Live Attenuated Virus Vaccine Research Articles

Live-attenuated virus vaccine defective in RNAi suppression induces rapid protection in neonatal and adult mice lacking mature B and T cells

Global control of infectious diseases depends on the continuous development and deployment of diverse vaccination strategies. Currently available live-attenuated and killed virus vaccines typically take a week or longer to activate specific protection by the adaptive immunity. The mosquito-transmitted Nodamura virus (NoV) is attenuated in mice by mutations that prevent expression of the B2 viral suppressor of RNA interference (VSR) and consequently, drastically enhance in vivo production of the virus-targeting small-interfering RNAs. We reported recently that 2 d after immunization with live-attenuated VSR-disabled NoV (NoVΔB2), neonatal mice become fully protected against lethal NoV challenge and develop no detectable infection. Using Rag1-/- mice that produce no mature B and T lymphocytes as a model, here we examined the hypothesis that adaptive immunity is dispensable for the RNAi-based protective immunity activated by NoVΔB2 immunization. We show that immunization of both neonatal and adult Rag1-/- mice with live but not killed NoVΔB2 induces full protection against NoV challenge at 2 or 14 d postimmunization. Moreover, NoVΔB2-induced protective antiviral immunity is virus-specific and remains effective in adult Rag1-/- mice 42 and 90 d after a single-shot immunization. We conclude that immunization with the live-attenuated VSR-disabled RNA virus vaccine activates rapid and long-lasting protective immunity against lethal challenges by a distinct mechanism independent of the adaptive immunity mediated by B and T cells. Future studies are warranted to determine whether additional animal and human viruses attenuated by VSR inactivation induce similar protective immunity in healthy and adaptive immunity-compromised individuals.

Potential Pathogenicity and Genetic Characteristics of a Live-Attenuated Classical Swine Fever Virus Vaccine Derivative Variant

Classical swine fever (CSF), caused by CSF virus (CSFV), is a highly contagious disease affecting pigs and causing massive pig production losses with severe global economic recession. The immunization of live-attenuated vaccines is still one of the key measures to CSFV management in endemic countries. However, there are also strong controversies about the usage of live-attenuated vaccines, particularly in pregnant sows and young pigs, such as in Europe, where domestic pigs are routinely not vaccinated until severe outbreaks occur. Here, we report a CSF outbreak in a pig farm in China, which affected more than 90% of the delivery sows and led to ∼45% birth loss. Surprisingly, phylogenetic analysis showed that the CSFV isolate (named CSFV/HeNLY2022, GenBank No. OR195698) was clustered into subgenotype 1.1a, closely together with the live-attenuated vaccine strains. Further genomic analysis also revealed that the isolate CSFV/HeNLY2022 shared the highest nucleotide identity of 99.7% with the C/HVRI vaccine strain (C-strain, GenBank No. AY805221). Moreover, compared to the C/HVRI strain, a total of eight amino acid mutations, distributed in Erns (H436thY and S476thR), E1 (T502thI and P581thT), E2 (M979thK and A1061thS), NS5A (A2980thT), and NS5B (I3818thM), were characterized in the CSFV/HeNLY2022 isolate. Our results suggested that the CSF outbreak was most likely caused by the live-attenuated CSFV vaccine or its derivative. It raises concern that the unscientific application of CSFV vaccines could potentially lead to CSFV spread in pigs. It is needed to perform a more rigorous evaluation of the safety of the C-strain-derived vaccines in combination with other different live-attenuated vaccines.

Mutations in the F protein of the live-attenuated respiratory syncytial virus vaccine candidate ΔNS2/Δ1313/I1314L increase the stability of infectivity and content of prefusion F protein.

