Respiratory Syncytial Virus Vaccine Research Articles

Intranasal respiratory syncytial virus vaccine attenuated by codon-pair deoptimization of seven open reading frames is genetically stable and elicits mucosal and systemic immunity and protection against challenge virus replication in hamsters.

Respiratory syncytial virus (RSV) is the most important viral agent of severe pediatric respiratory illness worldwide, but there is no approved pediatric vaccine. Here, we describe the development of the live-attenuated RSV vaccine candidate Min AL as well as engineered derivatives. Min AL was attenuated by codon-pair deoptimization (CPD) of seven of the 11 RSV open reading frames (ORFs) (NS1, NS2, N, P, M, SH and L; 2,073 silent nucleotide substitutions in total). Min AL replicated efficiently in vitro at the permissive temperature of 32°C but was highly temperature sensitive (shut-off temperature of 36°C). When serially passaged at increasing temperatures, Min AL retained greater temperature sensitivity compared to previous candidates with fewer CPD ORFs. However, whole-genome deep-sequencing of passaged Min AL revealed mutations throughout its genome, most commonly missense mutations in the polymerase cofactor P and anti-termination transcription factor M2-1 (the latter was not CPD). Reintroduction of selected mutations into Min AL partially rescued its replication in vitro at temperatures up to 40°C, confirming their compensatory effect. These mutations restored the accumulation of positive-sense RNAs to wild-type (wt) RSV levels, suggesting increased activity by the viral transcriptase, whereas viral protein expression, RNA replication, and virus production were only partly rescued. In hamsters, Min AL and derivatives remained highly restricted in replication in the upper and lower airways, but induced serum IgG and IgA responses to the prefusion form of F (pre F) that were comparable to those induced by wt RSV, as well as robust mucosal and systemic IgG and IgA responses against RSV G. Min AL and derivatives were fully protective against challenge virus replication. The derivatives had increased genetic stability compared to Min AL. Thus, Min AL and derivatives with selected mutations are stable, attenuated, yet highly-immunogenic RSV vaccine candidates that are available for further evaluation.

Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.

Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.

Exacerbated lung inflammation in offspring with high maternal antibody levels following secondary RSV exposure.

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.

RSV Vaccination Intention Among People Who Are or Plan to Become Pregnant.

Respiratory syncytial virus (RSV) is a common pediatric infection, with young infants being at the highest risk of hospitalization and long-term sequela. New preventive agents have been recommended to prevent severe RSV illness in infants, including a vaccine administered during pregnancy. The current rates of recommended vaccination in pregnancy are suboptimal. Our objective was to characterize interest in RSV vaccination during pregnancy among people across the United States who were pregnant or planning to become pregnant. In March 2023, we conducted a national cross-sectional online survey of individuals 18 to 45 years old who were currently pregnant or trying to become pregnant on their perceptions of RSV-related illness and intentions to get vaccinated against RSV. We performed logistic regression analyses to determine the odds and predicted proportions of the likelihood of RSV vaccination during pregnancy, controlling for sociodemographic factors. Of 1619 completed surveys, 1528 were analyzed. 54% of respondents indicated that they were "very likely" to get vaccinated against RSV during pregnancy. The perception of RSV as a serious illness was the strongest predictor of vaccination likelihood. In the full regression model, predicted proportions of "very likely" to vaccinate against RSV followed a similar pattern (63% if RSV infection was perceived as serious and likely, 55% if serious and unlikely, 35% if not serious; P < .001). Raising awareness of RSV infection as likely and potentially serious for infants may be an influential component of targeted communications that promote RSV vaccine uptake during pregnancy.

