In Commemoration of Dr. Farrokh Modabber: An Iranian Pioneer of Cellular Immunology, and Leishmaniases Vaccine Research in Iran and the World.

Born in 1940 in Rasht, Iran, Dr. Farrokh Modabber earned his B.A. in Bacteriology and Ph.D. in Microbiology from University of California, Los Angeles (UCLA). He joined the Harvard Medical School as a fellow before transitioning to a faculty role at Harvard School of Public Health (HSPH) and played a pivotal role in advancing Cellular Immunology. In the early 1970s, he returned to Iran as an Associate Professor at Pahlavi University in Shiraz. Subsequently, he rejoined HSPH before embarking on a tenure at Tehran University. As the head of the Pathobiology Department at Tehran University School of Public Health, he initiated the Tehran/Harvard joint M.Sc. program in Immunology, which played a crucial role in shaping the careers of numerous Iranian immunologists over the following decades. Dr. Modabber went on to hold esteemed positions such as Director General of the Pasteur Institute of Iran, visiting immunology lecturer at various universities, Coordinator of Research Capability Strengthening of WHO's Special Program for Research and Training in Tropical Diseases (TDR), Director of the Infectious Disease Research Institute (IDRI), and Senior Advisor of Drugs for Neglected Diseases initiative (DNDi), to name a few. This article highlights Dr. Modabber's impactful career, focusing on his efforts to combat global leishmaniasis.

Prevalence of hepatitis B, hepatitis C, and tuberculosis among people living with HIV in Iran: a systematic review and meta-analysis.

BACKGROUND: Up to now several studies estimate the prevalence of HBV, HCV, and TB among people living with HIV (PLWH) in Iran; however, their results are inconsistent. This study aimed to estimate the overall prevalence of HBV, HVC, and TB among Iranian PLWH. METHODS: In this systematic review and meta-analysis six databases including Medline, Web of Science, Scopus, MagIran, Scientific Information Database (SID), and Barakat Knowledge network system were searched up to October 2023 with no language restriction. All studies estimated the prevalence of HBV, HCV, and TB among PLWH in Iran were included. The random-effects model was used to report the study estimates. Results were reported at a 95% confidence interval (CI). RESULTS: Out of 1050 retrieved references, 58 articles met the eligibility criteria. Overall among PLWH, HBV prevalence was 13.0% (95% CI: 11.0, 15.0), HCV prevalence was 54% (95% CI: 45.0, 64.0), and TB prevalence was 19% (95% CI: 13.0, 24.0). The results from multivariate meta-regression analysis showed no statistically significant association between HBV and TB prevalence with the year of study, quality of studies, age, gender, and persons who inject drugs (PWID). HCV prevalence was significantly associated with PWID. CONCLUSION: We found HBV, HCV, and TB infections are common among PLWH in Iran and required to be screened and treated with effective and timely services.

Oropharyngeal tularemia outbreak linked to drinking contaminated tap water in North-Western Iran.

Tularemia is a widespread bacterial disease caused by Francisella tularensis. Iran is an endemic country for this zoonosis. In this report, we present a 2020 tularemia outbreak in a village in northwestern Iran involving 15 patients with the oropharyngeal form of the disease. This outbreak was probably linked to the consumption of contaminated drinking water.

Diversity of Rickettsia species in collected ticks from Southeast Iran.

Rickettsia occurs worldwide and rickettsiosis is recognized as an emerging infection in several parts of the world. Ticks are reservoir hosts for pathogenic Rickettsia species in humans and domestic animals. Most pathogenic Rickettsia species belong to the spotted Fever Group (SFG). This study aimed to identify and diagnose tick fauna and investigate the prevalence of Rickettsia spp. in ticks collected from domestic animals and dogs in the rural regions of Kerman Province, Southeast Iran. In this study, tick species (fauna) were identified and 2100 ticks (350 pooled samples) from two genera and species including Rhipicephalus linnaei (1128) and Hyalomma deteritum (972) were tested to detect Rickettsia genus using Real-time PCR. The presence of the Rickettsia genus was observed in 24.9% (95%CI 20.28-29.52) of the pooled samples. Sequencing and phylogenetic analyses revealed the presence of Rickettsia aeschlimannii (48.98%), Rickettsia conorii israelensis (28.57%), Rickettsia sibirica (20.41%), and Rickettsia helvetica (2.04%) in the positive samples. The results showed a significant association between county variables and the following variables: tick spp. (p < 0.001), Rickettsia genus infection in ticks (p < 0.001) and Rickettsia spp. (p < 0.001). In addition, there was a significant association between tick species and host animals (dogs and domestic animals) (p < 0.001), Rickettsia spp infection in ticks (p < 0.001), and Rickettsia spp. (p < 0.001). This study indicates a high prevalence of Rickettsia spp. (SFG) in ticks of domestic animals and dogs in rural areas of Kerman Province. The health system should be informed of the possibility of rickettsiosis and the circulating species of Rickettsia in these areas.

