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February 2025  The development of influenza candidate vaccine viruses (CVVs),  coordinated by WHO, remains an essential component of the overall global  strategy for influenza pandemic preparedness . Selection and development of  CVVs are the first steps towards timely vaccine production and do not imply a  recommendation for initiating manufacture. National authorities may consider the  use of 1 or more of these CVVs for pilot lot vaccine production, clinical trials and  other pandemic preparedness purposes based on their assessment of public health  risk and need. Zoonotic influenza viruses continue to be identified  and evolve both antigenically and genetically, leading to the need for additional  CVVs for pandemic preparedness purposes. Changes in the antigenic and genetic  characteristics of these viruses relative to existing CVVs and their potential risks  to public health justify the need to develop new CVVs. This docume...

Abstract The ongoing panzootic of highly pathogenic avian influenza (HPAI) H5 clade 2.3.4.4b has caused widespread poultry mortality and raised concerns about zoonotic pandemics and wildlife conservation . France recently adopted a preventive vaccination strategy , vaccinating domestic ducks with inactivated and mRNA vaccines . This study evaluates the impact of this campaign on reducing HPAI H5 outbreaks. Using predictive modeling based on previous outbreak data, the expected number of outbreaks in 2023-24 without vaccination was significantly higher than the observed cases, indicating a 95.9% reduction attributable to vaccination . These findings suggest that vaccination effectively mitigated the HPAI H5 outbreak in France. Source: BioRxIV,  https://www.biorxiv.org/content/10.1101/2024.08.28.609837v3 ____

Abstract The effectiveness of antivirals in mitigating influenza outbreaks depends on both their ability to reduce the number of infections and the risk of drug resistance. We extended a previously developed mathematical model to investigate the impact of mitigation strategies , including mono or combination antiviral treatment or chemoprophylaxis and vaccination , on influenza transmission dynamics. Our findings indicate that chemoprophylaxis is more effective than treatment in reducing influenza burden, except when the resistant strain has a high transmission rate, in which case chemoprophylaxis may trigger a resistance-driven secondary infection wave. Combination therapy considerably reduces resistance emergence with similar infection numbers as mono-therapy. Vaccination coverage of at least 80% is required to prevent outbreaks; otherwise, antivirals can contribute to outbreak control provided drug resistance emergence is low. This analysis could inform public health decision-making...

Summary Background More than 115 000 cases of mpox have been confirmed since the onset of a global outbreak in 2022. In addition to global transmission of clade II monkeypox virus (MPXV), the recent spread of clade I has caused a Public Health Emergency of International Concern . The third-generation smallpox vaccine modified vaccinia Ankara–Bavarian Nordic (MVA-BN) was recommended for at-risk populations in 2022, despite a scarcity of data on safety and effectiveness against mpox. Methods We did a prospective, multicentre, observational study, enrolling men who have sex with men and transgender people aged 18 years or older with changing sexual partners in Germany (Safety and Effectiveness of MVA-BN Vaccination Against MPXV Infection [SEMVAc]) between July 7, 2022, and Dec 31, 2023, evaluating safety and reactogenicity of one and two doses of subcutaneous MVA-BN. Vaccine effectiveness was estimated using risk ratios from the Kaplan–Meier estimator in an emulated retrospective target t...

{Summary} Pandemic influenza remains a significant global health threat, as signalled by the circulation and cross-species transmission of avian influenza A(H5N1) viruses from the clade 2.3.4.4b, including among dairy cattle in the USA since 2024. Although most of the reported human infections from the USA so far1,2 have been mild, the virus can change its profile rapidly. To reduce mortality and morbidity from influenza in humans, vaccines remain the most important intervention. (...) Source: Lancet Respiratory Medicine,  https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(25)00052-9/fulltext?rss=yes ____

ABSTRACT The evolution of the antibody response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is impacted by the nature and number of antigenic exposures . First-generation coronavirus disease 2019 (COVID-19) vaccines encoded an ancestral spike protein . Updated bivalent vaccines and breakthrough infections have shaped the intricate diversity of the polyclonal antibody response and specificity of individual antibody clones. We and others previously showed that bivalent vaccines containing the ancestral and Omicron (BA.5) spikes induce high levels of cross-reactive antibodies but undetectable BA.5-specific antibodies in serum. Here, we assessed sera collected before as well as 1 and 3 months following administration of an updated XBB.1.5 monovalent vaccine to individuals with diverse infection and vaccination histories. Vaccination increased neutralization against recent variants of concern , including HV.1, JN.1 , and the vaccine-homologous XBB.1.5. Antibody bindi...

