Live Attenuated Virus Vaccine Research Articles

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.

Live-attenuated vaccine sCPD9 elicits superior mucosal and systemic immunity to SARS-CoV-2 variants in hamsters

Vaccines play a critical role in combating the COVID-19 pandemic. Future control of the pandemic requires improved vaccines with high efficacy against newly emerging SARS-CoV-2 variants and the ability to reduce virus transmission. Here we compare immune responses and preclinical efficacy of the mRNA vaccine BNT162b2, the adenovirus-vectored spike vaccine Ad2-spike and the live-attenuated virus vaccine candidate sCPD9 in Syrian hamsters, using both homogeneous and heterologous vaccination regimens. Comparative vaccine efficacy was assessed by employing readouts from virus titrations to single-cell RNA sequencing. Our results show that sCPD9 vaccination elicited the most robust immunity, including rapid viral clearance, reduced tissue damage, fast differentiation of pre-plasmablasts, strong systemic and mucosal humoral responses, and rapid recall of memory T cells from lung tissue after challenge with heterologous SARS-CoV-2. Overall, our results demonstrate that live-attenuated vaccines offer advantages over currently available COVID-19 vaccines.

Cross-Protection of an Inactivated and a Live-Attenuated Lumpy Skin Disease Virus Vaccine against Sheeppox Virus Infections in Sheep.

Sheeppox virus (SPPV) (genus Capripoxvirus, family Poxviridae) infections are a highly virulent and contagious disease of sheep with a high morbidity and mortality, especially in naïve populations and young animals. For the control of SPPV, homologous and heterologous live-attenuated vaccines are commercially available. In our study, we compared a commercially available live-attenuated lumpy skin disease virus (LSDV) vaccine strain (Lumpyvax) with our recently developed inactivated LSDV vaccine candidate regarding their protective efficacy against SPPV in sheep. Both vaccines were proven to be safe in sheep, and neither clinical signs nor viremia could be detected after vaccination and challenge infection. However, the local replication of the challenge virus in the nasal mucosa of previously vaccinated animals was observed. Because of the advantages of an inactivated vaccine and its heterologous protection efficacy against SPPV in sheep, our inactivated LSDV vaccine candidate is a promising additional tool for the prevention and control of SPPV outbreaks in the future.

Vaccine Candidates against Arenavirus Infections.

The viral family Arenaviridae contains several members that cause severe, and often lethal, diseases in humans. Several highly pathogenic arenaviruses are classified as Risk Group 4 agents and must be handled in the highest biological containment facility, biosafety level-4 (BSL-4). Vaccines and treatments are very limited for these pathogens. The development of vaccines is crucial for the establishment of countermeasures against highly pathogenic arenavirus infections. While several vaccine candidates have been investigated, there are currently no approved vaccines for arenavirus infection except for Candid#1, a live-attenuated Junin virus vaccine only licensed in Argentina. Current platforms under investigation for use include live-attenuated vaccines, recombinant virus-based vaccines, and recombinant proteins. We summarize here the recent updates of vaccine candidates against arenavirus infections.

Characterization of Live-Attenuated Powassan Virus Vaccine Candidates Identifies an Efficacious Prime-Boost Strategy for Mitigating Powassan Virus Disease in a Murine Model

Powassan virus (POWV) is an emerging tick-borne virus and cause of lethal encephalitis in humans. The lack of treatment or prevention strategies for POWV disease underscores the need for an effective POWV vaccine. Here, we took two independent approaches to develop vaccine candidates. First, we recoded the POWV genome to increase the dinucleotide frequencies of CpG and UpA to potentially attenuate the virus by raising its susceptibility to host innate immune factors, such as the zinc-finger antiviral protein (ZAP). Secondly, we took advantage of the live-attenuated yellow fever virus vaccine 17D strain (YFV-17D) as a vector to express the structural genes pre-membrane (prM) and envelope (E) of POWV. The chimeric YFV-17D-POWV vaccine candidate was further attenuated for in vivo application by removing an N-linked glycosylation site within the nonstructural protein (NS)1 of YFV-17D. This live-attenuated chimeric vaccine candidate significantly protected mice from POWV disease, conferring a 70% survival rate after lethal challenge when administered in a homologous two-dose regimen. Importantly, when given in a heterologous prime-boost vaccination scheme, in which vaccination with the initial chimeric virus was followed by a protein boost with the envelope protein domain III (EDIII), 100% of the mice were protected without showing any signs of morbidity. Combinations of this live-attenuated chimeric YFV-17D-POWV vaccine candidate with an EDIII protein boost warrant further studies for the development of an effective vaccine strategy for the prevention of POWV disease.