Detection of Various Rickettsial Species in Ticks Collected from Small Ruminants in Western Iran.

Background: Most of the rickettsioses are transmitted by ticks, and often overlooked by the medical profession, but are clinically important as they cause major human diseases. Recent studies have shown the existence of some rickettsial species in Iran, but very little information is available about the status of rickettsial epidemiology and ecology. This study investigated the presence of Rickettsia spp. in ticks and ruminants in western of Iran by molecular methods. Materials and Methods: 250 blood samples were collected from sheep and goats, as well as 244 ticks were collected opportunistically from ruminants in the Kurdistan province. The collected samples were tested using a real-time quantitative PCR (qPCR) assay targeting the Rickettsia 16SrRNA gene. Rickettsia spp. positive by the qPCR were further amplified by conventional PCR of the gltA and OmpA genes. These ampliqons were further analyzed by sequencing. Results: The ticks species collected in this study included Rhipicephalus sanguineus, Rh. turanicus, Haemaphysalis concinna, and Dermacentor marginatus. In total, DNA of Rickettsia spp. was detected in 131 collected ticks (53.7%). Of the positives, Rickettsia slovaca (59.2%) and Ri. hoogstraalii (16.3%) were the most common species identified followed by Ri. raoultii, Ri. massiliae, Ri. sibirica, and Ri. conorii subsp. israelensis. In contrast, there were no positives observed in the blood samples collected from ruminants. Conclusion: The results indicate the presence of rickettsial species in ticks. The detection of these pathogens is significant because they cause clinical disease in humans. The results support the notion that the Iranian public health system needs to be more aware of these diseases.

Intraspecific diversity of Meriones persicus (Rodentia; Gerbillinae), the main plague reservoir in Iran, and its connection to enzootic plague in Iran.

Plague, a lethal zoonotic disease, primarily circulates within rodent populations and their fleas. In Iran, the widely distributed jird, Meriones persicus, serves as the principal reservoir for plague, with a belief in the existence of five out of its six recognized subspecies within the country. However, these subspecies are classified into four mitochondrial cytochrome b sub-lineages (IA, IB, IIA, IIB). This discrepancy, combined with the presence of an unnamed sub-lineage in central Iran awaiting taxonomic clarification, has left intraspecific taxonomy unsettled and obscured the true alignment between mtDNA sub-lineages and nominal subspecies. In this study, we investigated the intraspecific variation in the cytb gene across populations sampled throughout Iran, focusing on underexplored regions between the Zagros and Alborz Mountains and central Iran. While our genetic data generally support reported subspecies validity in Iran, we raise questions about M. p. baptistae, emphasizing the need for further data from its type territory in Pakistan. Two main lineages of M. persicus (I and II) exhibit geographical isolation, with limited overlap in the central Zagros Mts., where three subspecies (M. p. ambrosius, M. p. rossicus, and M. p. persicus) coexist. Superimposing infected rodents' geographic coordinates onto updated sub-lineages' distribution revealed a potential association between sub-lineage IA (M. p. rossicus) and all enzootic plague cases from 1946 to 2023. M. persicus rossicus extends into the Caucasus (where plague infections are common), Eastern Turkey, and Iraq. Consequently, interpreting this finding in the context of plague surveillance in Iran and neighboring areas requires caution.

The Epidemiological Investigation of Yersinia pestis, Francisella tularensis, and Arenavirus Infections in Small Mammals in Northwestern Iran.