The World Health Organization (WHO) today announced the recommendations for the viral composition of influenza vaccines for the 2025-2026 influenza season in the northern hemisphere.  The announcement was made at an information session at the end of a 4-day meeting on the Composition of Influenza Virus Vaccines, a meeting that is held twice annually.  WHO organizes these consultations with an advisory group of experts gathered from WHO Collaborating Centres and WHO Essential Regulatory Laboratories to analyse influenza virus surveillance data generated by the WHO Global Influenza Surveillance and Response System (GISRS).  The recommendations issued are used by the national vaccine regulatory agencies and pharmaceutical companies to develop, produce, and license influenza vaccines for the following influenza season.  The periodic update of viruses contained in influenza vaccines is necessary for the vaccines to be effective due to the constant evolving nature of influ...

Abstract Influenza virus neuraminidase (NA) has emerged as a promising vaccine candidate due to its relatively stable antigenic structure and the ability of NA-specific antibodies to provide cross-protection within influenza virus subtypes . Since the influenza virus causes respiratory infections in humans, developing mucosal vaccines to protect the entry site of the virus is of high importance. Recombinant NA requires adjuvants to induce a protective immune response after mucosal administration. In the current study, we analyze the immunogenicity and protective efficacy of a recombinant NA-based influenza virus vaccine administered intranasally in combination with adjuvants consisting of outer membrane proteins from Neisseria meningitidis complexed with exogenous lipopolysaccharides (LPS) from Shigella flexneri or endogenous LPS from N. meningitidis. We evaluated the local and systemic humoral and cellular immune responses to adjuvanted recombinant N1 NA , analyzing the dynamics of lo...

The Texas Department of State Health Services is reporting the first death from measles in the ongoing outbreak in the South Plains and Panhandle regions.  The school-aged child who was not vaccinated was hospitalized in Lubbock last week and tested positive for measles. As of Feb. 25, 124 cases of measles have been confirmed in the outbreak since late January. Most of the cases are in children . Eighteen people have been hospitalized over the course of the outbreak. Measles is a highly contagious respiratory illness , which can cause life-threatening illness to anyone who is not protected against the virus. During a measles outbreak, about one in five people who get sick will need hospital care and one in 20 will develop pneumonia. Rarely, measles can lead to swelling of the brain and death. It can also cause pregnancy complications, such as premature birth and babies with low birth weight. Measles can be transmitted by direct contact with infectious droplets or by airborne spread...

Abstract Antigenic variability among influenza virus strains poses a significant challenge to developing broadly protective , long-lasting vaccines . Current annual vaccines target specific strains, requiring accurate prediction for effective neutralization. Despite sequence diversity across phylogenetic groups, the hemagglutinin (HA) head domain's structure remains highly conserved. Utilizing this conservation, we designed cross-group chimeric HAs that combine antigenic surfaces from distant strains. By structure-guided transplantation of receptor-binding site (RBS) residues, we displayed an H3 RBS on an H1 HA scaffold . These chimeric immunogens elicit cross-group polyclonal responses capable of neutralizing both base and distal strains. Additionally, the chimeras integrate heterotrimeric immunogens, enhancing modular vaccine design. This approach enables the inclusion of diverse strain segments to generate broad polyclonal responses. In the future, such modular immunogens may se...

Abstract Since 2022, three cases of human infections of novel H3N8 avian influenza viruses (AIVs) have been confirmed in China . Given the potential for significant public health implications , the prompt detection and containment of the virus is particularly important. Comprehensive analyses were conducted of the complete viral gene sequences of five H3 subtype AIVs that were isolated from chickens, pigeons, and geese in live poultry markets in China in 2023. Four strains exhibited a high degree of homology with the H3N8 viruses responsible for human infections in 2022 and 2023. A subsequent study was conducted to investigate the pathogenicity differences among multiple subtypes of the H3 AIVs in chickens. The study revealed that all infected chickens exhibited clinical signs and viral shedding. Notably, two H3N8 viruses, which were highly homologous to human strains, demonstrated significant differences in adaptability to chickens. The goose-derived H3N5 strain displayed high adaptab...