Enhancement of Vaccine-Induced T-Cell Responses by PD-L1 Blockade in Calves

Interactions between programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) cause functional exhaustion of T cells by inducing inhibitory signals, thereby attenuating effector functions of T cells. We have developed an anti-bovine PD-L1 blocking antibody (Ab) and have demonstrated that blockade of the interaction between PD-1 and PD-L1 reactivates T-cell responses in cattle. In the present study, we examined the potential utility of PD-1/PD-L1-targeted immunotherapy in enhancing T-cell responses to vaccination. Calves were inoculated with a hexavalent live-attenuated viral vaccine against bovine respiratory infections in combination with treatment with an anti-PD-L1 Ab. The expression kinetics of PD-1 in T cells and T-cell responses to viral antigens were measured before and after vaccination to evaluate the adjuvant effect of anti-PD-L1 Ab. PD-1 expression was upregulated in vaccinated calves after the administration of a booster vaccination. The activation status of CD4+, CD8+, and γδTCR+ T cells was enhanced by the combination of vaccination and PD-L1 blockade. In addition, IFN-γ responses to viral antigens were increased following combinatorial vaccination with PD-L1 blockade. In conclusion, the blockade of the PD-1/PD-L1 interaction enhances T-cell responses induced by vaccination in cattle, indicating the potential utility of anti-PD-L1 Ab in improving the efficacy of current vaccination programs.

Status of Herpes Zoster and Herpes Zoster Vaccines in 2023: A position paper.

Herpes zoster infection (HZ) is an important public health problem due to its high incidence and frequent complications, especially post-herpetic neuropathy . The incidence of HZ increases with age and is more frequent in immunocompromised patients. It is estimated that at least 60,000 people develop HZ each year in Spain. The usual forms of HZ are so clinically characteristic that they do not usually require microbiological confirmation, which is reserved for cases without cutaneous manifestations or with atypical presentation. There are currently two vaccines approved by the regulatory agencies and marketed in Spain to prevent the onset of HZ and its complications. The first (Zostavax®) was marketed by the company MSD and licensed in Europe in 2006 and is a live attenuated virus vaccine that is administered in a single dose, while the second (Shingrix®) is a recombinant vaccine, marketed in 2017 and requires two doses. While the former cannot be administered to immunocompromised persons, the latter can be prescribed to any group of adults. The criteria for the indication and financing of these vaccines have not been uniform in the various autonomous communities of Spain. These and other aspects of HZ have been discussed by a group of experts from the Illustrious Official College of Physicians of Madrid (ICOMEM) whose criteria and opinions are included in this paper.

Maternal antibodies induced by a live attenuated vaccine protect neonatal mice from cytomegalovirus

Human cytomegalovirus (HCMV) frequently causes congenital infections, resulting in birth defects and developmental disorders. A vaccine is needed, but unavailable. We analyzed the potential of CMV mutants, lacking their STAT2 antagonists to serve as live attenuated vaccine viruses in mice. Infections with attenuated viruses elicited strong ELISA-reactive binding IgG responses and induced neutralizing antibodies as well as antibodies stimulating cellular Fcγ receptors, including the antibody-dependent cellular cytotoxicity (ADCC)-eliciting receptors FcγRIII/CD16 and FcγRIV. Accordingly, vaccinated mice were fully protected against challenge infections. Female mice vaccinated prior to gestation transmitted CMV-specific IgG to their offspring, which protected the progeny from perinatal infections in a mouse model for congenital CMV disease. To define the role of maternal antibodies, female mice either capable or incapable of producing antibodies were vaccinated and subsequently bred to males of the opposite genotype. Challenge infections of the genotypically identical F1 generation revealed the indispensability of maternal antibodies for vaccine-induced protection against cytomegaloviruses.