Respiratory syncytial virus (RSV) is the leading viral cause of bronchiolitis and pneumonia in infants and toddlers, but there currently is no licensed pediatric vaccine. A leading vaccine candidate that has been evaluated for intranasal immunization in a recently completed phase 1/2 clinical trial is an attenuated version of RSV strain A2 called RSV/ΔNS2/Δ1313/I1314L (hereafter called ΔNS2). ΔNS2 is attenuated by deletion of the interferon antagonist NS2 gene and introduction into the L polymerase protein gene of a codon deletion (Δ1313) that confers temperature-sensitivity and is stabilized by a missense mutation (I1314L). Previously, introduction of four amino acid changes derived from a second RSV strain "line 19" (I79M, K191R, T357K, N371Y) into the F protein of strain A2 increased the stability of infectivity and the proportion of F protein in the highly immunogenic pre-fusion (pre-F) conformation. In the present study, these four "line 19" assignments were introduced into the ΔNS2 candidate, creating ΔNS2-L19F-4M. During in vitro growth in Vero cells, ΔNS2-L19F-4M had growth kinetics and peak titer similar to the ΔNS2 parent. ΔNS2-L19F-4M exhibited an enhanced proportion of pre-F protein, with a ratio of pre-F/total F that was 4.5- to 5.0-fold higher than that of the ΔNS2 parent. The stability of infectivity during incubation at 4°C, 25°C, 32°C and 37°C was greater for ΔNS2-L19F-4M; for example, after 28 days at 32°C, its titer was 100-fold greater than ΔNS2. ΔNS2-L19F-4M exhibited similar levels of replication in human airway epithelial (HAE) cells as ΔNS2. The four "line 19" F mutations were genetically stable during 10 rounds of serial passage in Vero cells. In African green monkeys, ΔNS2-L19F-4M and ΔNS2 had similar growth kinetics, peak titer, and immunogenicity. These results suggest that ΔNS2-L19F-4M is an improved live attenuated vaccine candidate whose enhanced stability may simplify its manufacture, storage and distribution, which merits further evaluation in a clinical trial in humans.

Restoration of virulence in the attenuated Candid#1 vaccine virus requires reversion at both positions 168 and 427 in the envelope glycoprotein GPC.

Live-attenuated virus vaccines provide long-lived protection against viral disease but carry inherent risks of residual pathogenicity and genetic reversion. The live-attenuated Candid#1 vaccine was developed to protect Argentines against lethal infection by the Argentine hemorrhagic fever arenavirus, Junín virus. Despite its safety and efficacy in Phase III clinical study, the vaccine is not licensed in the US, in part due to concerns regarding the genetic stability of attenuation. Previous studies had identified a single F427I mutation in the transmembrane domain of the Candid#1 envelope glycoprotein GPC as the key determinant of attenuation, as well as the propensity of this mutation to revert upon passage in cell culture and neonatal mice. To ascertain the consequences of this reversion event, we introduced the I427F mutation into recombinant Candid#1 (I427F rCan) and investigated the effects in two validated small-animal models: in mice expressing the essential virus receptor (human transferrin receptor 1; huTfR1) and in the conventional guinea pig model. We report that I427F rCan displays only modest virulence in huTfR1 mice and appears attenuated in guinea pigs. Reversion at another attenuating locus in Candid#1 GPC (T168A) was also examined, and a similar pattern was observed. By contrast, virus bearing both revertant mutations (A168T+I427F rCan) approached the lethal virulence of the pathogenic Romero strain in huTfR1 mice. Virulence was less extreme in guinea pigs. Our findings suggest that genetic stabilization at both positions is required to minimize the likelihood of reversion to virulence in a second-generation Candid#1 vaccine.IMPORTANCELive-attenuated virus vaccines, such as measles/mumps/rubella and oral poliovirus, provide robust protection against disease but carry with them the risk of genetic reversion to the virulent form. Here, we analyze the genetics of reversion in the live-attenuated Candid#1 vaccine that is used to protect against Argentine hemorrhagic fever, an often-lethal disease caused by the Junín arenavirus. In two validated small-animal models, we find that restoration of virulence in recombinant Candid#1 viruses requires back-mutation at two positions specific to the Candid#1 envelope glycoprotein GPC, at positions 168 and 427. Viruses bearing only a single change showed only modest virulence. We discuss strategies to genetically harden Candid#1 GPC against these two reversion events in order to develop a safer second-generation Candid#1 vaccine virus.

Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses.

Single-dose, immunogenic DNA (iDNA) vaccines coding for whole live-attenuated viruses are reviewed. This platform, sometimes called immunization DNA, has been used for vaccine development for flavi- and alphaviruses. An iDNA vaccine uses plasmid DNA to launch live-attenuated virus vaccines in vitro or in vivo. When iDNA is injected into mammalian cells in vitro or in vivo, the RNA genome of an attenuated virus is transcribed, which starts replication of a defined, live-attenuated vaccine virus in cell culture or the cells of a vaccine recipient. In the latter case, an immune response to the live virus vaccine is elicited, which protects against the pathogenic virus. Unlike other nucleic acid vaccines, such as mRNA and standard DNA vaccines, iDNA vaccines elicit protection with a single dose, thus providing major improvement to epidemic preparedness. Still, iDNA vaccines retain the advantages of other nucleic acid vaccines. In summary, the iDNA platform combines the advantages of reverse genetics and DNA immunization with the high immunogenicity of live-attenuated vaccines, resulting in enhanced safety and immunogenicity. This vaccine platform has expanded the field of genetic DNA and RNA vaccines with a novel type of immunogenic DNA vaccines that encode entire live-attenuated viruses.

Lack of a non-specific protective effect of prior yellow fever vaccination against COVID-19.

Live-attenuated virus vaccines, such as yellow fever vaccine, exhibit non-specific immunomodulatory effects, prompting exploration of their potential impact on COVID-19 pandemic. In this retrospective study, we didn’t observe an association between prior yellow fever vaccination with SARS-CoV-2 infection incidence. In the multivariate model, no association was found with COVID-19 prognosis.

Live-attenuated vaccination for measles, mumps, and rubella in pediatric liver transplantation.

Infections are a serious short- and long-term problem after pediatric organ transplantation. In immunocompromised patients, they can lead to transplant rejection or a severe course with a sometimes fatal outcome. Vaccination is an appropriate means of reducing morbidity and mortality caused by vaccine-preventable diseases. Unfortunately, due to the disease or its course, it is not always possible to establish adequate vaccine protection against live-attenuated viral vaccines (LAVVs) prior to transplantation. LAVVs such as measles, mumps, and rubella (MMR) are still contraindicated in solid organ transplant recipients receiving immunosuppressive therapy (IST), thus creating a dilemma. This review discusses whether, when, and how live-attenuated MMR vaccines can be administered effectively and safely to pediatric liver transplant recipients based on the available data. We searched PubMed for literature on live-attenuated MMR vaccination in pediatric liver transplantation (LT). Nine prospective observational studies and three retrospective case series were identified in which at least 833 doses of measles vaccine were administered to 716 liver transplant children receiving IST. In these selected patients, MMR vaccination was well tolerated and no serious adverse reactions to the vaccine were observed. In addition, an immune response to the vaccine was demonstrated in patients receiving IST. Due to inadequate vaccine protection in this high-risk group, maximum efforts must be made to ensure full immunization. MMR vaccination could also be considered for unprotected patients after LT receiving IST following an individual risk assessment, as severe harm from live vaccines after liver transplantation has been reported only very rarely. To this end, it is important to establish standardized and simple criteria for the selection of suitable patients and the administration of the MMR vaccine to ensure safe use.

Identification and quantitation of multiple variants in RNA virus genomes.

The goal of the study was to identify and characterize RNA virus variants containing mutations spread over genomic distances >5 kb. As proof of concept, high-quality viral RNA of the Dengue 2 component of Takeda's tetravalent dengue vaccine candidate (TDV-2) was used to develop a reverse transcription-polymerase chain reaction protocol to amplify a ∼5.3 kb cDNA segment that contains the three genetic determinants of TDV-2 attenuation. Unique molecular identifiers were incorporated into each viral cDNA molecule for PacBio library preparation to improve the quantitative precision of the observed variants at the attenuation loci. Following assay optimization, PacBio long-read sequencing was validated with multiple clone-derived TDV-2 revertant variants and four complex revertant mixtures containing various compositions of TDV-2 and revertant viruses. PacBio sequencing analysis correctly identified and quantified variant composition in all tested samples, demonstrating that TDV-2 revertants could be identified and characterized and supporting the use of this method in the differentiation and quantification of complex variants of other RNA viruses. Long-read sequencing can identify complex RNA virus variants containing multiple mutations on a single-genome molecule, which is useful for in-depth genetic stability and revertant detection of live-attenuated viral vaccines, as well as research in virus evolution to reveal mechanisms of immune evasion and host cell adaption.