Acute Cardiac Events in Hospitalized Older Adults With Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV) infection can cause severe respiratory illness in older adults. Less is known about the cardiac complications of RSV disease compared with those of influenza and SARS-CoV-2 infection. To describe the prevalence and severity of acute cardiac events during hospitalizations among adults aged 50 years or older with RSV infection. This cross-sectional study analyzed surveillance data from the RSV Hospitalization Surveillance Network, which conducts detailed medical record abstraction among hospitalized patients with RSV infection detected through clinician-directed laboratory testing. Cases of RSV infection in adults aged 50 years or older within 12 states over 5 RSV seasons (annually from 2014-2015 through 2017-2018 and 2022-2023) were examined to estimate the weighted period prevalence and 95% CIs of acute cardiac events. Acute cardiac events, identified by International Classification of Diseases, 9th Revision, Clinical Modification or International Statistical Classification of Diseases, Tenth Revision, Clinical Modification discharge codes, and discharge summary review. Severe disease outcomes, including intensive care unit (ICU) admission, receipt of invasive mechanical ventilation, or in-hospital death. Adjusted risk ratios (ARR) were calculated to compare severe outcomes among patients with and without acute cardiac events. The study included 6248 hospitalized adults (median [IQR] age, 72.7 [63.0-82.3] years; 59.6% female; 56.4% with underlying cardiovascular disease) with laboratory-confirmed RSV infection. The weighted estimated prevalence of experiencing a cardiac event was 22.4% (95% CI, 21.0%-23.7%). The weighted estimated prevalence was 15.8% (95% CI, 14.6%-17.0%) for acute heart failure, 7.5% (95% CI, 6.8%-8.3%) for acute ischemic heart disease, 1.3% (95% CI, 1.0%-1.7%) for hypertensive crisis, 1.1% (95% CI, 0.8%-1.4%) for ventricular tachycardia, and 0.6% (95% CI, 0.4%-0.8%) for cardiogenic shock. Adults with underlying cardiovascular disease had a greater risk of experiencing an acute cardiac event relative to those who did not (33.0% vs 8.5%; ARR, 3.51; 95% CI, 2.85-4.32). Among all hospitalized adults with RSV infection, 18.6% required ICU admission and 4.9% died during hospitalization. Compared with patients without an acute cardiac event, those who experienced an acute cardiac event had a greater risk of ICU admission (25.8% vs 16.5%; ARR, 1.54; 95% CI, 1.23-1.93) and in-hospital death (8.1% vs 4.0%; ARR, 1.77; 95% CI, 1.36-2.31). In this cross-sectional study over 5 RSV seasons, nearly one-quarter of hospitalized adults aged 50 years or older with RSV infection experienced an acute cardiac event (most frequently acute heart failure), including 1 in 12 adults (8.5%) with no documented underlying cardiovascular disease. The risk of severe outcomes was nearly twice as high in patients with acute cardiac events compared with patients who did not experience an acute cardiac event. These findings clarify the baseline epidemiology of potential cardiac complications of RSV infection prior to RSV vaccine availability.

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.

Mucosal immunization with a low-energy electron inactivated respiratory syncytial virus vaccine protects mice without Th2 immune bias.

The respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory tract infections associated with numerous hospitalizations. Recently, intramuscular (i.m.) vaccines against RSV have been approved for elderly and pregnant women. Noninvasive mucosal vaccination, e.g., by inhalation, offers an alternative against respiratory pathogens like RSV. Effective mucosal vaccines induce local immune responses, potentially resulting in the efficient and fast elimination of respiratory viruses after natural infection. To investigate this immune response to an RSV challenge, low-energy electron inactivated RSV (LEEI-RSV) was formulated with phosphatidylcholine-liposomes (PC-LEEI-RSV) or 1,2-dioleoyl-3-trimethylammonium-propane and 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DD-LEEI-RSV) for vaccination of mice intranasally. As controls, LEEI-RSV and formalin-inactivated-RSV (FI-RSV) were used via i.m. vaccination. The RSV-specific immunogenicity of the different vaccines and their protective efficacy were analyzed. RSV-specific IgA antibodies and a statistically significant reduction in viral load upon challenge were detected in mucosal DD-LEEI-RSV-vaccinated animals. Alhydrogel-adjuvanted LEEI-RSV i.m. showed a Th2-bias with enhanced IgE, eosinophils, and lung histopathology comparable to FI-RSV. These effects were absent when applying the mucosal vaccines highlighting the potential of DD-LEEI-RSV as an RSV vaccine candidate and the improved performance of this mucosal vaccine candidate.

