Non-replicating Viral Vectors Research Articles

Exploring the Potential of Gold Nanoparticle Technology and the Pan-Coronavirus Vaccine

When facing the threat of viral COVID-19 mutations, current objectives remain rooted in creating a universal vaccine, or a pan-coronavirus vaccine, that is effective against all COVID-19 variants. While most current COVID-19 vaccines use mRNA, nonreplicating viral vectors, inactivated vaccines, and protein subunits, nanotechnology is emerging as a viable resource for developing protective immunity against COVID-19. With the possibility of new COVID-19 variants emerging, increasing funds to further gold nanoparticle research is as crucial as technological innovation. This study hypothesizes that using a combination of “push” and “pull” methods to increase R&D incentives in gold nanoparticle research can take pan-coronavirus vaccine developments one step closer to boosting long-term immunization and universal applicability. This study's limitations include the immediacy of the COVID-19 pandemic and an inability to evaluate nanotechnology vaccinations after they have been put on the market. With its emphasis on funding gold nanotechnology research via “push” and “pull” incentives, this study’s implications include furthering global partnerships and contributing to the pan-coronavirus vaccine development with sensitivity to the rising risk of mutations and immunocompromised individuals.

COVID-19 inactivated and non-replicating viral vector vaccines induce regulatory training phenotype in human monocytes under epigenetic control.

Trained immunity is the enhanced innate immune response resulting from exposure to pathogens or vaccines against an unrelated pathogen stimulus. Certain vaccines induce a memory like response in monocytes and NK cells, leading to modulation in cytokine production, metabolic changes, and modifications in histone patterns. Here, we hypothesized that vaccination against SARS-CoV-2 could induce the training of monocytes in addition to stimulating the adaptive immune response. Therefore, we aimed to investigate the immunophenotyping, cytokine and metabolic profile of monocytes from individuals who were completely immunized with two doses of inactivated COVID-19 vaccine or non-replicating viral vector vaccine. Subsequently, we investigated the epigenetic mechanisms underlying monocyte immune training. As a model of inflammatorychallenge, to understand if the monocytes were trained by vaccination and how they were trained, cells were stimulated in vitro with the endotoxin LPS, an unrelated stimulus that would provoke the effects of training. When challenged in vitro, monocytes from vaccinated individuals produced less TNF-α and those who received inactivated vaccine produced less IL-6, whereas vaccination with non-replicating viral vector vaccine induced more IL-10. Inactivated vaccine increased classical monocyte frequency, and both groups showed higher CD163 expression, a hallmark of trained immunity. We observed increased expression of genes involved in glycolysis and reduced IRG1 expression in vaccinated subjects, a gene associated with the tolerance phenotype in monocytes. We observed that both vaccines reduced the chromatin accessibility of genes associated with the inflammatory response, the inactivated COVID-19 vaccine trained monocytes to a regulatory phenotype mediated by histone modifications in the IL6 and IL10 genes, while the non-replicating viral vector COVID-19 vaccine trained monocytes to a regulatory phenotype, mediated by histone modifications in the IL6, IL10, TNF, and CCL2 genes. Our findings support the recognized importance of adopting vaccination against SARS CoV-2, which has been shown to be effective in enhancing the adaptive immune response against the virus and reducing mortality and morbidity rates. Here, we provide evidence that vaccination also modulates the innate immune response by controlling the detrimental inflammatory response to unrelated pathogen stimulation.

Expanding Opportunities in Viral Oncolysis.

Expanding Opportunities in Viral Oncolysis.

An assessment of the strategy and status of COVID-19 vaccination in India.

The COVID-19 disease continues to cause devastation for almost 3years of its identification. India is one of the leading countries to set clinical trials, production, and administration of COVID-19 vaccination. Recent COVID-19 vaccine tracker record suggests that 12 vaccines are approved in India, including protein subunit, RNA/DNA, non-replicating viral vector, and inactivated vaccine. Along with that 16 more vaccines are undergoing clinical trials to counter COVID-19. The availability of different vaccines gives alternate and broad perspectives to fight against viral immune resistance and, thus, viruses escaping the immune system by mutations. Using the recently published literature on the Indian vaccine and clinical trial sites, we have reviewed the development, clinical evaluation, and registration of vaccines trial used in India against COVID-19. Moreover, we have also summarized the status of all approved vaccines in India, their associated registered clinical trials, manufacturing, efficacy, and their related safety and immunogenicity profile.