Background: The control and prevention of rodent-borne diseases are mainly based on our knowledge of ecology and the infectious status of their reservoir hosts. This study aimed to evaluate the prevalence of Francisella tularensis, Yersinia pestis, and arenavirus infections in small mammals and to assess the potential of disease occurrence in East Azerbaijan, northwest of Iran, in 2017 and 2018. Methods: Spleen and lung samples were obtained from all trapped small mammals. The real-time quantitative PCR (qPCR) method was used to detect nucleic acid sequences of F. tularensis, Y. pestis, and arenaviruses. Serum samples were tested for antibodies indicating the host response to F. tularensis and Y. pestis infections using the standard tube agglutination test and enzyme-linked immunosorbent assay (ELISA), respectively. Results: A total of 205 rodents, four Eulipotyphla, and one carnivore were captured. The most common rodent species captured (123 of 205 rodents, 60%) belonged to the genus Meriones (mainly Persian jird, Meriones persicus). In total, 317 fleas were removed from trapped animals. Flea species belonged to Xenopsylla buxtoni, Xenopsylla nuttalli, Stenoponia tripectinata, Paraceras melis, Ctenophthalmus rettigi smiti, Rhadinopsylla bivirgis, Paradoxopsyllus grenieri, and Nosopsyllus iranus. Using the qPCR tests, five spleen samples from M. persicus were positive for F. tularensis. The qPCR tests were negative for the detection of Y. pestis and arenaviruses. Finally, all serum samples tested were negative for antibodies against Y. pestis and F. tularensis. Conclusions: F. tularensis was the only zoonotic agent detected in rodents captured in East Azerbaijan. However, the diversity of trapped rodents and fleas provides the potential for the spread of various rodent-borne viral and bacterial diseases in the studied areas.

In Commemoration of Dr. Mostafa Pourtaghva Shahrestani, a Pioneer in Infectious Disease Research.

It is important to honor the contributions of scientific leaders who have dedicated their lives to advancing knowledge and serving their country. One way is to document their experiences and personalities in a documentary format, which can serve as a historical record and an inspiration for future generations. Dr. Mostafa Pourtaghva Shahrestani, a renowned physician and specialist in infectious diseases and tropical medicine, has made significant contributions to public health in Iran. He has played a crucial role in controlling infectious diseases such as smallpox, tuberculosis, rabies, plague, and cholera. Throughout his career, he has held various executive positions, including the head of Pasteur Hospital and the director of the Pasteur Institute of Iran. Dr. Pourtaghva's life is a testament to his unwavering dedication to public health services, as evidenced by his continuous effort, love, and interest in honest work. His inspiring story can serve as a model for those who seek to follow in his footsteps.

Molecular examination for Coxiella burnetii and Brucella spp. infections in Iranian women experiencing spontaneous miscarriage.

BACKGROUND: Spontaneous miscarriage, a leading health concern globally, often occurs due to various factors, including infections. Among these, Coxiella burnetii and Brucella spp. may have adverse effects on pregnancy outcomes. While previous research has established a link between infections and spontaneous miscarriage, our study aimed specifically to investigate the presence of these two pathogens in abortion samples from women who experienced spontaneous miscarriages in Iran. Our study can add to the existing knowledge by focusing on Iran, a region with a high prevalence of C. burnetii and Brucella spp. As a result, it could provide a better understanding and unique insights into the relationship of these pathogens with spontaneous miscarriages in endemic regions. METHODS: From March 2021 to March 2022, a total of 728 abortion samples (including placenta and cotyledon) were collected from 409 women who had experienced spontaneous miscarriages in the provinces of Tehran, Fars, and West Azerbaijan in Iran. The specimens included 467 Formalin-Fixed Paraffin-Embedded (FFPE) and 261 fresh frozen samples. After DNA extraction from abortion samples, the quantitative real-time PCR (qPCR) assay targeted a specific fragment of the IS1111 and IS711 elements for molecular identification of C. burnetii and Brucella spp., respectively. Furthermore, the qPCR assay employing specific primers for different species was used to determine the species of Brucella. RESULTS: Among the studied women, 1 out of 409 (0.24%) samples tested positive for Brucella spp., specifically Brucella melitensis. There were no positive specimens for C. burnetii. CONCLUSIONS: Our study contributes to understanding the potential involvement of Brucella species in spontaneous infectious abortion within endemic regions. The identification of B. melitensis in this study highlights the need for further research in this area. However, while our results suggest a relatively low or zero identification of these pathogens in our sample population, this does not rule out the possibility of undetected infections. Therefore, it is critical to acknowledge the limitations of the molecular techniques used (qPCR), which may have potential limitations such as sensitivity and specificity. Moreover, because 64.15% of our samples were FFPE, the sensitivity of the qPCR test may be reduced. These raise concerns about the accuracy of the reported prevalence rates and the potential for false positives or negatives.