Vaccines for Respiratory Syncytial Virus Prevention in Older Adults.

This review evaluates the efficacy and safety of novel respiratory syncytial virus (RSV) vaccines approved for adults aged 60 years and older. A literature search through February 27, 2024 was conducted using search terms, such as RSV, viral respiratory illness, vaccine, RSVpreF, RSVpreF3, Prefusion F, Abrysvo, and Arexvy. Data from primary literature and vaccine prescribing information were reviewed, encompassing evaluations of clinical pharmacology, efficacy, safety, adverse events, warnings, and precautions. The literature review process resulted in 10 articles included within this article's scope, including the results of 2 major phase III trials presented in detail. Two RSV vaccines, Respiratory Syncytial Virus Vaccine (recombinant [adjuvanted]; RSVpreF3-ASO1E, Arexvy) and Respiratory Syncytial Virus Vaccine (recombinant; RSVpreF, Abrysvo), approved for preventing RSV-associated lower respiratory tract disease (LRTD) in adults aged 60 years or older in the United States are discussed. Results from Phase III trials have demonstrated the efficacy of 1 dose of these vaccines in preventing RSV-associated LRTD across 2 RSV seasons. The Advisory Committee on Immunization Practices currently recommends use of these vaccines under shared clinical decision-making for adults aged 60 years or older. Most common adverse effects include injection site reactions (eg, site pain, redness, and swelling). Administration requires a single intramuscular injection of 0.5 mL, reconstituted prior to administration. The RSVpreF3-ASO1E and RSVpreF vaccines effectively prevent RSV-associated LRTD in adults aged 60 years and older.

Experimental trials of predicted CD4+ and CD8+ T-cell epitopes of respiratory syncytial virus.

Respiratory syncytial virus (RSV) is the most common cause of viral lower respiratory tract infections (LRTIs) in young children around the world and an important cause of LRTI in the elderly. The available treatments and FDA-approved vaccines for RSV only lessen the severity of the infection and are recommended for infants and elderly people. We focused on developing a broad-spectrum vaccine that activates the immune system to directly combat RSV. The objective of this study is to identify CD4+ and CD8+ T-cell epitopes using an immunoinformatics approach to develop RSV vaccines. The efficacy of these peptides was validated through in-vitro and in-vivo studies involving healthy and diseased animal models. For each major histocompatibility complex (MHC) class-I and II, we found three epitopes of RSV proteins including F, G, and SH with an antigenic score of >0.5 and a projected SVM score of <5. Experimental validation of these peptides on female BALB/c mice was conducted before and after infection with the RSV A2 line 19f. We found that the 3RVMHCI (CD8+) epitope of the F protein showed significant results of white blood cells (19.72 × 103 cells/μl), neutrophils (6.01 × 103 cells/μl), lymphocytes (12.98 × 103 cells/μl), IgG antibodies (36.9 µg/ml), IFN-γ (86.96 ng/L), and granzyme B (691.35 pg/ml) compared to control at the second booster dose of 10 µg. Similarly, 4RVMHCII (CD4+) of the F protein substantially induced white blood cells (27.08 × 103 cells/μl), neutrophils (6.58 × 103 cells/μl), lymphocytes (16.64 × 103 cells/μl), IgG antibodies (46.13 µg/ml), IFN-γ (96.45 ng/L), and granzyme B (675.09 pg/ml). In-vitro studies showed that 4RVMHCII produced a significant level of antibodies in sera on day 45 comparable to mice infected with the virus. 4RVMHCII also induced high IFN-γ and IL-2 secretions on the fourth day of the challenge compared to the preinfectional stage. In conclusion, epitopes of the F protein showed considerable immune response and are suitable for further validation.

Maternal awareness, acceptability and willingness towards respiratory syncytial virus (RSV) vaccination during pregnancy in Ireland.