Detection of interferon alpha and beta receptor subunit 1 (IFNAR1) loss-of-function Glu386∗ variant by tri-allelic genotyping

Mutations of the human interferon alpha and beta receptor subunit 1 (IFNAR1) gene are associated with severe viral infections. Individuals homozygous for the Glu386∗ variant have impaired type I interferon signalling and can suffer severe illness when exposed to certain viruses and live attenuated virus vaccines. Glu386∗ heterozygotes are clinically unaffected, but can pass the variant allele to their descendants. We aimed to develop an assay that can identify IFNAR1 Glu386∗ homozygotes and heterozygotes to support urgent clinical diagnosis, and that can use dried blood spots (DBS) sent at ambient temperature to overcome geographical logistical challenges in the South Pacific region. The tri-allelic genotyping assay interrogates a single nucleotide polymorphism (rs201609461) located in IFNAR1. The reference allele G encodes for wild-type IFNAR1. Minor alleles A (c.1156G>A) and T (c.1156G>T) encode for Glu386Lys and a truncated IFNAR1 protein (p.Glu386∗), respectively. Synthetic oligonucleotides were mixed in equal molar ratio to create six different genotypes which were randomly assigned to 960 genotyping reactions by R software. Three different fluorescence probes were designed to discriminate the three alleles (G, T and A) within a pair of flanking primers in a single genotyping reaction. The assay discriminated all three alleles using DBS from Guthrie cards randomly spiked with synthetic oligonucleotides. We correctly identified all the different genotypes in 960 reactions in these blinded experiments. These findings validate the genotyping assay for rapidly identifying the IFNAR1 Glu386∗ variant from DBS.

Zika Virus 101: A Mini Review

Zika virus is a mosquito-borne Flavivirus that is the focus of an ongoing pandemic and public health emergency. The Zika virus outbreak in Brazil in 2015, previously limited to sporadic cases in Africa and Asia, heralded a rapid spread across the Americas. Although most Zika virus infections are characterized by subclinical or mild flu-like illness, severe manifestations have been reported, including Guillain-Barre syndrome in adults and microcephaly in children born to infected mothers. There is no effective treatment or vaccine for the Zika virus; therefore, the public health response is primarily focused on preventing infections, especially in pregnant women. Despite the growing knowledge of this virus, questions remain regarding the vectors and reservoirs of the virus, pathogenesis, genetic diversity, and potential synergistic effects of coinfection with other circulating viruses. These questions highlight the need for research to optimize surveillance, patient management, and public health interventions in the current Zika virus epidemic .Zika virus (ZIKV) is an emerging arthropod-borne Flavivirus that leads to teratogenic effects and neurological disorders after infection. ZIKV infections are a serious global public health problem, leading scientists to increase research into antiviral and vaccines against the virus. These efforts are still ongoing, as the pathogenesis and immune evasion mechanisms of ZIKV are not yet fully understood. There are currently no specific vaccines or drugs approved for ZIKV; however, some are undergoing clinical trials. Notably, several strategies have been used to develop antiviral, including drugs that target viral and host proteins. In addition, drug reuse is preferred because it is cheaper and less timeconsuming than other strategies because the drugs used have already been approved for human use. Similarly, various platforms for vaccine design have been evaluated, including DNA, mRNA, peptide, protein, viral vectors, virus-like particles (VLPS), inactivated viruses, and live attenuated virus vaccines. These vaccines have been shown to induce specific humoral and cellular immune responses and reduce viremia and viral RNA in vitro and in vivo. Importantly, most of these vaccines have entered clinical trials. Understanding the mechanism of viral disease will provide better strategies for the development of therapeutic agents against ZIKV. This review provides a comprehensive summary of the viral pathogenesis of ZIKV and current progress in the development of vaccines and drugs against this virus.

