A Comparison of the Immunogenicity and Safety of an Additional Heterologous versus Homologous COVID-19 Vaccination among Non-Seroconverted Immunocompromised Patients after a Two-Dose Primary Series of mRNA Vaccination: A Systematic Review and Meta-Analysis.

This systematic review and meta-analysis aimed to compare the immunogenicity and safety of an additional heterologous (viral vector) versus homologous (mRNA) COVID-19 vaccine dose among non-seroconverted immunocompromised patients after a two-dose primary series of mRNA vaccine. We searched studies published up to 21 June 2023 in PubMed, Scopus, and Embase. The meta-analysis was conducted to compare the seropositivity rates based on anti-SARS-CoV-2 spike protein IgG (anti-S IgG) and SARS-CoV-2-specific T-cell immune response rates, assessed by interferon-γ release assay at 4 weeks, and the incidences of serious adverse events (SAEs) within 28 days between the two vaccine regimens. In four included randomized controlled trials (RCTs), there were no statistically significant differences in the seropositive rate of anti-S IgG (risk ratio [RR]: 0.79, 95% CI: 0.48-1.29) and the concentration of SARS-CoV-2 interferon-γ (RR: 1.19, 95% CI: 0.96-1.48) between heterologous and homologous regimens. The heterologous regimen exhibited a significantly lower incidence of injection pain (RR: 0.55, 95% CI: 0.45-0.69), but a higher incidence of headache (RR: 1.44, 95% CI: 1.02-2.02) compared with the homologous regimen. No vaccine-related SAEs were reported within 28 days following vaccination. An additional heterologous or homologous COVID-19 vaccine dose was well tolerated and demonstrated a comparable vaccine immunogenicity among non-seroconverted immunocompromised patients who were initially vaccinated with a two-dose COVID-19 mRNA vaccine. This finding supports the recommendations of an extended primary series of COVID-19 vaccination in immunocompromised persons.

Duration of Immunity in Cattle to Lumpy Skin Disease Utilizing a Sheep Pox Vaccine.

The transmission of lumpy skin disease (LSD) occurs through ticks, mosquitoes, and flies. The most effective way to combat LSD is to conduct large-scale vaccination, covering the entire cattle population with safe and effective vaccines, while introducing restrictions on the movement of livestock. The first and only LSD cases that occurred in Armenia happened in 2015,and they were controlled with the use of a once yearly heterologous sheep pox vaccine for cattle in high-risk areas. We have previously reported on the safety and immunogenicity of this vaccine in cattle, but information on the duration of immunity is lacking. Our aim was to determine the duration of immunity to the LSD virus (LSDV) in cattle when utilizing a heterologous sheep pox vaccine. We have evaluated antibodies in cattle blood prior to and post-vaccination (1, 6, and 11 months). We have utilized an enzyme-linked immunosorbent assay to follow the development and waning of LSDV antibodies in vaccinated cattle in two age groups: 1) young unvaccinated cattle ≤12 months of age and 2) adult cattle that had previously been vaccinated. Our results were consistent with our previous study in Armenia, showing a high level of population immunity, 80.0-83.3%, in both age groups at 1 month, with a significant (p = 0.001) drop for young cattle at 6 months. Previously vaccinated adult cattle showed a longer duration of immunity at 11 months for this heterologous sheep pox vaccine. Based on these data, we advise that young cattle receive an additional booster vaccination 4-6 months after their first vaccination, and then yearly vaccinations in high-risk areas.

Boosting Vaccine Response in Autoimmune Rheumatic Disease Patients With Inadequate Seroconversion: An Analysis of the Immunogenicity of Vector-Based and Inactivated Vaccines.