Respiratory syncytial virus (RSV) is the world's leading cause of viral acute lower respiratory infections (ALRI) in infants. WHO has identified maternal RSV vaccination a priority and candidate vaccines are in development; however, vaccine hesitancy remains an impediment to successful implementation of maternal immunization. This study, the largest antenatal survey conducted to-date, aimed to examine maternal RSV awareness, likely acceptance of RSV vaccination in pregnancy, and attitudes to maternal vaccination. Pregnant women of all gestations attending antenatal clinic of a university maternity hospital in Ireland were invited to participate. An information leaflet provided, consent obtained, and survey administered examining RSV awareness, willingness to avail of antenatal RSV vaccination, factors influencing acceptability and preferred sources of assistance. Research Ethics Committee (REC) approval obtained, and general data protection regulation (GDPR) guidelines followed. 528 women completed the survey. A large proportion (75.6%) had never heard of RSV, yet 48.5% would still avail of a vaccine, 45.8% were undecided and only 5.3% would not. The main factor making vaccination acceptable to women (76.4%) was that it protects their infant from illness (p < .001, CV 0.336 for association with acceptance) and general practitioner (GP) was the preferred guidance source in decision-making (57.7%). Despite low levels of maternal awareness of RSV, pregnant women in Ireland are open to availing of antenatal vaccination. Maternal immunization strategies need to focus on infant's protection from RSV-associated ALRI along with vaccine safety, and build on an interdisciplinary collaboration of maternal, neonatal, primary care and public health services.

Top studies of 2023 relevant to primary care: From the PEER team.

To provide a summary of the noteworthy medical articles published in 2023 that are relevant to family physicians. Articles were chosen and ranked by the PEER (Patients, Experience, Evidence, Research) team, a group of primary care health professionals focused on evidence-based medicine. The selection process involved routine surveillance of tables of contents in high-impact medical journals and continuous monitoring of EvidenceAlerts. Articles were prioritized based on their direct applicability to and potential to influence primary care practice. Selected articles addressed various clinical areas of primary care. The topics included a comparison of a treat-to-target approach versus a high-intensity statins prescription for lipid management; semaglutide and its impact on cardiovascular outcomes; respiratory syncytial virus vaccine for older adults; chlorthalidone versus hydrochlorothiazide in preventing cardiovascular events; amitriptyline for irritable bowel syndrome; the role of opioids in acute back pain; safety of oral penicillin challenges in patients allergic to penicillin; spironolactone for facial acne; strategies to reverse frailty in older adults; and identifying the provider of chronic disease management. Two "up and coming" medications are also mentioned: retatrutide for weight loss and fezolinetant for vasomotor symptoms of menopause. Research published in 2023 yielded several high-quality articles with topics relevant to primary care, including cardiovascular care, irritable bowel syndrome, care of the elderly, and acne management.

Respiratory Syncytial Virus Vaccines: Analysis of Pre-Marketing Clinical Trials for Immunogenicity in the Population over 50 Years of Age.

Immunosenescence refers to age-related alterations in immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on the vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV) that include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 42. Our preliminary evaluation of published results and interim analyses of RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Public Health Impact of the Adjuvanted RSVPreF3 Vaccine for Respiratory Syncytial Virus Prevention Among Older Adults in the United States.

Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract disease in older adults, resulting in substantial morbidity and mortality. This study estimates the public health impact of vaccination with the adjuvanted RSVPreF3 vaccine among adults aged ≥ 60years in the United States (US). A static, multi-cohort Markov model was used to estimate RSV-related outcomes over a 3-year time horizon for scenarios with and without one-time RSV vaccination. The base-case analysis assumed the same vaccination coverage as for influenza vaccines, with key epidemiology and vaccine inputs obtained from the published literature and phase 3 clinical trial results for the adjuvanted RSVPreF3 vaccine. Model outcomes included the clinical burden of RSV (symptomatic RSV acute respiratory illness [RSV-ARI] cases [classified as upper or lower respiratory tract disease], pneumonia complications, and mortality) and RSV-related healthcare resource use (hospitalizations, emergency department visits, outpatient visits, and antibiotic prescriptions). In the base-case analysis, approximately 56.7 million adults aged ≥ 60years received the vaccine, resulting in 2,954,465 fewer symptomatic RSV-ARI cases over 3years compared with no vaccination, including 321,019 fewer X-ray confirmed pneumonia cases and 16,660 fewer RSV-related deaths. Vaccination also prevented a substantial number of RSV-related hospitalizations (203,891), emergency department visits (164,060), outpatient visits (1,577,586), and antibiotic prescriptions (1,343,915) over the 3-year period. A considerable public health impact was observed across a range of sensitivity analyses. These findings highlight the potential of the adjuvanted RSVPreF3 vaccine to substantially reduce RSV disease burden among US older adults aged ≥ 60years.

Neutralizing activity of anti-respiratory syncytial virus monoclonal antibody produced in Nicotiana benthamiana

ABSTRACT Respiratory syncytial virus (RSV) is a highly contagious virus that affects the lungs and respiratory passages of many vulnerable people. It is a leading cause of lower respiratory tract infections and clinical complications, particularly among infants and elderly. It can develop into serious complications such as pneumonia and bronchiolitis. The development of RSV vaccine or immunoprophylaxis remains highly active and a global health priority. Currently, GSK’s Arexvy™ vaccine is approved for the prevention of lower respiratory tract disease in older adults (>60 years). Palivizumab and currently nirsevimab are the approved monoclonal antibodies (mAbs) for RSV prevention in high-risk patients. Many studies are ongoing to develop additional therapeutic antibodies for preventing RSV infections among newborns and other susceptible groups. Recently, additional antibodies have been discovered and shown greater potential for development as therapeutic alternatives to palivizumab and nirsevimab. Plant expression platforms have proven successful in producing recombinant proteins, including antibodies, offering a potential cost-effective alternative to mammalian expression platforms. Hence in this study, an attempt was made to use a plant expression platform to produce two anti-RSV fusion (F) mAbs 5C4 and CR9501. The heavy-chain and light-chain sequences of both these antibodies were transiently expressed in Nicotiana benthamiana plants using a geminiviral vector and then purified using single-step protein A affinity column chromatography. Both these plant-produced mAbs showed specific binding to the RSV fusion protein and demonstrate effective viral neutralization activity in vitro. These preliminary findings suggest that plant-produced anti-RSV mAbs are able to neutralize RSV in vitro.

Benefit of noninvasive vagus nerve stimulation in vaccine optimization for young children

Whether it is mandatory to vaccinate young children against SARS-CoV-2 and respiratory syncytial virus (RSV) is still an ongoing topic of debate. Indeed, vaccine acceptance for young children is either too low (in the case of COVID-19) or, in some cases, unattainable (with the demand far exceeding the capacity of production in the case of RSV vaccines in some countries). In addition, while vaccines do confer immunity, they can be complicated by inflammatory reactions to the vaccine itself. This inflammatory response is controlled by the nervous system, specifically the vagus nerve. Vagal tone optimization in and of itself confers some level of protection against viral infections such as SARS-CoV-2 or RSV, but the degree of protection has not been adequately evaluated. Even though additional studies are needed to validate a strategy of vagal optimization as an alternative to or co-treatment with vaccines, studies of noninvasive vagus nerve stimulation should be supported by public health agencies as an adjunctive tool providing young children with safe, ready-to-use immunization and protection from vaccine reactions. This recommendation is based on scientific, epidemiological, ethical, and economic considerations.

RSV-related Community COPD Exacerbations and Novel Diagnostics: A Binational Prospective Cohort Study.