Abstract Introduction Vaccination is a critical part of the response to an influenza pandemic . Future influenza pandemics will likely leverage existing production processes and manufacturing facilities for seasonal influenza to make pandemic vaccines. Therefore, pandemic influenza vaccine response is heavily dependent on seasonal influenza vaccine production capacity. Methods WHO monitors global vaccine production to inform pandemic preparedness by regularly surveying influenza vaccine manufacturers to estimate both seasonal and potential pandemic vaccine production capacity overall and by region, vaccine type, and manufacturing process. The last survey estimates were for 2019; here, we report updated estimates based on data from the 2023 survey and compare to estimates from previous surveys. Results Our analysis estimates that annual seasonal influenza vaccine production capacity has remained relatively stable since 2019 at 1.53 billion doses and pandemic vaccine capacity at 4.13 and...

Abstract In 2023, Finland faced an outbreak of highly pathogenic avian influenza caused by clade 2.3.4.4b A(H5N1) viruses , which spread from wild birds to fur farms . Vaccinations of individuals at-risk , such as fur and poultry farm workers , veterinarians, and laboratory workers , began in June 2024 using the MF59-adjuvanted inactivated (H5N8) vaccine manufactured by Seqirus (based on clade 2.3.4.4b A/Astrakhan/3212/2020). We investigated antibody responses following a two-dose vaccination regimen in 39 subjects. Vaccination induced comparable levels of functional antibodies both against the vaccine virus and two clade 2.3.4.4b viruses, either associated with outbreaks in fur animals in Finland or cattle in the United States . Upon two doses of the vaccine for previously unvaccinated people, the seroprotection rate against the vaccine virus was 83 % (95 % CI 70-97 %, titer ≥20) and 97 % (95 % CI 90-100 %, titer ≥40) using microneutralization or hemagglutinin inhibition assays , resp...

Abstract Vaccination is a common influenza A virus (IAV) control strategy for pigs. Vaccine efficacy depends on strain cross-protection and effective vaccination program implementation. We evaluated a multi-faceted IAV vaccination strategy which included (a) monthly surveillance of pigs at weaning , (b) selection of epidemiologically relevant strains from farms under surveillance, (c) updating IAV strains in custom-made vaccines, and (d) seasonal mass vaccination with custom-made vaccines given to sows in 35 farrow-to-wean farms within an integrated swine farm system. Reduction of IAV in pigs from vaccinated sows was determined by monthly monitoring of farms for 30 months by IAV rRT-PCR (PCR) testing of nasal wipes collected from litters of piglets at weaning. Hemagglutinin (HA) nucleotide and amino acid (AA) sequence homology of the circulating and vaccine strains was determined by pairwise alignment and AA comparison at antigenic sites. Of the 35 farms monitored, 28 (80%) tested posi...

{Excerpt} In response to the ongoing evolution of SARS-CoV-2 , vaccine manufacturers have released updated COVID-19 vaccines annually since 2022. For much of 2024, the global spread was dominated by the JN.1 lineage of viruses,1 which are antigenically quite distant from the XBB.1.5 variant that was used in the previous vaccine booster.2 In August 2024, the US Food and Drug Administration authorised two updated mRNA vaccines (Pfizer–BioNTech and Moderna) based on the spike sequence of KP.2 , a subvariant in the JN.1 lineage.3 In the UK and the EU, a KP.2-based mRNA vaccine (BioNTech) was also authorised later in the year.4,5 We have now provided the first indication of the acute boosting effect of updated KP.2 monovalent mRNA vaccines (KP.2 MV) on serum SARS-CoV-2 neutralising antibodies in humans. Since the authorisation of the updated vaccine boosters, SARS-CoV-2 has evolved beyond KP.2, with the subvariant KP.3.1.1 becoming dominant globally and the subvariant XEC now gaining tracti...