BACKGROUND: An additional dose of COVID-19 vaccine is being offered to vaccinated people, especially those immunocompromised. The most widely available vaccines in India are the adenoviral vector-based AZD1222 (ChAdOx1 nCoV-19) and the heat-inactivated (BBV152). This study investigated the efficacy of both vaccines in patients with autoimmune rheumatic diseases (AIRD). OBJECTIVES:  To compare final anti-SARS-CoV-2 antibody titers, neutralization of pseudovirions by these antibodies, and T cell responses between patients of AIRD who had received the third dose of AZD1222 and BBV152 vaccines. METHODS: Patients with stable AIRD who had completed two doses of COVID-19 vaccination but had a suboptimal response (anti-receptor binding domain (RBD) antibody<212) were randomized (1:1) to receive either AZD1222 or BBV152 as a booster dose. Patients with previous hybrid immunity or those who developed COVID-19 during the trial were excluded. Antibody titers, neutralization of Wuhan and Omicron pseudovirions, and interferon release by T cells (enzyme-linked immunosorbent spot (ELISpot)) in response to the Spike antigen were measured four weeks after this booster dose. RESULTS: 146 were screened, 91 were randomized, and 67 were analyzed per protocol. The third dose improved antibody titers (p<0.001), neutralization of the Wuhan strain (p<0.001), and T cell interferon release (p<0.001) but not neutralization of the Omicron strain (p=0.24). Antibody titers were higher (p<0.005) after ADZ1222 boost (2,414 IU (interquartile range (IQR): 330-10,315)) than BBV1222 (347.7 IU (0.4-973)). Neutralization of the Wuhan stain was better (AZD1222: 76.6%(23.0-95.45) versus BBV152 (32.7% (0-78.9), p=0.03 by ANCOVA). Neutralization of Omicron (0 (0-28.4) vs 0 (0-4.8)) and T cell interferon release (57.0 IU (23.5-95) vs 50.5 IU (13.2-139)) were similar. CONCLUSION: The third dose improved all parameters of immunogenicity in AIRD patients with previous inadequate responses except Omicron neutralization. The vector-based vaccine exhibits notable efficacy, particularly in antibody titers and neutralizing the Wuhan strain. TRIAL REGISTRATION: CTRI/2021/12/038928.

Durability of the Effectiveness of Heterologous COVID-19 Vaccine Regimens in Thailand: Retrospective Cohort Study Using National Registration Data.

BACKGROUND: The durability of heterologous COVID-19 vaccine effectiveness (VE) has been primarily studied in high-income countries, while evaluation of heterologous vaccine policies in low- and middle-income countries remains limited. OBJECTIVE: We aimed to evaluate the duration during which the VE of heterologous COVID-19 vaccine regimens in mitigating serious outcomes, specifically severe COVID-19 and death following hospitalization with COVID-19, remains over 50%. METHODS: We formed a dynamic cohort by linking records of Thai citizens aged ≥18 years from citizen vital, COVID-19 vaccine, and COVID-19 cases registry databases between May 2021 and July 2022. Encrypted citizen identification numbers were used to merge the data between the databases. This study focuses on 8 common heterologous vaccine sequences: CoronaVac/ChAdOx1, ChAdOx1/BNT162b2, CoronaVac/CoronaVac/ChAdOx1, CoronaVac/ChAdOx1/ChAdOx1, CoronaVac/ChAdOx1/BNT162b2, BBIBP-CorV/BBIBP-CorV/BNT162b2, ChAdOx1/ChAdOx1/BNT162b2, and ChAdOx1/ChAdOx1/mRNA-1273. Nonimmunized individuals were considered for comparisons. The cohort was stratified according to the vaccination status, age, sex, province location, month of vaccination, and outcome. Data analysis employed logistic regression to determine the VE, accounting for potential confounders and durability over time, with data observed over a follow-up period of 7 months. RESULTS: This study includes 52,580,841 individuals, with approximately 17,907,215 and 17,190,975 receiving 2- and 3-dose common heterologous vaccines (not mutually exclusive), respectively. The 2-dose heterologous vaccinations offered approximately 50% VE against severe COVID-19 and death following hospitalization with COVID-19 for 2 months; however, the protection significantly declined over time. The 3-dose heterologous vaccinations sustained over 50% VE against both outcomes for at least 8 months, as determined by logistic regression with durability time-interaction modeling. The vaccine sequence consisting of CoronaVac/CoronaVac/ChAdOx1 demonstrated >80% VE against both outcomes, with no evidence of VE waning. The final monthly measured VE of CoronaVac/CoronaVac/ChAdOx1 against severe COVID-19 and death following hospitalization at 7 months after the last dose was 82% (95% CI 80.3%-84%) and 86.3% (95% CI 83.6%-84%), respectively. CONCLUSIONS: In Thailand, within a 7-month observation period, the 2-dose regimens could not maintain a 50% VE against severe and fatal COVID-19 for over 2 months, but all of the 3-dose regimens did. The CoronaVac/CoronaVac/ChAdOx1 regimen showed the best protective effect against severe and fatal COVID-19. The estimated durability of 50% VE for at least 8 months across all 3-dose heterologous COVID-19 vaccine regimens supports the adoption of heterologous prime-boost vaccination strategies, with a primary series of inactivated virus vaccine and boosting with either a viral vector or an mRNA vaccine, to prevent similar pandemics in low- and middle-income countries.