Preclinical development of a first-in-class vaccine encoding HER2, Brachyury and CD40L for antibody enhanced tumor eradication

The induction of antiviral innate immunity by systemic immunization with live virus can be employed to positively impact the response to therapeutic vaccination. We previously demonstrated that systemic immunization with a non-replicating MVA encoding CD40 ligand (CD40L) enhances innate immune cell activation and function, and triggers potent antitumor CD8+ T cell responses in different murine tumor models. Antitumor efficacy was increased when combined with tumor targeting antibodies. Here we report the development of TAEK-VAC-HerBy (TVH), a first-in-class human tumor antibody enhanced killing (TAEK) vaccine based on the non-replicating MVA-BN viral vector. It encodes the membrane bound form of human CD40L, HER2 and the transcription factor Brachyury. TVH is designed for therapeutic use in HER2- or Brachyury-expressing cancer patients in combination with tumor targeting antibodies. To preclude possible oncogenic activities in infected cells and to prevent binding of vaccine-encoded HER2 by monoclonal antibodies trastuzumab and pertuzumab, genetic modifications of HER2 were introduced in the vaccine. Brachyury was genetically modified to prevent nuclear localization of the protein thereby inhibiting its transcriptional activity. CD40L encoded in TVH enhanced human leukocyte activation and cytokine secretion in vitro. Lastly, TVH intravenous administration to non-human primates was proven immunogenic and safe in a repeat-dose toxicity study. Nonclinical data presented here highlight TVH as a first-in-class immunotherapeutic vaccine platform currently under clinical investigation.

COVID-19 vaccines adverse events: potential molecular mechanisms.

COVID-19 is an infectious disease caused by a single-stranded RNA (ssRNA) virus, known as SARS-CoV-2. The disease, since its first outbreak in Wuhan, China, in December 2019, has led to a global pandemic. The pharmaceutical industry has developed several vaccines, of different vector technologies, against the virus. Of note, among these vaccines, seven have been fully approved by WHO. However, despite the benefits of COVID-19 vaccination, some rare adverse effects have been reported and have been associated with the use of the vaccines developed against SARS-CoV-2, especially those based on mRNA and non-replicating viral vector technology. Rare adverse events reported include allergic and anaphylactic reactions, thrombosis and thrombocytopenia, myocarditis, Bell's palsy, transient myelitis, Guillen-Barre syndrome, recurrences of herpes-zoster, autoimmunity flares, epilepsy, and tachycardia. In this review, we discuss the potential molecular mechanisms leading to these rare adverse events of interest and we also attempt an association with the various vaccine components and platforms. A better understanding of the underlying mechanisms, according to which the vaccines cause side effects, in conjunction with the identification of the vaccine components and/or platforms that are responsible for these reactions, in terms of pharmacovigilance, could probably enable the improvement of future vaccines against COVID-19 and/or even other pathological conditions.

Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis.

Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules. Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model. In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons. Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted. PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.

Herpes Zoster Virus Reactivation in a 16 Year Old Female Post COVID-19 Vaccine. Case report and Review of the Literature

Background: According to WHO, there have been 9205 fatal COVID-19 cases confirmed in Saudi Arabia out of 793,729 cases overall (5). During the development of COVID-19 vaccines, several technologies were used including DNA-based, RNA-based vaccines, non-replicating viral vector vaccines, and inactivated vaccines. Objective: We present a case of varicella zoster virus reactivation post COVID-19 vaccine in a young medically free 16 years old female and review of the literature using the keywords “Herpes Zoster, “varicella zoster”,” shingles”, “post COVID-19 vaccine”, “Post COVID-19 cutaneous manifestations”. Methods: The search was conducted in Google Scholar, Scopus, PubMed, and Web of Science data bases. Results: We encountered 241 published studies in regard to post COVID-19 dermatologic manifestations including post COVID-19 vaccine herpes zoster reactivation in the English literature and one case in German. Our case and 4 other reported cases in the literature are patients aged of 20 years old and below. Conclusion: Varicella zoster virus falls under the family of Herpesviridae, It’s characterized by its ability to escape host immune system and remain dormant in ganglionic neurons. Reactivation of the infection will result in herpes zoster manifesting as painful vesicles in a dermatomal distribution. Possible link is the suppression of type-one interferons caused by the mRNA-based vaccine such as COVID-19 vaccines. Yet, potential correlation remains to be demonstrated.