Investigation of the safety of live attenuated varicella-zoster virus vaccination in patients with relapse-remitting multiple sclerosis treated with natalizumab: A case series and review of the literature.

It is generally recommended to avoid live attenuated vaccines in patients treated with high efficacy disease-modifying treatment (DMT). However, a delay in starting DMT in highly active or aggressive multiple sclerosis (MS) might lead to a significant disability. We aimed to report a case series of 16 highly active RRMS patients who received the live-attenuated varicella-zoster virus (VZV) vaccine during treatment with natalizumab. This retrospective case series was conducted between September 2015 and February 2022 at the MS Research Center of Sina and Qaem hospital, Tehran, Mashhad, Iran, to identify the outcome of highly active MS patients who received the live-attenuated VZV vaccine on natalizumab. Two males and 14 females were included in this study, with a mean age of 25.5±8.4-year-old. 10 patients were naïve cases of highly active MS, and six were escalated to natalizumab. The patients received two doses of live attenuated VZV vaccine after a mean of 6.72 cycles of natalizumab treatment. Except for the one who experienced mild chickenpox infection, no serious adverse event or disease activity was evident after vaccination. While our data do not confirm the safety of the live attenuated VZV vaccine in natalizumab recipients, it highlights the importance of case-by-case decision-making in MS management based on the risk-benefit assessment.

Efficacy of Rubella Vaccination after Co-Inoculation with Rhogam.

Congenital rubella syndrome is a constellation of birth defects that can have devastating consequences, impacting approximately 100,000 births worldwide each year. The incidence is much lower in countries that routinely vaccinate their population. In the US, postnatal immunization of susceptible women is an important epidemiological strategy for the prevention of rubella as the Center for Disease Control (CDC) does not recommend administering this vaccine during pregnancy due to its nature as a live attenuated virus vaccine. However, concerns that the co-administration of rubella vaccine with other immunoglobins (i.e., Rhogam) could compromise vaccine efficacy has produced warnings that can delay the administration of rubella vaccination postpartum, leaving women susceptible to the disease in subsequent pregnancies. We aimed to address whether the co-administration of the measles, mumps, and rubella (MMR) vaccine and Rhogam decreased antibody responses compared to those receiving only MMR vaccination. This retrospective cohort study utilized clinical data from 78 subjects who received the MMR vaccine and Rhogam after delivery and 45 subjects who received the MMR vaccine alone. Maternal demographics, pregnancy complications and rubella status at the start of a subsequent pregnancy were recorded for analysis. Overall, the two cohorts had similar baseline characteristics; however, lower parity was noted in the participants that received both MMR vaccination and Rhogam. Making assessments based on maternal antibody IgG index for rubella during the next pregnancy, we observed that 88% of the Rhogam + MMR vaccine group had positive serology scores, which was not significantly different from the 80% rate in the MMR-vaccine-only cohort (p = 0.2). In conclusion, no differences were observed in rubella immunity status in subsequent pregnancies in those mothers given both the MMR vaccine and Rhogam concurrently. Given these findings, warnings against co-administration of vaccines in combination with Rhogam appear unwarranted.

The Protective Efficacy of Single-Dose Nasal Immunization with Cold-Adapted Live-Attenuated MERS-CoV Vaccine against Lethal MERS-CoV Infections in Mice.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes severe diseases in humans. Camels act as intermediate hosts for MERS-CoV. Currently, no licensed vaccine is available for this virus. We have developed a potential candidate vaccine for MERS-CoV using the cold adaptation method. We cultivated the vaccine in Vero cells at temperatures as low as 22 °C. This live-attenuated vaccine virus showed high attenuation levels in transgenic mice with the MERS-CoV human receptor, dipeptidyl peptidase 4 (DPP4) (K18-hDPP4). The inoculated K18-hDPP4 mice exhibited no clinical signs such as death or body weight loss. Furthermore, no traces of infectious virus were observed when the tissues (nasal turbinate, brain, lung, and kidney) of the K18-hDPP4 mice infected with the cold-adapted vaccine strain were tested. A single intranasal dose of the vaccine administered to the noses of the K18-hDPP4 mice provided complete protection. We did not observe any deaths, body weight loss, or viral detection in the tissues (nasal turbinate, brain, lung, and kidney). Based on these promising results, the developed cold-adapted, attenuated MERS-CoV vaccine strain could be one of the candidates for human and animal vaccines.