Comparative Safety and Effectiveness of Heterologous CoronaVac-ChAdOx1 versus Homologous CoronaVac Vaccination in a Real-World Setting: A Retrospective Cohort Study.

Background: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has outpaced vaccine availability and delivery from vaccine manufacturers, and thus, a scarcity of vaccines happened to many countries around the world. In Thailand, the mixing of different types of vaccines was approved and clinically implemented partially due to concerns about the availability and efficacy of one vaccine. Objective: This study aimed to investigate the effectiveness and safety of heterologous CoronaVac-ChAdOx1 nCoV-19 vaccines compared with the usual regimen of homologous CoronaVac-CoronaVac. A retrospective cohort study was conducted by dividing patients into the CoronaVac-CoronaVac group and the CoronaVac-ChAdOx1 group. Results: A total of 875 patients received vaccinations at Srisangwan Hospital between April to October 2021 and were included for analysis. The patients in both homologous and heterologous groups had low rates of COVID-19 infection. In addition, the hospitalization rates in the 40 days after the second vaccination were low in both regimens. Minimal adverse events (AE) were reported in both groups, including local AE (e.g., discomfort at the injection site, rash, soreness, swelling, and redness) and systemic AE (e.g., fever, headache, weariness, nausea, vomiting, diarrhoea, and myalgia). Moreover, several factors were associated with lower adverse events following immunization (AEFIs), including age ≥ 50 years, male, and body weight ≥ 50 kg. In contrast, thyroid disease, diabetes mellitus, allergic rhinitis, and psychiatric disorders were independent risk factors associated with an increase in AEFIs. Conclusions: The heterologous CoronaVac-ChAdOx1 and homologous CoronaVac-CoronaVac regimens were promising vaccination strategies for the prevention of SARS-CoV-2 infection. However, the heterologous CoronaVac-ChAdOx1 potentially caused fewer AEFIs compared with the homologous CoronaVac-CoronaVac regimen.

Concurrent administration of COVID-19 and influenza vaccines enhances Spike-specific antibody responses.

The bivalent COVID-19 mRNA boosters became available in fall 2022 and were recommended alongside the seasonal influenza vaccine. However, the immunogenicity of concurrent versus separate administration of these vaccines remains unclear. Here, we analyzed antibody responses in healthcare workers who received the bivalent COVID-19 booster and the influenza vaccine on the same day or different days. IgG1 responses to SARS-CoV-2 Spike were higher at peak immunogenicity and 6 months following concurrent administration compared with separate administration of the COVID-19 and influenza vaccines. These data suggest that concurrent administration of these vaccines may yield higher and more durable SARS-CoV-2 antibody responses.

Breakthrough SARS-CoV-2 Omicron Variant in Individuals Primed with Heterologous Vaccines Enhances Inhibition Performance of Neutralizing Antibody to BA.2 Parental Lineage.

This study aims to analyze the neutralization ability against Omicron parental variants in five clusters of individuals with different Coronavirus disease (COVID-19) immunity backgrounds, including individuals receiving a homologous or heterologous vaccine without prior infection, recovered patients with homologous or heterologous vaccination, and recovery patients without vaccination. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surrogate virus neutralization assay was performed on serum samples. Spearman correlation analysis showed that the percent inhibition against Omicron B.1.1.529 and BA.2 was significantly related to the period of serum collection (r = 0.730 and 0.787, p < 0.001, respectively). Very strong correlation between percent inhibition of neutralizing antibody against Omicron B.1.1.529 and BA.2 variants (rs = 0.973, p < 0.001) was also observed. The neutralizing activity of the sera from recovery patients receiving homologous and heterologous vaccine against the wild-type, B.1.1.529, and BA.2 Omicron variants was significantly higher (p < 0.001) than that of recovery patients without vaccination. This study robustly showed that the breakthrough SARS-CoV-2 Omicron variant in individuals who received homologous and heterologous vaccines had a high level of neutralizing activity against B.1.1.529 and BA.2 parental lineage of XBB subvariants. Therefore, the next-generation COVID-19 vaccine against emerging variants is needed to improve resilience against ongoing variants, particularly for persons who have never been infected.