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.

Rickettsia conorii subsp. israelensis infection in a pediatric patient presenting skin rash and abdominal pain: a case report from Southeast Iran.

BACKGROUND: The healthcare system in Iran appears to overlook Mediterranean spotted fever (MSF) as an endemic disease, particularly in pediatric cases, indicating the need for greater attention and awareness. CASE PRESENTATION: A six-year-old patient with fever, abdominal pain, headache, skin rashes, diarrhea, vomiting, and black eschar (tache noire) from southeast Iran was identified as a rickettsiosis caused by Rickettsia conorii subsp. israelensis through clinical and laboratory assessments, including IFA and real-time PCR. The patient was successfully treated with doxycycline. CONCLUSIONS: Symptoms like rash, edema, eschar, and abdominal pain may indicate the possibility of MSF during the assessment of acute febrile illness, IFA and real-time PCR are the primary diagnostic methods for this disease.

Role of Laboratory in Emerging Infectious Disease Control in Iran, Pasteur Institute of Iran, and national laboratory network.

Strengthening surveillance systems is a key aspect of outbreak response and was particularly important during the COVID-19 pandemic. Respiratory pathogens spread rapidly, and laboratory capacity is key to monitoring the spread. Prior to the pandemic, Iran had established a rapid response team and laboratory network to provide identification, monitoring, and detection of emerging infectious diseases, but did not have the laboratory capacity to respond to COVID-19. Following the announcement of the COVID-19 pandemic, the rapid response team diverted all attention to supporting COVID-19 surveillance. Iran built on the existing national laboratory infrastructure to incorporate SARS-CoV-2 surveillance into the response network. Based on existing international protocols, in-house molecular diagnosis capacity was operationalized, and commercial controls and assays were acquired and validated to national standards. The first COVID-19 laboratory was operational by January 25, less than 4 weeks before the initial detection of SARS-CoV-2 was announced. Assays and support were expanded and rolled out to form the COVID-19 National Laboratory Network, which consists of 560 multi-sectoral laboratories covering all provinces of Iran. The national laboratory network supports a wide range of operational capacities, including assay validation and protocol development, quality assurance, respiratory pathogen diagnosis and surveillance, and variant identification and assessment using multiple sequencing platforms. This network has supported the testing of over 55 million samples over the past 36 months using RT-qPCR and has sequenced approximately 2200 samples across the country, contributing the data to international databases, including GISAID.

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.

The surveillance of plague among rodents and dogs in Western Iran.

BACKGROUND: The causative agent of plague, Yersinia pestis, is maintained in nature via a flea-rodent cycle. Western Iran is an old focus for plague, and recent data indicate that rodents and dogs in this region have serological evidence of Y. pestis infection. The purpose of this study was to conduct a large-scale investigation of Y. pestis infection in shepherd dogs, rodents, and their fleas in old foci for plague in Western Iran. MATERIALS AND METHODS: This study was conducted in Hamadan province from 2014 to 2020. Rodents and fleas were collected from various locations throughout this region. Y. pestis was investigated in rodent spleen samples and fleas using culture, serology, and real-time PCR methods. Additionally, sera samples were collected from carnivores and hares in this region, and the IgG antibody against the Y. pestis F1 antigen was assessed using an ELISA. RESULTS: In this study, 927 rodents were captured, with Meriones spp. (91.8%) and Microtus qazvinensis (2.6%) being the most prevalent. A total of 6051 fleas were collected from rodents and carnivores, most of which were isolated from Meriones persicus. None of the rodents or fleas examined tested positive for Y. pestis using real-time PCR and culture methods. Meanwhile, IgG antibodies were detected in 0.32% of rodents. All serologically positive rodents belonged to M. persicus. Furthermore, none of the sera from the 138 carnivores (129 sheepdogs, five Vulpes vulpes, four Canis aureus), and nine hares tested positive in the ELISA test. CONCLUSION: This primary survey of rodent reservoirs shows serological evidence of Y. pestis infection. Western Iran is an endemic plague focus, and as such, it requires ongoing surveillance.