Longitudinal humoral immune response and maternal immunity in horses after a single live-attenuated vaccination against African horse sickness during the disease outbreak in Thailand.

African horse sickness (AHS) has become a newly emerging disease after an outbreak in northeastern Thailand in March 2020. Mass vaccination in horses with live-attenuated AHS virus (AHSV) vaccine is essential for AHS control and prevention. This study aimed to monitor the longitudinal humoral immune response before and after a single vaccination using a live-attenuated vaccine against AHS in stallions, mares, and pregnant mares, including maternal immunity in foals born from pregnant mares during the outbreak in Thailand. A total of 13 stallions and 23 non-pregnant and 21 pregnant mares were vaccinated with live-attenuated AHSV vaccines. Serum samples from selected horses were collected on the day of vaccination and 1, 6, 8, 9, 10, and 12-months post-vaccination. Furthermore, seven serum samples of foals born from vaccinated pregnant mares were collected on parturition date and 1, 3, and 6-months old. The antibody titer against AHS in all collected serum samples was evaluated using a commercial enzyme-linked immunosorbent assay kit. All data were analyzed for mean and standard deviation for each group of samples using a spreadsheet program. Antibody titers between times were analyzed using a one-way analysis of variance as repeated measurement, and antibody titers between horse groups were analyzed using a general linear model for statistically significant differences when p < 0.05. In stallion and non-pregnant mare groups, there were no statistically significant differences in antibody titers in all 6 time periods after vaccination. The antibody titer in the pregnant mare group showed a non-statistically significant difference between each gestation stage, except at 8 months post-vaccination. Furthermore, increasing antibody titers on days 1 and 3 after receiving colostrum in foals indicate the major role of transcolostral antibody transfer for AHS. This study demonstrated that a single AHS vaccination using a live-attenuated vaccine could stimulate high antibody titers sufficient for AHS control and prevention during the outbreak in Thailand. Similarly, the antibody response of vaccinated horses of both genders, including various stages of pregnant mares, was statistically not different.

Compliance with yellow fever and measles vaccines in the revaccination program post-hematopoietic cell transplantation.

Measles, mumps, rubella, and even poliomyelitis outbreaks have recently perplexed infectious disease clinicians and epidemiologists globally due to the decline in vaccination coverage rates in children and adults. Measles and yellow fever (YF) have represented an increasing burden on the Brazilian public health system in recent decades. Both diseases are preventable by live-attenuated viral vaccines (LAVV), which have restricted use in hematopoietic cell transplant (HCT) recipients. Autologous and allogeneic HCT recipients returning for regular appointments at the outpatient clinic were invited to participate in the study. Patients transplanted for at least 2 years and with a printed copy of the vaccination record were included. We assessed the vaccination records of 273 HCT recipients after the second year of HCT (193 allogeneic and 80 autologous) and observed lower compliance with the YF vaccine (58 patients, 21.2%) than with the measles vaccine (138 patients, 50.5%, p ≤ .0001). This is the largest published series of YF vaccination in HCT recipients so far. No severe adverse events occurred. Although expected, chronic graft-versus-host disease (GVHD) did not affect the compliance with measles (p = .08) or YF vaccination (p = .7). Indeed, more allogeneic recipients received measles vaccine in comparison with autologous patients (p<.0001), suggesting that chronic GVHD was not the main reason for not being vaccinated. Children and allogeneic HCT were more likely to receive measles vaccine. Time elapsed from HCT >5 years favored both measles and YF vaccination. A better understanding of the reasons for low compliance with LAVV is necessary to overcome this problem.