A third vaccine dose equalises the levels of effectiveness and immunogenicity of heterologous or homologous COVID-19 vaccine regimens, Lyon, France, December 2021 to March 2022.

BackgroundTo cope with the persistence of the COVID-19 epidemic and the decrease in antibody levels following vaccination, a third dose of vaccine has been recommended in the general population. However, several vaccine regimens had been used initially for the primary vaccination course, and the heterologous Vaxzevria/Comirnaty regimen had shown better efficacy and immunogenicity than the homologous Comirnaty/Comirnaty regimen.AimWe wanted to determine if this benefit was retained after a third dose of an mRNA vaccine.MethodsWe combined an observational epidemiological study of SARS-CoV-2 infections among vaccinated healthcare workers at the University Hospital of Lyon, France, with a prospective cohort study to analyse immunological parameters before and after the third mRNA vaccine dose.ResultsFollowing the second vaccine dose, heterologous vaccination regimens were more protective against infection than homologous regimens (adjusted hazard ratio (HR) = 1.88; 95% confidence interval (CI): 1.18-3.00; p = 0.008), but this was no longer the case after the third dose (adjusted HR = 0.86; 95% CI: 0.72-1.02; p = 0.082). Receptor-binding domain-specific IgG levels and serum neutralisation capacity against different SARS-CoV-2 variants were higher after the third dose than after the second dose in the homologous regimen group, but not in the heterologous group.ConclusionThe advantage conferred by heterologous vaccination was lost after the third dose in terms of both protection and immunogenicity. Immunological measurements 1 month after vaccination suggest that heterologous vaccination induces maximal immunity after the second dose, whereas the third dose is required to reach the same level in individuals with a homologous regimen.

Biochemical Analysis of the Blood of Cattle after Vaccination with a Heterologous Vaccine for Lumpy Skin Disease.

We studied the biochemical parameters of the blood of cattle after immunization against lumpy skin disease with a vaccine made from an attenuated heterologous goat pox virus (strain G20-LKV). Blood samples were obtained from animals on days 7, 14, and 21 after vaccination. The vaccine did not affect biochemical parameters of the blood. A slight increase in total protein and AST on day 14 indicates the expected reactions to the stimulation of the immune system after vaccination. The levels of direct and total bilirubin, ALT, urea, glucose, cholesterol, and creatinine in vaccinated animals remained within the physiological limits.

A DNA Prime and MVA Boost Strategy Provides a Robust Immunity against Infectious Bronchitis Virus in Chickens.

Infectious bronchitis (IB) is an acute respiratory disease of chickens caused by the avian coronavirus Infectious Bronchitis Virus (IBV). Modified Live Virus (MLV) vaccines used commercially can revert to virulence in the field, recombine with circulating serotypes, and cause tissue damage in vaccinated birds. Previously, we showed that a mucosal adjuvant system, QuilA-loaded Chitosan (QAC) nanoparticles encapsulating plasmid vaccine encoding for IBV nucleocapsid (N), is protective against IBV. Herein, we report a heterologous vaccination strategy against IBV, where QAC-encapsulated plasmid immunization is followed by Modified Vaccinia Ankara (MVA) immunization, both expressing the same IBV-N antigen. This strategy led to the initiation of robust T-cell responses. Birds immunized with the heterologous vaccine strategy had reduced clinical severity and >two-fold reduction in viral burden in lachrymal fluid and tracheal swabs post-challenge compared to priming and boosting with the MVA-vectored vaccine alone. The outcomes of this study indicate that the heterologous vaccine platform is more immunogenic and protective than a homologous MVA prime/boost vaccination strategy.

The Serological Response in Cattle following Administration of a Heterologous Sheep Pox Virus Strain Vaccine for Protection from Lumpy Skin Disease; Current Situation in Armenia.