A Monovalent Mt10-CVB3 Vaccine Prevents CVB4-Accelerated Type 1 Diabetes in NOD Mice.

Enteroviruses, which include Coxsackieviruses, are a common cause of virus infections in humans, and multiple serotypes of the group B Coxsackievirus (CVB) can induce similar diseases. No vaccines are currently available to prevent CVB infections because developing serotype-specific vaccines is not practical. Thus, developing a vaccine that induces protective immune responses for multiple serotypes is desired. In that direction, we created a live-attenuated CVB3 vaccine virus, designated mutant (Mt)10, that offers protection against myocarditis and pancreatitis induced by CVB3 and CVB4 in disease-susceptible A/J mice. Here, we report that the Mt10 vaccine protected against CVB4-triggered type 1 diabetes (T1D) in non-obese diabetic (NOD) mice but the expected subsequent development of spontaneous T1D in these genetically predisposed NOD mice was not altered. We noted that Mt10 vaccine induced significant amounts of neutralizing antibodies, predominantly of the IgG2c isotype, and the virus was not detected in vaccine-challenged animals. Furthermore, monitoring blood glucose levels-and to a lesser extent, insulin antibodies-was found to be helpful in predicting vaccine responses. Taken together, our data suggest that the monovalent Mt10 vaccine has the potential to prevent infections caused by multiple CVB serotypes, as we have demonstrated in various pre-clinical models.

572. Adverse Events Following Live Immunization in Patients with DiGeorge Syndrome: A Retrospective, Single Center Study in Korea

Abstract Background DiGeorge syndrome (DGS) is a syndrome accompanied by congenital heart defect, hypoparathyroidism and immunodeficiency of varying severity. Live vaccination is generally contraindicated in patients with DGS. However, in real clinical practice, there are cases in which live vaccines are immunized before the diagnosis of DGS or are incidentally immunized. We collected these cases and investigated adverse events (AEs), especially infections caused by the vaccine strains. Methods This retrospective study included all patients diagnosed with DGS at Severance Hospital Seoul, Korea, between November 2005 and June 2021. We extracted patients with ICD-10 code (D82.1) and then excluded subjects without genetic confirm. According to the immune status, subjects were categorized into three groups: group A [CD3 &amp;lt; 500 or CD8 &amp;lt; 200 (cells/mm3)], group B [CD3 ≥500 and CD8 ≥ 200 (cells/mm3)] and group C (unknown). Results Of a total 94 DGS patients, approximately 40% of subjects (38/94) underwent immunological test, of which 21% (8/38) belonged to group A and 79% (30/38) were in group B. Approximately 80% of study subjects (73/94) had a record of at least one live vaccination. By vaccine type, measles-mumps-rubella accounted for the most at 70% (66/94), followed by varicella, bacillus Calmette–Guérin, rotavirus, and live-attenuated Japanese encephalitis virus vaccine. A total of 50 AEs were observed (Figure 1): fever (n=29), URI (n=9), diarrhea (n=4), rash (n=3), thrombocytopenia (n=3), injection site pus (n=1) and febrile convulsion (n=1). Among them 26% (13/50) occurred in group A and no significant difference in the incidence rate of AEs between group A and B was observed (P = 0.14). Six cases of them turned out to be consistent with live vaccination by WHO 2009 causality analysis. Moreover, there were no serious reactions, including ICU hospitalization or death, and there was no emergence of disease caused by vaccine strains. Conclusion Our data show that live vaccines were often given without immunologic screening and generally well tolerated in our study population. Disclosures All Authors: No reported disclosures.