The correlation between serum 25-hydroxy-vitamin D levels and anti-SARS-CoV-2 S-RBD IgG and neutralizing antibody levels among cancer patients receiving COVID-19 vaccines.

During the coronavirus disease 2019 (COVID-19) pandemic, vitamin D has been established as an immune-modulator that reduces pro-inflammatory damage which effectively diminish the severity of COVID-19. Vitamin D also has a significant effect against influenza and dengue and increase the seroconversion following influenza vaccination. To date, the role of vitamin D in optimizing the efficacy of COVID-19 vaccines remains unclear. This study aimed to analyze the correlation between serum 25-hydroxy-cholecalciferol or 25(OH)D levels and anti-SARS-CoV-2 S-RBD IgG and neutralizing antibody levels among cancer patients. A multicenter cross-sectional study was conducted among solid and hematologic cancer patients who were vaccinated with two doses of the same types of COVID-19 vaccines (either mRNA, non-replicating viral vector, or inactivated) within 6 months. The median serum 25(OH)D level in 119 cancer patients was 36.36 [IQR = 30.30] ng/mL. The seropositivity of S-RBD IgG and NAb reached 93.3 and 94.1%, respectively. The S-RBD IgG level was significantly higher in the sufficient group (median = 414.07 [1,441.83] AU/mL) than in the deficient group (median = 91.56 [652.00] AU/mL) (p-value = 0.049). Among non-chemotherapy subjects, the anti-SARS-CoV-2 S-RBD IgG levels had a significant positive correlation with 25(OH)D levels (p-value = 0.03; R = 0.588). The NAb levels also showed significantly positive correlation with 25(OH)D level (p-value = 0.005; R = 0.561). The 25(OH)D levels were positively correlated with S-RBD IgG levels among subjects younger than 60 years old (p-value = 0.047; R = 0.136). However, serum 25 (OH)D levels showed no such correlation with S-RBD IgG levels among subjects older than 60 years old (p-value = 0.933; R = 0.136). Both anti-SARS-CoV-2 S-RBD IgG and NAb levels developed moderate correlation with 25(OH)D levels among subjects treated without chemotherapy. The S-RBD IgG levels also had positive correlation with 25(OH)D levels among subjects younger than 60 years old. Thus, we recommended cancer patients to maintain serum 25(OH)D levels above 30 ng/mL (75 nmol/L) to enhance the efficacy of COVID-19 vaccines.

Comparison of three different COVID-19 vaccine platforms (CoronaVac, BTN162b2, and Ad5-nCoV) in individuals with and without prior COVID-19: Reactogenicity and neutralizing antibodies

Neutralizing antibodies (NAbs) can be indicators of collective immunity, vaccine efficacy, and the longevity of the humoral response. This study aimed to compare reactogenicity and NAbs generated by three different COVID-19 vaccine platforms in individuals with and without prior COVID-19. 336 individuals vaccinated (112 with CoronaVac [inactivated virus], 112 with BNT162b2 [messenger RNA], and 112 with Ad5-nCoV [non-replicating viral vector]) were included. NAbs were quantified with the cPass SARS-CoV-2 kit. Individuals immunized with the Ad5-nCoV showed higher reactogenicity than those immunized with the other vaccines (p < 0.001). The BTN162b2 vaccine-induced NAbs with higher inhibition capacity than the other platforms in the first dose. In individuals without prior COVID-19, the Ad5-nCoV vaccine generated lower NAbs against SARS-CoV-2 than those induced by two doses of the BTN162b2 (Ad5-nCoV 72.10 [55.6-93.4] vs. BTN162b2 98.41 [98.16-98.56], p < 0.0001). One individual did not generate NAbs (0.89%) after a complete immunization with CoronaVac; in BTN162b2, all generated these antibodies, and in the Ad5-nCoV group, four individuals (3.57%) did not generate NAbs. Comorbidities, gender, age, and reactogenicity did not significantly influence the generation of NAbs (p > 0.05); however, a history of COVID-19 before vaccination was associated with antibodies with greater neutralizing capacity after the first dose (p < 0.01). In conclusion, the mRNA vaccine (BTN162b2) had a remarkable better ability to produce NAbs and lower reactogenicity than the other platforms, whereas the Ad5-nCov vaccine induced the lowest NAbs response in individuals without a history of COVID-19; therefore, we suggest that a booster could benefit these individuals.