{Excerpt} In a global first, Uganda’s Ministry of Health, the World Health Organization (WHO) and other partners today launched a first ever vaccine trial for Ebola from the Sudan species of the virus, and at an unprecedented speed for a randomized vaccine trial in an emergency . The principal investigators from Makerere University and the Uganda Virus Research Institute (UVRI), with support from WHO and other partners, have worked tirelessly to get the trial ready in 4 days since the outbreak was confirmed on 30 January. It is the first trial to assess the clinical efficacy of a vaccine against Ebola disease due to Sudan virus . The speed was achieved through advanced research preparedness, while ensuring full compliance with national and international regulatory and ethical requirements. The candidate vaccine was donated by IAVI , with financial support from WHO, the Coalition for Epidemic Preparedness Innovations (CEPI), Canada’s International Development Research Centre (IDRC), and...

Abstract H1N1 influenza viruses are responsible for both seasonal and pandemic influenza . The continual antigenic shift and drift of these viruses highlight the urgent need for a universal influenza vaccine to elicit broadly neutralizing antibodies (bnAbs). Identification and characterization of bnAbs elicited in natural infection and immunization to influenza virus hemagglutinin (HA) can provide insights for development of a universal influenza vaccine. Here, we structurally and biophysically characterize four antibodies that bind to a conserved region on the HA membrane-proximal region known as the anchor epitope. Despite some diversity in their VH and VK genes, the antibodies interact with the HA through germline-encoded residues in HCDR2 and LCDR3. Somatic mutations on HCDR3 also contribute hydrophobic interactions with the conserved HA epitope. This convergent binding mode provides extensive neutralization breadth against H1N1 viruses and suggests possible countermeasures against...

Abstract Early investigation revealed a reduced risk of SARS-CoV-2 infection among social contacts of COVID-19 vaccinated individuals, referred to as indirect protection. However, indirect protection from SARS-CoV-2 infection-acquired immunity and its comparative strength and durability to vaccine-derived indirect protection in the current epidemiologic context of high levels of vaccination, prior infection, and novel variants are not well characterized. Here, we show that both vaccine-derived and infection-acquired immunity independently yield indirect protection to close social contacts with key differences in their strength and waning. Analyzing anonymized SARS-CoV-2 surveillance data from 9,625 residents in California state prisons from December 2021 to December 2022, we find that vaccine-derived indirect protection against Omicron SARS-CoV-2 infection is strongest within three months of COVID-19 vaccination [30% (95% confidence interval: 20–38%)] with subsequent modest protection....

ABSTRACT Current influenza vaccination approaches protect against specific viral strains, but do not consistently induce broad and long-lasting protection to the diversity of circulating influenza viruses. Single-cycle viruses delivered to the respiratory tract may offer a promising solution as they safely express a diverse array of viral antigens by undergoing just one round of cell infection in their host and stimulate broadly protective resident memory T-cell responses in the lung. We have previously developed a vaccine candidate called S-FLU , which is limited to a single cycle of infection by inactivation of the hemagglutinin signal sequence and induces a broadly cross-reactive T-cell response and antibodies to neuraminidase, but fails to induce neutralizing antibodies to hemagglutinin after intranasal administration. This study describes the development of CLEARFLU , a derivative of S-FLU, which is designed to add a neutralizing antibody response to hemagglutinin. In contrast to ...

Abstract Influenza vaccine effectiveness and immunogenicity can be compromised with repeated vaccination . We assessed immunological markers in a cohort of healthcare workers (HCW) from six public hospitals around Australia during 2020–2021. Sera were collected pre-vaccination and ~14 and ~180 days post-vaccination and assessed in haemagglutination inhibition assay against egg-grown vaccine and equivalent cell-grown viruses. Responses to vaccination were compared by the number of prior vaccinations. Baseline sera were available for 595 HCW in 2020 and 1031 in 2021. 5% had not been vaccinated during five years prior to enrolment and 55% had been vaccinated every year. Post-vaccination titres for all vaccine antigens were lowest among HCW vaccinated in all 5-prior years and highest among HCW with 0 or 1 prior vaccinations , even after adjustment. This was observed for both influenza A subtypes and was dependent on pre-vaccination titre. Expanded cohorts are needed to better understand ho...