Respiratory syncytial virus (RSV) is a common global respiratory virus increasingly recognized as a major pathogen in frail older adults and as a cause of chronic obstructive pulmonary disease (COPD) exacerbations. There is no single test for RSV in adults with acceptable diagnostic accuracy. Trials of RSV vaccines have recently shown excellent safety and efficacy against RSV in older adults; defining the frequency of RSV-related community infections and COPD exacerbations is important for vaccine deployment decisions. This prospective study aimed to establish the frequency of outpatient-managed RSV-related exacerbations of COPD in two well-characterized patient cohorts using a combination of diagnostic methods. Participants were recruited at specialist clinics in London, UK and Groningen, NL from 2017 and observed for three consecutive RSV seasons, during exacerbations and at least twice yearly. RSV infections were detected by reverse transcription-polymerase chain reaction (RT-PCR) and serologic testing. 377 patients with COPD attended 1,999 clinic visits and reported 310 exacerbations. There were 27 RSV-related exacerbations (8·7% of total); of these, seven were detected only on PCR, 16 only on serology and 4 by both methods. Increases in RSV specific N-protein antibody were as sensitive as antibody to pre-F or post-F for serodiagnosis of RSV related exacerbations. RSV is associated with 8.7% of outpatient managed COPD exacerbations in this study. Antibodies to RSV-N protein may have diagnostic value, potentially important in a vaccinated population. The introduction of vaccines that prevent RSV is expected to benefit patients with COPD.

RSV Prefusion F Protein–Based Maternal Vaccine — Preterm Birth and Other Outcomes

BackgroundVaccination against respiratory syncytial virus (RSV) during pregnancy may protect infants from RSV disease. Efficacy and safety data on a candidate RSV prefusion F protein–based maternal vaccine (RSVPreF3-Mat) are needed.MethodsWe conducted a phase 3 trial involving pregnant women 18 to 49 years of age to assess the efficacy and safety of RSVPreF3-Mat. The women were randomly assigned in a 2:1 ratio to receive RSVPreF3-Mat or placebo between 24 weeks 0 days and 34 weeks 0 days of gestation. The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract disease in infants from birth to 6 months of age and safety in infants from birth to 12 months of age. After the observation of a higher risk of preterm birth in the vaccine group than in the placebo group, enrollment and vaccination were stopped early, and exploratory analyses of the safety signal of preterm birth were performed.ResultsThe analyses included 5328 pregnant women and 5233 infants; the target enrollment of approximately 10,000 pregnant women and their infants was not reached because enrollment was stopped early. A total of 3426 infants in the vaccine group and 1711 infants in the placebo group were followed from birth to 6 months of age; 16 and 24 infants, respectively, had any medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 65.5%; 95% credible interval, 37.5 to 82.0), and 8 and 14, respectively, had severe medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 69.0%; 95% credible interval, 33.0 to 87.6). Preterm birth occurred in 6.8% of the infants (237 of 3494) in the vaccine group and in 4.9% of those (86 of 1739) in the placebo group (relative risk, 1.37; 95% confidence interval [CI], 1.08 to 1.74; P=0.01); neonatal death occurred in 0.4% (13 of 3494) and 0.2% (3 of 1739), respectively (relative risk, 2.16; 95% CI, 0.62 to 7.56; P=0.23), an imbalance probably attributable to the greater percentage of preterm births in the vaccine group. No other safety signal was observed.ConclusionsThe results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT04605159.)

Design and Preclinical Evaluation of a Nanoparticle Vaccine against Respiratory Syncytial Virus Based on the Attachment Protein G.

Human respiratory syncytial virus (RSV) poses a significant human health threat, particularly to infants and the elderly. While efficacious vaccines based on the F protein have recently received market authorization, uncertainties remain regarding the future need for vaccine updates to counteract potential viral drift. The attachment protein G has long been ignored as a vaccine target due to perceived non-essentiality and ineffective neutralization on immortalized cells. Here, we show strong G-based neutralization in fully differentiated human airway epithelial cell (hAEC) cultures that is comparable to F-based neutralization. Next, we designed an RSV vaccine component based on the central conserved domain (CCD) of G fused to self-assembling lumazine synthase (LS) nanoparticles from the thermophile Aquifex aeolicus as a multivalent antigen presentation scaffold. These nanoparticles, characterized by high particle expression and assembly through the introduction of N-linked glycans, showed exceptional thermal and storage stability and elicited potent RSV neutralizing antibodies in a mouse model. In conclusion, our results emphasize the pivotal role of RSV G in the viral lifecycle and culminate in a promising next-generation RSV vaccine candidate characterized by excellent manufacturability and immunogenic properties. This candidate could function independently or synergistically with current F-based vaccines.