Advances in Alpha Herpes Viruses Vaccines for Human.

Alpha herpes simplex viruses are an important public health problem affecting all age groups. It can produce from common cold sores and chicken pox to severe conditions like encephalitis or newborn mortality. Although all three subtypes of alpha herpes viruses have a similar structure, the produced pathology differs, and at the same time, the available prevention measures, such as vaccination. While there is an available and efficient vaccine for the varicella-zoster virus, for herpes simplex virus 1 and 2, after multiple approaches from trivalent subunit vaccine to next-generation live-attenuated virus vaccines and bioinformatic studies, there is still no vaccine available. Although there are multiple failed approaches in present studies, there are also a few promising attempts; for example, the trivalent vaccine containing herpes simplex virus type 2 (HSV-2) glycoproteins C, D, and E (gC2, gD2, gE2) produced in baculovirus was able to protect guinea pigs against vaginal infection and proved to cross-protect against HSV-1. Another promising vaccine is the multivalent DNA vaccine, SL-V20, tested in a mouse model, which lowered the clinical signs of infection and produced efficient viral eradication against vaginal HSV-2. Promising approaches have emerged after the COVID-19 pandemic, and a possible nucleoside-modified mRNA vaccine could be the next step. All the approaches until now have not led to a successful vaccine that could be easy to administer and, at the same time, offer antibodies for a long period.

One year antibody persistence and safety of a live-attenuated chikungunya virus vaccine candidate (VLA1553) in adults aged 18 years and above

VLA1553 is a live-attenuated chikungunya virus (CHIKV) vaccine candidate designed for active immunization as a prophylactic measure for individuals travelling to or living in endemic areas. Due to the sporadic epidemic occurrence of chikungunya, an immunological surrogate to assess clinical efficacy was accepted by regulators (FDA and EMA). To evaluate persistence of antibodies annually from 1 to at least 5 years after a single immunization with VLA1553. This phase 3 open-label, single arm long term antibody persistence and safety trial (VLA1553-303) follows a subset (N=363) of VLA1553 vaccinees from the pivotal phase 3 trial (VLA1553-301) where 4,115 adult participants received VLA1553 or placebo. The main aim of VLA1553-303 is to annually assess (at least until Year 5) the proportion of participants from study VLA1553-301 with seroresponse (defined as μPRNT ≥150). Additionally, the frequency and relatedness of any serious adverse event (SAE) until Year 2 is monitored. This presentation outlines the immunogenicity and safety data collected until Year 1. VLA1553-303 met its primary endpoint with a participant seroresponse rate of 98.9% at Year 1. Regarding GMTs, the initial Day 29 GMT for the group followed in the long term study was 3489 and remained high, with 1009 at Day 180 and 1056 at Year 1. Moreover, in older adults aged ≥65 years, antibody persistence was similar to younger adults throughout the follow-up. Four SAEs were reported in participants in study VLA1553-303 from 6 to 12 months post-vaccination. All cases were assessed as not related by the investigators, furthermore there was no persistent adverse event of special interest thus confirming that no safety concern was identified in study VLA1553-303 until Year 1. VLA1553-303 demonstrated that antibody persistence was confirmed at Year 1 post-vaccination as a high seroresponse was maintained throughout the study. Furthermore, no safety concern was identified with all four SAEs being assessed as not related by the investigators; the safety profile from earlier studies was confirmed. This study further reinforces the VLA1553-301 results showing VLA1553 as a possible effective prevention of CHIKV disease. R. M. Valneva Austria GmbH, Vienna, Austria S. T. Valneva Austria GmbH, Vienna, Austria M. S. Valneva Austria GmbH, Vienna, Austria S. H. Valneva Austria GmbH, Vienna, Austria R. H. Valneva Austria GmbH, Vienna, Austria K. K. Valneva Austria GmbH, Vienna, Austria R. M. Valneva Austria GmbH, Vienna, Austria O. Z. Valneva Austria GmbH, Vienna, Austria N. W. Valneva Austria GmbH, Vienna, Austria K. D. Valneva Austria GmbH, Vienna, Austria V. B. Valneva Austria GmbH, Vienna, Austria S. E. Valneva Austria GmbH, Vienna, Austria J.C. J Valneva Austria GmbH, Vienna, Austria