RARE CASE OF HOMOZYGOUS IFNAR1 DEFICIENCY IN A SAMOAN CHILD WITH DISSEMINATED VARICELLA AFTER VACCINATION

<h3>Introduction</h3> Autosomal recessive interferon alpha/beta receptor 1 (IFNAR1) deficiency increases susceptibility to live-attenuated vaccines and wild-type viruses. Currently 16 cases, half with Polynesian ancestry have been reported since the discovery in 2019. Most cases present with severe MMR or yellow fever vaccine-related disease. Some cases report severe SARS-CoV-2, herpes simplex, and enterovirus. Varicella vaccine-related disease has been hypothesized but not previously reported. <h3>Case Description</h3> A pediatric Samoan girl with congenital cardiac anomaly, otherwise healthy until receiving Varicella and MMR vaccines at 12 months. Two weeks later with presumed incomplete Kawasaki Disease with 10-day fever, red lips, and maculopapular rash, given IVIG and infliximab; also, positive SARS-CoV-2 PCR and IgG that admission. Developed diffuse vesicular rash 3 weeks after vaccination requiring re-admission for disseminated varicella. At 14 months, admitted again for acute respiratory failure with viral pericarditis, positive for rhinovirus/enterovirus on respiratory viral panel and varicella serum PCR. Samoan parents are first-degree cousins and her stillborn sister had significant homozygosity on genetic evaluation. Normal lymphocyte subsets, normal mitogen proliferation, absent antigen proliferation in vitro, and normal NK function. Intact humoral immunity. Primary immunodeficiency disease panel identified homozygous pathogenic variant in IFNAR1. Future live viral vaccines contraindicated. Managed with acyclovir with return to baseline. <h3>Discussion</h3> This case demonstrates a novel finding of homozygous IFNAR1 deficiency predisposing to disseminated varicella after vaccination. TNF inhibition may have also contributed. IFNAR1 deficiency should be considered in patients with severe varicella or other severe viral illnesses, especially after live-attenuated viral vaccines in those of Polynesian ancestry.

A live single-cycle RSV vaccine expressing prefusion F protein

Live-attenuated Respiratory syncytial virus (RSV) vaccines given intranasally have potential to provide comprehensive protection, including lung-resident immunity. It has however proven challenging to impart both sufficient safety and efficacy in a vaccine. To achieve the latter, we used a trans-complementing approach to generate live single-cycle RSV vaccines expressing the prefusion form (preF) of the viral fusion protein (F), either membrane-anchored or secreted. Both viruses were tested for their ability to induce a protective immune response in mice after intranasal prime-boost vaccination. The secreted preF vaccine failed to induce a protective response. The anchored preF vaccine induced anti-preF antibodies and antiviral T cells, and protected mice from lung pathology and viral shedding after challenge. Neither vaccine induced anti-G antibodies, for reasons unknown. In spite of the latter and single-cycle replication, the membrane-anchored preF vaccine was protective and demonstrates potential for development of an efficacious live vaccine with a stable safety phenotype.

Active Postlicensure Safety Surveillance for Recombinant Zoster Vaccine Using Electronic Health Record Data.

Recombinant zoster vaccine (RZV) (Shingrix; GlaxoSmithKline, Brentford, United Kingdom) is an adjuvanted glycoprotein vaccine that was licensed in 2017 to prevent herpes zoster (shingles) and its complications in older adults. In this prospective, postlicensure Vaccine Safety Datalink study using electronic health records, we sequentially monitored a real-world population of adults aged ≥50 years who received care in multiple US Vaccine Safety Datalink health systems to identify potentially increased risks of 10 prespecified health outcomes, including stroke, anaphylaxis, and Guillain-Barré syndrome (GBS). Among 647,833 RZV doses administered from January 2018 through December 2019, we did not detect a sustained increased risk of any monitored outcome for RZV recipients relative to either historical (2013-2017) recipients of zoster vaccine live, a live attenuated virus vaccine (Zostavax; Merck & Co., Inc., Kenilworth, New Jersey), or contemporary non-RZV vaccine recipients who had an annual well-person visit during the 2018-2019 study period. We confirmed prelicensure trial findings of increased risks of systemic and local reactions following RZV. Our study provides additional reassurance about the overall safety of RZV. Despite a large sample, uncertainty remains regarding potential associations with GBS due to the limited number of confirmed GBS cases that were observed.