Early Estimate of Nirsevimab Effectiveness for Prevention of Respiratory Syncytial Virus-Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season - New Vaccine Surveillance Network, October 2023-February 2024.

Respiratory syncytial virus (RSV) is the leading cause of hospitalization among infants in the United States. In August 2023, CDC's Advisory Committee on Immunization Practices recommended nirsevimab, a long-acting monoclonal antibody, for infants aged <8 months to protect against RSV-associated lower respiratory tract infection during their first RSV season and for children aged 8-19 months at increased risk for severe RSV disease. In phase 3 clinical trials, nirsevimab efficacy against RSV-associated lower respiratory tract infection with hospitalization was 81% (95% CI = 62%-90%) through 150 days after receipt; post-introduction effectiveness has not been assessed in the United States. In this analysis, the New Vaccine Surveillance Network evaluated nirsevimab effectiveness against RSV-associated hospitalization among infants in their first RSV season during October 1, 2023-February 29, 2024. Among 699 infants hospitalized with acute respiratory illness, 59 (8%) received nirsevimab ≥7 days before symptom onset. Nirsevimab effectiveness was 90% (95% CI = 75%-96%) against RSV-associated hospitalization with a median time from receipt to symptom onset of 45 days (IQR = 19-76 days). The number of infants who received nirsevimab was too low to stratify by duration from receipt; however, nirsevimab effectiveness is expected to decrease with increasing time after receipt because of antibody decay. Although nirsevimab uptake and the interval from receipt of nirsevimab were limited in this analysis, this early estimate supports the current nirsevimab recommendation for the prevention of severe RSV disease in infants. Infants should be protected by maternal RSV vaccination or infant receipt of nirsevimab.

Epidemiology and burden of respiratory syncytial virus in Italian adults: A systematic review and meta-analysis.

Respiratory syncytial virus (RSV) is a common respiratory pathogen not only in children, but also in adults. In view of a recent authorization of adult RSV vaccines in Italy, our research question was to quantify the epidemiology and burden of RSV in Italian adults. Observational studies on the epidemiology and clinical burden of laboratory-confirmed or record-coded RSV infection in Italian adults of any age were eligible. Studies with no separate data for Italian adults, modeling and other secondary publications were excluded. A literature search was performed in MEDLINE, Biological Abstracts, Global Health, Scopus and Web of Science on 22 November 2023. Critical appraisal was performed by means of a Joanna Briggs Institute checklist. Random-effects (RE) meta-analysis was performed to obtain pooled estimates and the observed heterogeneity was investigated by subgroup and meta-regression analyses. The protocol was prospectively registered (doi.org/10.17504/protocols.io.5qpvo32odv4o/v1). Thirty-five studies were identified, most of which had at least one possible quality concern. RSV seasonal attack rates ranged from 0.8 ‰ in community-dwelling older adults to 10.9% in hematological outpatients. In the RE model, 4.5% (95% CI: 3.2-5.9%) of respiratory samples tested positive for RSV. This positivity prevalence was higher in older adults (4.4%) than in working-age adults (3.5%) and in outpatient (4.9%) than inpatient (2.9%) settings. According to the meta-regression, study location and sample size were also significant predictors of RSV detection frequency. The pooled estimate of in-hospital mortality was as high as 7.2% (95% CI: 4.7-10.3%). Data on other indicators of the diseases burden, such as complication and hospitalization rates, were unavailable. RSV poses a measurable burden on Italian adults, especially those of older age and with some co-morbidities. However, several data on the natural history of RSV disease are missing and should be established by future large-scale studies.