Immune response following safer administration of recombinant Salmonella Typhimurium harboring ASFV antigens in pigs

African swine fever virus (ASFV) is a contagious epizootic pathogen adversely affecting porcine industry in Asian and European countries. Till date, 8 serotypes and 24 genotypes of the virus have been reported. Few live attenuated virus vaccine studies have reported to provide complete protection against ASFV infection but biohazard concern still remain. Recombinant subunit antigens are capable of providing cellular and humoral immunity in porcine, but not a single vaccine has hit the market yet. In the present study, we attempted to use recombinant Salmonella Typhimurium JOL912 strain harboring ASFV antigens (rSal-ASFV) to investigate its immunostimulant effect in porcine. Post intramuscular administration, we observed significant increment in the levels of helper T cells, cytotoxic T cells, natural killer (NK) cells, and immunoglobulin (i.e. IgG, IgA, and IgM) levels in rSal-ASFV treated groups. Further RT-PCR analysis indicated the increased expression of MHC-I, MHC-II, CD80/86, NK cell receptors (NKp30, NKp44, and NKp46) and cytokines while ELIspot analysis revealed significant production of IFN-γ in rSal-ASFV treated groups. Taken together, we are able to demonstrate that rSal-ASFV could elicit a non-specific cellular as well as humoral immune response. However, additional antigen specific immunity data is needed to evaluate its efficacy. Intramuscular administration of rSal-ASFV was found to be safe and immunostimulant in nature without any side-effects and may serve as an excellent option for in-vivo antigen delivery in pigs.

Development of SARS-CoV-2 Vaccine: Challenges and Prospects.

The WHO declared coronavirus disease 2019 (COVID-19) a pandemic in March 2020, which was caused by novel coronavirus severe acute respiratory coronavirus 2 (SARS-CoV-2). SARS-CoV-2 made its first entry into the world in November 2019, and the first case was detected in Wuhan, China. Mutations in the SARS-CoV-2 genome distressed life in almost every discipline by the extended production of novel viral variants. In this article, authorized SARS-CoV-2 vaccines including mRNA vaccines, DNA vaccines, subunit vaccines, inactivated virus vaccines, viral vector vaccine, live attenuated virus vaccines and mix and match vaccines will be discussed based on their mechanism, administration, storage, stability, safety and efficacy. The information was collected from various journals via electronic searches including PubMed, Science Direct, Google Scholar and the WHO platform. This review article includes a brief summary on the pathophysiology, epidemiology, mutant variants and management strategies related to COVID-19. Due to the continuous production and unsatisfactory understanding of novel variants of SARS-CoV-2, it is important to design an effective vaccine along with long-lasting protection against variant strains by eliminating the gaps through practical and theoretical knowledge. Consequently, it is mandatory to update the literature through previous and ongoing trials of vaccines tested among various ethnicities and age groups to gain a better insight into management strategies and combat complications associated with upcoming novel variants of SARS-CoV-2.

Interference between enteric viruses and live-attenuated rotavirus vaccine virus in a healthy Australian birth cohort.

Rotavirus vaccines have reduced effectiveness in high mortality settings. Interference between enteric viruses and live-attenuated oral vaccine strains may be a factor. In a birth cohort of healthy Australian infants, parents collected weekly stool samples. Three-hundred and eighty-one paired swabs collected within 10-days of RotaTeq (Merck, Pennsylvania, USA.) vaccination from 140 infants were tested for 10 enteric viruses and RotaTeq strains. Collectively, both RNA and DNA viruses were negatively associated with RotaTeq shedding (adjusted odds ratio 0.29 [95% confidence interval [0.14─0.58]) and 0.30 [0.11─0.78], respectively). Enteric viruses may interfere with RotaTeq replication in the gut and thus RotaTeq stool shedding.