Advances in immunotherapy for glioblastoma multiforme.

Glioblastoma multiforme (GBM) is the most common and aggressive malignant brain tumor of the central nervous system and has a very poor prognosis. The current standard of care for patients with GBM involves surgical resection, radiotherapy, and chemotherapy. Unfortunately, conventional therapies have not resulted in significant improvements in the survival outcomes of patients with GBM; therefore, the overall mortality rate remains high. Immunotherapy is a type of cancer treatment that helps the immune system to fight cancer and has shown success in different types of aggressive cancers. Recently, healthcare providers have been actively investigating various immunotherapeutic approaches to treat GBM. We reviewed the most promising immunotherapy candidates for glioblastoma that have achieved encouraging results in clinical trials, focusing on immune checkpoint inhibitors, oncolytic viruses, nonreplicating viral vectors, and chimeric antigen receptor (CAR) immunotherapies.

Towards the development of an epitope-focused vaccine for SARS-CoV-2

The rapid spread of COVID-19 on all continents and the mortality induced by SARS-CoV-2 virus, the cause of the pandemic coronavirus disease 2019 (COVID-19) has motivated an unprecedented effort for vaccine development. Inactivated viruses as well as vaccines focused on the partial or total sequence of the Spike protein using different novel platforms such us RNA, DNA, proteins, and non-replicating viral vectors have been developed. The high global need for vaccines, now and in the future, and the emergence of new variants of concern still requires development of accessible vaccines that can be adapted according to the most prevalent variants in the respective regions.Here, we describe the immunogenic properties of a group of theoretically predicted RBD peptides to be used as the first step towards the development of an effective, safe and low-cost epitope-focused vaccine. One of the tested peptides named P5, proved to be safe and immunogenic. Subcutaneous administration of the peptide, formulated with alumina, induced high levels of specific IgG antibodies in mice and hamsters, as well as an increase of IFN-γ expression by CD8+ T cells in C57 and BALB/c mice upon in vitro stimulation with P5. Neutralizing titers of anti-P5 antibodies, however, were disappointingly low, a deficiency that we will attempt to resolve by the inclusion of additional immunogenic epitopes to P5. The safety and immunogenicity data reported in this study support the use of this peptide as a starting point for the design of an epitope restricted vaccine.

Advances in Research on COVID-19 Vaccination for People Living with HIV.

Advances in Research on COVID-19 Vaccination for People Living with HIV.

Potential COVID -19 Therapeutics in Clinical Trials – A Brief Review

The severe acute respiratory syndrome coronavirus 2 (SARS – CoV2), the causative viral pathogen of the COVID-19 pandemic belongs to the family of Coronaviruses which are positive single stranded RNA viruses. The scientific fraternity has developed and developing various types of vaccines for prevention against COVID-19, such as inactivated virus vaccines, mRNA vaccines, replicating vector protein subunit vaccines, etc., Out of which ten vaccines namely Novovax, Covovax (protein subunit vaccines), Pfizer BNT16b2, Moderna mRNA 1273 (mRNA vaccines), Johnson &amp; Johnson Ad26, Cov2.S, Astrazeneca AZD1222, Covishield (non-replicating viral vector vaccines), Covaxin, Sinopharm BBIBP-CorV, CoronoVac (inactivated vaccines) have been approved for clinical use by WHO. There is an urgent need for SARS-CoV2 specific therapeutics for the treatment of COVID-19 as there is the emergence of various variants such as Alpha, Beta, Gamma, Delta, Omicron, etc. The emergence of variants that possesses immune evading property and spike protein mutation have increased infectivity and more pathogenicity which impelled the need to develop various therapeutics for the treatment of COVID-19. This review compiles the information about potential antiviral candidates in preclinical trials intended for the treatment of COVID-19. The clinical development of such antivirals will be very crucial for the treatment of COVID-19 and also to curb the spread as the present scenario depends on the development of effective prophylactic vaccines.