Lumpy skin disease (LSD) is a highly infectious viral disease of cattle caused by LSD virus (LSDV), which was first reported in Armenia in late 2015. It was identified in pasture-raised cattle near the border with Iran. Currently, vaccination plays a key role in preventing further incursion of disease in high-risk areas. The purpose of this work was to assess the quality of vaccination currently used in Armenia by determining the immune response of the heterologous dry culture sheep pox virus-based vaccine against LSD in cattle. Seroprevalence and seroconversion testing was carried out using an ELISA to detect specific antibodies against LSD before and 30 days after vaccination in three adjacent regions of Armenia (Ararat, Armavir, Gegharkunik). Ixodes ticks were also examined for the presence of LSDV via real-time PCR. We found that the heterologous vaccine used in Armenia creates a high level of population immunity of 86.09% (83.83-87.97%) and no adverse side effects were observed in cattle. Of the 6 types of Ixodes ticks identified and tested, we found no evidence of LSDV circulating in these vectors. These results suggest that regular serological monitoring via ELISA and heterologous vaccination should continue in areas of Armenia at high risk for incursion of LSD to reduce the spread of this highly infectious transboundary disease.

Protection of Grouper Against Cryptocaryon irritans by Immunization With Tetrahymena thermophila and Protective Cross-Reactive Antigen Identification.

Vaccination is an effective method to prevent Cryptocaryon irritans infection. Although some vaccines have been developed, large-scale production of these vaccines is costly. Development of a heterogenous vaccine generated by low-cost antigens is an alternative method. In the present study, grouper immunized with Tetrahymena thermophila, a free-living ciliate that easily grows in inexpensive culture media at high density, showed protective immunity against C. irritans infection. Higher immobilization against C. irritans theronts was detected in T. thermophila-immunized grouper serum, which suggested the existence of a cross-reactive antibody in the serum. By immunoprecipitation and mass spectrometry analyses, tubulin was identified as a potential cross-reactive antigen between C. irritans and T. thermophila. Recombinant T. thermophila tubulin protein (rTt-tubulin) and its antibody were prepared, and immunofluorescence showed that both C. irritans and T. thermophila cilia were stained by the anti-rTt-tubulin antibody. Grouper immunized with rTt-tubulin showed a reduced infective rate after the C. irritans challenge. An enhanced level of C. irritans-binding immunoglobulin M (IgM) antibody was detected in serum from rTt-tubulin-immunized grouper. Moreover, specific antibodies were also found in the mucus and tissue culture medium from rTt-tubulin-immunized grouper. Overall, these findings suggested that vaccination with T. thermophila elicits cross-reactive protective immunity in grouper against C. irritans, and T. thermophila may be a potential heterologous antigen for vaccine development.

Adopting an heterologous prime-boost strategy in COVID-19 vaccination: the need for locally generated evidence in Africa.

The reduction in the severity and prevalence of COVID-19 has been largely due to the rapid development and deployment of COVID-19 vaccines. Consequently, WHO, in partnership with the Coalition for Epidemic Preparedness Innovation, GAVI, the Vaccine Alliance, set up the COVID-19 Vaccines Global Access (COVAX) Initiative. The goal of this initiative is to prevent discrimination between high and low-income/middle-income countries and ensure equitable vaccine distribution. The first COVID-19 vaccine sent to most countries in the region through the COVAX initiative was the Oxford AstraZeneca (ChAdOx1 nCoV-19) vaccine. Due to the reduced protection against variants of concern, safety issues, and supply challenges of the AstraZeneca vaccine in some countries, heterologous booster dose with alternative vaccines for individuals who have received a prime dose of AstraZeneca. Moreover, vaccine mixing (heterologous vaccination) due to its superior immunogenicity and enhanced protection is being recommended even for individuals who are yet to be vaccinated. However, it is important that prior adoption, empirical data on immunogenicity, safety, and reactogenicity be locally generated in populations where such heterologous vaccine is to be implemented. Regrettably, such data from our search in all clinical trial databases is not ongoing in Africa as at the time of writing this manuscript. Therefore, this treatise advocates an experimental arm to generate such robust evidence. This will provide empirical evidence to guide this innovative approach aimed at ensuring equity and access to COVID-19 vaccines in LMICs, particularly countries within the African region.

Common Variable Immunodeficiency Associated with a De Novo IKZF1 Variant and a Low Humoral Immune Response to the SARS-CoV-2 Vaccine.