Genotyping and phylogenetic analysis of Coxiella burnetii in domestic ruminant and clinical samples in Iran: insights into Q fever epidemiology.

Coxiella burnetii, a zoonotic pathogen, is the causative agent of Q fever, an endemic disease in Iran. However, there is currently a lack of available data on the genotypes of C. burnetii in the country. Here, we typed 26 C. burnetii isolates detected in milk, abortion, cotylodon, and cardiac valve samples from various geographical areas and hosts (7 cattle, 8 goats, 10 sheep, and 1 human) using Multilocus Variable Number Tandem Repeat Analysis (MLVA/VNTR) with five loci:ms24, ms27, ms28, ms33, and ms34. As IS1111 was observed to be spontaneously inserted in locus ms23 across all of our examined C. burnetii samples, five loci were employed for MLVA/VNTR genotyping. Among the 26 C. burnetii strains, 22 distinct genotypes (A-V) were identified in the discriminative loci. In silico analysis categorized Iranian C. burnetii strains into five genomic groups along with seven singletons, representing 11 exiting clonal complexes worldwide. Clusters 10 and 11 exclusively consisted of Iranian samples. These findings revealed high genotyping diversity among C. burnetii isolates in Iran. The genotypes circulating in Iran differed significantly from those found in other regions worldwide. To gain a comprehensive understanding of Q fever epidemiology in Iran, it is crucial to conduct large-scale studies that assess the distribution of C. burnetii genotypes across different geographical areas, hosts, and sources.

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.

Molecular investigation of Coxiella burnetii and Francisella tularensis infection in ticks in northern, western, and northwestern Iran.

Tularemia and Q fever are endemic diseases in Iran; however, little information is available on the prevalence of the causative agents, Coxiella burnetii and Francisella tularensis, in Iranian ticks. This study investigated C. burnetii and F. tularensis among hard ticks in this country. We collected ticks from livestock and other mammals in Guilan, Mazandaran, Golestan (northern Iran), Kurdistan (western Iran), and West Azerbaijan (northwestern Iran) provinces. Genomic DNA from collected ticks was extracted and screened for C. burnetii and F. tularensis using Real-time PCR. A total of 4,197 ticks (belonging to 12 different species) were collected, and Ixodes ricinus (46.4%), Rhipicephalus turanicus (25%), and Rhipicephalus sanguineus sensu lato (19.1%) were the most collected species. Of 708 pooled tick samples, 11.3% and 7.20% were positive for C. burnetii and F. tularensis, respectively. The genus of Rhipicephalus had the highest (18.3%) C. burnetii infection among the collected tick pools (P<0.001). Furthermore, the most positive pools for F. tularensis belonged to Haemaphysalis spp. (44.4%). Kurdistan had the most significant percentage of C. burnetii-infected ticks (92.5%), and there was a meaningful relationship between the provinces and the infection (P< 0.001). The ticks from Golestan exhibited the highest F. tularensis infection rate (10. 9%), and the infection showed no significant relationship with the provinces (P = 0.19). Ticks collected from grasslands had a higher Coxiella burnetii infection rate than those collected from animals (39.4% vs. 7.9%; p<0.01). However, ticks collected from animal surfaces had a slightly higher rate of Francisella tularensis infection than those collected from grasslands (7.6% vs. 3.9%; p = 0.24). Here, we demonstrated the presence of both pathogens in the north (Guilan, Mazandaran, and Golestan provinces), the west (Kurdistan province), and the northwest (West Azerbaijan province) of Iran. The public health system should pay particular attention to tick bites in veterinary medicine and humans.

In Commemoration of Dr. Bijan Sadrizadeh, a Prominent Physician and Expert in the Field of Public Health in Iran and Around the World.