Immunogenicity of SARS-CoV-2 vaccines in patients with cancer.

Transmission of the SARS-CoV-2 virus and its corresponding disease (COVID-19) has been shown to impose a higher burden on cancer patients than on the general population. Approved vaccines for use include new technology mRNA vaccines such as BNT162b2 (Pfizer–BioNTech) and mRNA-1273 (Moderna), and nonreplicating viral vector vaccines such as Ad26.COV2.S (Johnson & Johnson) and AZD1222 (AstraZeneca). Impaired or delayed humoral and diminished T-cell responses are evident in patients with cancer, especially in patients with haematological cancers or those under active chemotherapy. Herein we review the current data on vaccine immunogenicity in cancer patients, including recommendations for current practice and future research.

Case report of Guillain-Barré Syndrome after COVID BNT162b2 mRNA vaccine

IntroductionGuillain-Barré syndrome (GBS) is a rare immune disorder that affects peripheral nerves and the cause is not known completely, but it is associated with infections by viruses or bacteria. Case reportWe report the case of a 23-year-old male patient, a health student, who start 24 hours after received the second dose of COVID-19 vaccine, with proximal weakness of the right upper limb, later in the left side with descending and distal progression. DiscussionGBS cases related to COVID-19 vaccines have been published, the most common being BNT162b2, which is mRNA, there are also cases published after the AZD1222 (ChAdOx1) vaccine, which is a non-replicating viral vector. The incidence of GBS is estimated at 0.43 per 100.00 doses applied, under registered national incidence of 1.1-1.8 per 100,000 persons per year. ConclusionsIt is important to mention that although GBS can occur after vaccination against COVID-19, this incidence is much lower than which occurs in the community in Mexico associated with other diseases, considering more common the presence of cases related to infectious gastrointestinal diseases.

Reporte de caso de síndrome de Guillain-Barré posterior a la vacuna COVID BNT162b2 mRNA

Introduction: Guillain-Barré syndrome (GBS) is a rare immune disorder that affects peripheral nerves and the cause is not known completely, but it is associated with infections by viruses or bacteria.Case report: We report the case of a 23-year-old male patient, a health student, who start 24 hours after received the second dose of COVID-19 vaccine, with proximal weakness of the right upper limb, later on the left side with descending and distal progression.Discussion: GBS cases related to COVID-19 vaccines have been published, the most common being BNT162b2, which is mRNA, there are also cases published after the AZD1222 (ChAdOx1) vaccine, which is a non-replicating viral vector. The incidence of GBS is estimated at 0.43 per 100.00 doses applied, under registered national incidence of 1.1-1.8 per 100,000 persons per year.Conclusions: It is important to mention that although GBS can occur after vaccination against COVID-19, this incidence is much lower than which occurs in the community in Mexico associated with other diseases, considering more common the presence of cases related to infectious gastrointestinal diseases.

Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern

SummaryThe Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine has been widely deployed for COVID-19 vaccination programs in resource-limited settings. Here we confirm that neutralizing and binding antibody responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, when tested against multiple SARS-CoV-2 variants. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 4 to 5 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function, and neutralization. These high titer responses are of similar magnitude to humoral immune responses measured in convalescent donors who had been hospitalized with severe illness, and are cross-reactive against diverse SARS-CoV-2 variants, including the neutralization-resistant Omicron (B.1.1.529) variant that currently dominates global infections, as well as SARS-CoV-1. These data have implications for population immunity in areas where the Ad26.COV2.S vaccine has been widely deployed, but where ongoing infections continue to occur at high levels.

