the virus presence and SARS-CoV-2 antibodies were evaluated using SARS-CoV-2 IgM and IgG kits. 113 patients were confirmed for COVID-19 infection. The patients were followed until negative PCR achieved. The median viral shedding among studied population was obtained 34.16 (±17.65) days which was not significantly associated with age, sex and underlying diseases. Shiver and body pain were found in prolonged form of the infection and also patients who had gastrointestinal problems experienced longer viral shedding. Moreover, IgG was present in 84% of patients after 150 days. According to this data, the median viral shedding prolongation was 34.16 days which indicates that 14 days isolation might not be enough for population. In addition, IgG profiling indicated that it is persistent in a majority of patients for nearly 6 months which has brought some hopes in vaccine efficacy and application.

Bioinformatics Analysis of SARS-CoV-2 to Approach an Effective Vaccine Candidate Against COVID-19.

The emerging Coronavirus Disease 2019 (COVID-19) pandemic has posed a serious threat to the public health worldwide, demanding urgent vaccine provide. According to the virus feature as an RNA virus, a high rate of mutations imposes some vaccine design difficulties. Bioinformatics tools have been widely used to make advantage of conserved regions as well as immunogenicity. In this study, we aimed at immunoinformatic evaluation of SARS-CoV-2 proteins conservancy and immunogenicity to design a preventive vaccine candidate. Spike, Membrane and Nucleocapsid amino acid sequences were obtained, and four possible fusion proteins were assessed and compared in terms of structural features and immunogenicity, and population coverage. MHC-I and MHC-II T-cell epitopes, the linear and conformational B-cell epitopes were evaluated. Among the predicted models, the truncated form of Spike in fusion with M and N protein applying AAY linker has high rate of MHC-I and MCH-II epitopes with high antigenicity and acceptable population coverage of 82.95% in Iran and 92.51% in Europe. The in silico study provided truncated Spike-M-N SARS-CoV-2 as a potential preventive vaccine candidate for further in vivo evaluation.