BACKGROUND AND AIMS: Common variable immunodeficiency (CVID) comprises a group of diseases with heterogeneous clinical and immunological manifestations. Several mutations have been identified in genes encoding proteins essential for immune function. Our aim was to phenotypically and genotypically characterize a patient diagnosed with CVID and study his response to the SARS-CoV-2 vaccine. METHODS: We performed a next-generation sequencing analysis, a CMIA, and an ELISA to analyze the humoral and cellular response to the SARS-CoV-2 vaccine, respectively. We also employed flow cytometry and immunoturbidimetry to assess the patient's global immune status. RESULTS: We found a low humoral but positive cellular response to the SARS-CoV-2 vaccine. NGS screening revealed a transition from guanine to adenine at position c.485 of the IKZF1 gene in heterozygosity, giving rise to the R162Q variant, which was not present in his parents. CONCLUSIONS: The R162Q variant of the IKZF1 gene has been associated with CVID type 13, but always with an autosomal dominant inheritance with high penetrance. Therefore, we present for the first time a case of CVID associated with a de novo heterozygous R162Q variant in the IKZF1 gene in a patient with a low humoral immune response to the complete COVID-19 vaccination program.

COVID-19 vaccine development based on recombinant viral and bacterial vector systems: combinatorial effect of adaptive and trained immunity.

Severe acute respiratory syndrome coronavirus 2 virus (SARS-CoV-2) infection, which causes coronavirus disease 2019 (COVID-19), has led to many cases and deaths worldwide. Therefore, a number of vaccine candidates have been developed to control the COVID-19 pandemic. Of these, to date, 21 vaccines have received emergency approval for human use in at least one country. However, the recent global emergence of SARS-CoV-2 variants has compromised the efficacy of the currently available vaccines. To protect against these variants, the use of vaccines that modulate T cell-mediated immune responses or innate immune cell memory function, termed trained immunity, is needed. The major advantage of a vaccine that uses bacteria or viral systems for the delivery of COVID-19 antigens is the ability to induce both T cell-mediated and humoral immune responses. In addition, such vaccine systems can also exert off-target effects via the vector itself, mediated partly through trained immunity; compared to other vaccine platforms, suggesting that this approach can provide better protection against even vaccine escape variants. This review presents the current status of the development of COVID-19 vaccines based on recombinant viral and bacterial delivery systems. We also discuss the current status of the use of licensed live vaccines for other infections, including BCG, oral polio and MMR vaccines, to prevent COVID-19 infections.

Tuberculosis, BCG Vaccination, and COVID-19: Are They Connected?

Evidence from multiple scientific studies suggests that the Bacillus Calmette-Guérin (BCG) vaccine, widely used worldwide as a preventive measure against tuberculosis, also offers crossprotection against other pathogens. This review aimed to gather data from research that studied the mechanisms involved in the immunological protection induced by the BCG vaccine, which may be important in the control of viral infections, such as COVID-19. Through a literature review, we compiled information about the different BCG strains used worldwide, as well as the responses and protection elicited by them. We commented on the mechanisms of immune response to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), and we discussed the possibility of cross-protection of different BCG strains on the control of COVID-19. Due to the immunomodulatory properties of BCG, some BCG strains were able to induce an effective cellular immune response and, through epigenetic modifications, activate cells of the innate immune system, such as monocytes, macrophages and natural killer cells, which are crucial for the control of viral infections. Although several vaccines have already been developed and used in an attempt to control the COVID-19 pandemic, some BCG vaccine strains may help stimulate the basal defences against these pathogens and can be used as additional defences in this and future pandemics.

Genetic Evidence of Multiple Introductions of Lumpy Skin Disease Virus into Saratov Region, Russia.