The human ACE-2 receptor binding domain of SARS-CoV-2 express on the viral surface of the Newcastle disease virus as a non-replicating viral vector vaccine candidate.

Since the SARS-CoV-2 infection was identified in December 2019, SARS-CoV-2 infection has rapidly spread worldwide and has become a significant pandemic disease. In addition, human death and serious health problem caused by SARS-CoV-2 infection, the socio-economic impact has been very serious. Here, we describe the development of the viral vector vaccine, which is the receptor-binding domain (RBD) of SARS-CoV-2 expressed on the surface of Newcastle disease virus (LVP-K1-RBD19). The RBD protein concentrations on the viral surface were measured by the sandwich ELISA method. 106.7 TCID50/ml of LVP-K1-RBD19 has a 0.17 μg of RBD protein. Optical density (OD) values of mouse sera inoculated with 10 μg of RBD protein expressed on the surface of LVP-K1-RBD19 generated 1.78-fold higher RBD-specific antibody titers than mice inoculated with 10 μg RBD protein with alum at 28 dpi. Moreover, mice inoculated with 10 μg of RBD protein expressed on the surface of LVP-K1-RBD19 virus showed more than 80% neutralization at 1:256 against the SARS-CoV-2 pseudovirus. These results demonstrated that inactivated LVP-K1-RBD19 virus produces neutralizing antibodies against SARS-CoV-2 in a short period and could be elect protective immunity in humans and LVP-K1-RBD19 will be a good candidate for the COVID-19 vaccine.

Immunogenicity induced by the use of alternative vaccine platforms to deal with vaccine shortages in a low- to middle-income country: Results of two randomized clinical trials

BackgroundShortages of component two of Sputnik V vaccine (rAd5) are delaying the possibility of achieving full immunisation. The immunogenic response associated with the use of alternative schemes to complete the scheme was not explored.MethodsWe did two non-inferiority randomized clinical trials with outcomes measures blinded to investigators on adults aged 21–65 years, vaccinated with a single dose of rAd26 ≥ 30 days before screening and no history of SARS-CoV-2. Participants were assigned (1:1:1:1:1) to receive either rAd5; ChAdOx1; rAd26; mRNA-1273 or BBIBP-CorV. The primary endpoint was the geometric mean ratio (GMR) of SARS-CoV-2 anti-spike IgG concentration at 28 days after the second dose, when comparing rAd26/rAd5 with rAd26/ChAdOx1, rAd26/rAd26, rAd26/mRNAmRNA-1273 and rAd26/BBIBP-CorV. Serum neutralizing capacity was evaluated using wild type SARS-CoV-2 reference strain 2019 B.1. The safety outcome was 28-day rate of serious adverse. The primary analysis included all participants who received ≥ 1 dose. The studies were registered with NCT04962906 and NCT05027672. Both trials were conducted in Buenos Aires, Argentina.FindingsBetween July 6 and August 3, 2021, 540 individuals (age 56·7 [SD 7·3]; 243 (45%) women) were randomly assigned to received rAd5 (n=150); ChAdOx1 (n=150); rAd26 (N=87); mRNAmRNA-1273 (n=87) or BBIBP-CorV (n=65). 524 participants completed the study. As compared with rAd26/rAd5 (1·00), the GMR (95%CI) at day 28 was 0·65 (0·51–0·84) among those who received ChAdOx1; 0·47 (0·34–0·66) in rAd5; 3·53 (2·68–4·65) in mRNA-1273 and 0·23 (0·16–0·33) in BBIBP-CorV. The geometric mean (IU/ml) from baseline to day 28 within each group increased significantly with ChAdOx1 (4·08 (3·07–5·43)); rAd26 (2·69 (1·76–4·11)); mRNA-1273 (21·98 (15·45–31·08)) but not in BBIBP-CorV (1·22 (0·80–1·87)).InterpretationExcept for mRNA-1273 which proved superior, in all other alternatives non-inferiority was rejected. Antibody concentration increased in all non-replicating viral vector and RNA platforms.FundingThe trials were supported (including funding, material support in the form of vaccines and testing supplies) by the Buenos Aires City Government.