In line with the commemoration of the scientists who played a significant role in advancing knowledge and providing services to the country, it is imperative to publish their biographies so that their lives and achievements are recorded in the history of the country and serve as an example for future generations. Dr. Bijan Sadrizadeh, a physician and a public health specialist, undertook many valuable activities, particularly in the field of public health in Iran and the world during more than 60 years of great services, including the promotion of public health in the Islamic Republic of Iran, the development of I.R. Iran's international collaborations in the field of public health, and the development of research programs in the field of neglected tropical diseases and the eradication of polio in the world. He served the country in many high-level executive capacities, including three periods as deputy Minister of Health. In addition to several years of full-time employment in the World Health Organization (WHO), Dr. Sadrizadeh also served on the WHO Executive Board and was a member of numerous scientific and advisory committees. In reviewing his life, great determination, devotion, believing in primary health care and universal health coverage and a deep sense of responsibility are visible and can be an inspiration and a model for all.

Efficacy and Safety of a Protein-Based SARS-CoV-2 Vaccine: A Randomized Clinical Trial.

Importance: The protein-based SARS-CoV-2 vaccines FINLAY-FR-2 (Soberana 02) and FINLAY-FR-1A (Soberana Plus) showed good safety and immunogenicity in phase 1 and 2 trials, but the clinical efficacy of the vaccine remains unknown. Objective: To evaluate the efficacy and safety of a 2-dose regimen of FINLAY-FR-2 (cohort 1) and a 3-dose regimen of FINLAY-FR-2 with FINLAY-FR-1A (cohort 2) in Iranian adults. Design, Setting, and Participants: A multicenter, randomized, double-blind, placebo-controlled, phase 3 trial was conducted at 6 cities in cohort 1 and 2 cities in cohort 2. Participants included individuals aged 18 to 80 years without uncontrolled comorbidities, coagulation disorders, pregnancy or breastfeeding, recent immunoglobulin or immunosuppressive therapy, and clinical presentation or laboratory-confirmed COVID-19 on enrollment. The study was conducted from April 26 to September 25, 2021. Interventions: In cohort 1, 2 doses of FINLAY-FR-2 (n = 13 857) or placebo (n = 3462) were administered 28 days apart. In cohort 2, 2 doses of FINLAY-FR-2 plus 1 dose of FINLAY-FR-1A (n = 4340) or 3 placebo doses (n = 1081) were administered 28 days apart. Vaccinations were administered via intramuscular injection. Main Outcomes and Measures: The primary outcome was polymerase chain reaction-confirmed symptomatic COVID-19 infection at least 14 days after vaccination completion. Other outcomes were adverse events and severe COVID-19. Intention-to-treat analysis was performed. Results: In cohort 1 a total 17 319 individuals received 2 doses and in cohort 2 5521 received 3 doses of the vaccine or placebo. Cohort 1 comprised 60.1% men in the vaccine group and 59.1% men in the placebo group; cohort 2 included 59.8% men in the vaccine group and 59.9% in the placebo group. The mean (SD) age was 39.3 (11.9) years in cohort 1 and 39.7 (12.0) years in cohort 2, with no significant difference between the vaccine and placebo groups. The median follow-up time in cohort 1 was 100 (IQR, 96-106) days and, in cohort 2, 142 (137-148) days. In cohort 1, 461 (3.2%) cases of COVID-19 occurred in the vaccine group and 221 (6.1%) in the placebo group (vaccine efficacy: 49.7%; 95% CI, 40.8%-57.3%) vs 75 (1.6%) and 51 (4.3%) in cohort 2 (vaccine efficacy: 64.9%; 95% CI, 49.7%-59.5%). The incidence of serious adverse events was lower than 0.1%, with no vaccine-related deaths. Conclusions and Relevance: In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial of the efficacy and safety of FINLAY-FR-2 and FINLAY-FR-1A, 2 doses of FINLAY-FR-2 plus the third dose of FINLAY-FR-1A showed acceptable vaccine efficacy against symptomatic COVID-19 as well as COVID-19-related severe infections. Vaccination was generally safe and well tolerated. Therefore, Soberana may have utility as an option for mass vaccination of the population, especially in resource-limited settings, because of its storage condition and affordable price. Trial Registration: isrctn.org Identifier: IRCT20210303050558N1.

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.