Lumpy skin disease virus (LSDV) is the causative agent of lumpy skin disease (LSD) that has been recently reported in the South-East and North Asian parts of the Russian Federation. During 2017-2019, there were more than 30 LSD outbreaks in Saratov Region despite active inoculation of cattle with heterologous vaccine. Importantly, the first case of the novel recombinant LSDV strain was reported here in 2017. This study aimed to determine the main clonal lineage(s) of LSDV strains circulated within Saratov Region and other regions of Russia since the first introduction of LSDV. The molecular typing and subtyping based on the coding regions of the G-protein-coupled chemokine receptor (GPCR) gene resulted in a discrimination of all outbreak-related LSDV strains into two main types, such as Type I and Type II, and subtypes Ia-d and IIa-g. Phylogenetically, eleven LSDV lineages were revealed in Russia including the five ones in Saratov Region. They were the following: (i) the Neethling wild Type Ia/2017; (ii) the recombinant Saratov IIc/2017/2019; (iii) the specific Dergachevskyi IId/2017; (iv) the Khvalynsky IIg/2018, and (v) the Haden-Type IIa lineage for the six LSDV strains detected in cattle immunized with heterologous vaccine during the last LSD outbreak in the Saratov Region, Nesterovo Village, in 2019 (Nesterovo-2019 strains). A single LSDV strain detected in Saratov Region in 2017 had the same Type Ia that was identified in 2016 in the bordered Republic of Kazakhstan. Phylogeographic analysis demonstrated three nominal clusters of LSDV types in the following Russian Federation territories: (I) the Central European part; (II) the South-East of the European part; (III) the North Asian part. Cluster I was represented by mainly Type I strains, while both Clusters 2 and 3 contained predominantly Type II strains. The Clusters I and II partially overlapped, while Cluster 3 was separate. Multiple introductions of LSDV into Saratov Region in 2017-2019 using GPCR-based molecular typing and subtyping were revealed. This scheme is a promising tool for molecular discrimination of LSDV strains derived from both vaccinated and unvaccinated against LSD cattle as well as for molecular epidemiology.

Localized and Systemic Immune Responses against SARS-CoV-2 Following Mucosal Immunization.

The rapid transmission of SARS-CoV-2 in the USA and worldwide necessitates the development of multiple vaccines to combat the COVID-19 global pandemic. Previously, we showed that a particulate adjuvant system, quil-A-loaded chitosan (QAC) nanoparticles, can elicit robust immunity combined with plasmid vaccines when used against avian coronavirus. Here, we report on the immune responses elicited by mucosal homologous plasmid and a heterologous immunization strategy using a plasmid vaccine and a Modified Vaccinia Ankara (MVA) expressing SARS-CoV-2 spike (S) and nucleocapsid (N) antigens. Only the heterologous intranasal immunization strategy elicited neutralizing antibodies against SARS-CoV-2 in serum and bronchoalveolar lavage of mice, suggesting a protective vaccine. The same prime/boost strategy led to the induction of type 1 and type 17 T-cell responses and polyfunctional T-cells expressing multiple type 1 cytokines (e.g., IFN-γ, TNFα, IL-2) in the lungs and spleens of vaccinated mice. In contrast, the plasmid homologous vaccine strategy led to the induction of local mono and polyfunctional T-cells secreting IFN-γ. Outcomes of this study support the potential of QAC-nano vaccines to elicit significant mucosal immune responses against respiratory coronaviruses.

Heterologous vaccine regimen: Stakeholder acceptance and implementation considerations.

Heterologous vaccine regimens deliver antigens through different vaccine components or vector types at sequential time points. Clinical development shows promising results and several candidates may be progressing to licensure in the coming years. This study aimed at exploring future acceptance and uptake of such regimens (also called heterologous prime-boost) and to identify implementation-associated benefits and challenges. Survey tools were developed based on findings from a previous literature search shared with the study team, and exploratory interviews with global stakeholders. An online survey and key informant interviews in six countries were conducted with stakeholders at national and sub-national level, including policy-makers, regulators and implementers. The interview guide and the online survey covered: (a) awareness of, and knowledge about, heterologous vaccine regimens; (b) rating of regimen-associated perceived benefits and challenges; (c) anticipation of possible challenges in relation to four hypothetical introduction scenarios; (d) potential acceptance benefits and challenges at the policy, health facility and recipient level. Sixty-two interviews were conducted at national level. The online survey was completed by 50 participants. Across the four introduction scenarios, respondents considered the highest potential for the introduction of heterologous regimens for immunoprophylaxis was among adolescents/adults for diseases against which no vaccines are currently available. Most reservations were related to logistics, record keeping, and recipient compliance. Adding a new heterologous vaccine regimen to the routine immunization calendar for children was considered feasible if it could generate an increased and longer-term immune response. Introduction in preparation of or following a disease outbreak was considered less favourably, with respondents stressing the difficulty of logistics in emergency situations, and the potential lag in the onset of protection. The recent approval of the first heterologous vaccine regimen for the prevention of Ebola Virus Disease will soon bring new light to the topic.