A multivalent #mRNA #vaccine elicits robust immune responses and confers #protection in a murine #model of #monkeypox virus infection

Abstract

Monkeypox virus (MPXV) has re-emerged globally since May 2022, posing a significant public health threat. To address this, we develop two multivalent mRNA vaccine candidates—AAL, encoding three MPXV antigens, and AALI, which combines AAL with an immune-enhancing IFN-α protein. Both vaccines are delivered via mannose-modified lipid nanoparticles to target dendritic cells. Here we show that these vaccines elicit strong antibody responses against vaccinia virus and multiple MPXV clades, induce robust memory B-cell and T-cell responses, and promote dendritic cell maturation. In mouse challenge models, both vaccines provide protection against clade IIb MPXV and vaccinia virus, significantly reducing viral loads and preventing lung damage. Immune profiling reveals enhanced B- and T-cell receptor diversity and distinct CDR3 motifs post-vaccination. These findings demonstrate the potential of using mRNA-based multivalent vaccines as an effective strategy for preventing mpox and related Orthopoxvirus infections.

Source: Nature Communications, https://www.nature.com/articles/s41467-025-61699-w

____

#Coronavirus Disease Research #References (by AMEDEO, August 9 '25)

 

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    JAMA

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Antimicrob Agents Chemother

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   PubMed         Abstract available
   
   

   
   BMC Pediatr

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    J Virol Methods

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    PLoS One

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    Virology

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#Sialic Acid #Receptors in #Human Mammary Tissue: Implications for #Infection with Novel #Influenza Strains

 

Abstract

Importance: 

Highly pathogenic avian influenza (HPAI) A H5N1 has been recognized for nearly three decades as a threat to avian species and as a virus with pandemic potential if spillover into human populations occurs. Recently the virus has evolved capacity to infect many mammalian species, including dairy cattle, increasing the risk for human exposure and the pandemic threat. Sialic acids (SA) serve as binding sites for influenza viruses. The distribution of SA determines infectivity of specific influenza viruses across species and tissue tropism. Hemagglutinin (HA) of human and swine adapted influenza viruses bind primarily to SA with α2,6-galactose linkages and avian influenza viruses preferentially bind to SA with α2,3-galactose linkages. Recently, the bovine udder was found to contain SA with α2,3 linkages which allow the H5N1 virus to bind to bovine udder epithelium and to infect milk. The distribution of SA receptors in the human mammary gland is unknown. 

Objective: 

Evaluate normal human mammary tissue for the presence of both human and avian SA receptors. 

Design: 

Retrospective evaluation of lectin binding to sialic acids in human mammary tissue. 

Setting: 

US academic health center. 

Participants: 

Specimens obtained from de-identified women with residual non-malignant tissue following breast surgery at the University of California, San Diego. 

Exposures: 

Lectin affinity-staining of human tissue for the presence of SA. 

Main Outcomes and Measures: 

Presence or absence of lectin staining. 

Results: 

All mammary tissue samples demonstrated lectin staining for both SA receptors with α2,6-galactose and α2,3-galactose linkages. 

Conclusions and Relevance: 

The presence of SA receptors that can bind HPAI A H5N1 in human mammary tissue indicates that human milk could be infected during severe avian influenza infection. Pandemic preparedness must prioritize mechanisms to protect the safety of human milk.

Competing Interest Statement

Dr. Byington has intellectual property in and receives royalties from BioFire (biomerieux) through the University of Utah. Dr. Byington is a member of the board of directors of Becton Dickinson.

Funding Statement

This study did not receive any funding

Source: MedRxIV, https://www.medrxiv.org/content/10.1101/2025.08.06.25333154v1

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Subtype-specific neutralizing #antibodies promote #antigenic #shift during #influenza virus co-infection

 

Abstract

Reassortment between different influenza strains occurs when they co-infect the same host cell. The emergence of a reassortant virus depends on both its intrinsic fitness and extrinsic factors, including pre-existing humoral immunity. The generation of pandemic strains, such as H2N2 and H3N2, and zoonotic influenza A viruses, like H5N6, H5N8, and H7N9, in birds is suggested to be the result of extensive selection by pre-existing antibodies. To further explore the role of humoral immunity in reassortment, we generated two divergent fluorescent protein-expressing viruses and used strain-specific and cross-reactive monoclonal antibodies (mAbs) to assess the impact of cross-immunity on reassortment. Our results indicate that all mAbs altered the genotypic diversity and significantly reduced the release of progeny virions in co-infected cells both in vitro and in vivo. Moreover, antibody transfer studies in mice revealed protection from challenge with divergent pathogenicity profiles. Notably, selection driven by a strain-specific mAb depended on its neutralizing specificity, whereas the selection driven by broadly reactive mAbs was independent of neutralization specificity. Our findings demonstrate that pre-existing neutralizing antibodies shape reassortment and that strain-specific neutralizing antibodies promote antigenic shift during co-infection, which is not the case for broadly cross-reactive antibodies that recognize influenza viruses from different subtypes.

Competing Interest Statement

The authors have declared no competing interest.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.08.08.669311v1

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#Cytokine Regulation of #Human #Antibody Responses to #Influenza #Vaccines

 

Abstract

Vaccine responses vary widely in human studies. Here we pooled data measuring 66 cytokines from 4 different inactivated influenza vaccine (IIV) cohorts over 5 seasons (N=581) and identified a significant correlation between baseline/day 0 serum IL-18 and IFN-β concentrations and the antibody response on day 28. We investigated this further in human tonsil and spleen organoids, and found that several cytokines, including multiple Type I IFNs (IFN-β and others), IL-21, IL-12, IL-10, but not IL-18 or its downstream Type II IFN (IFN-β), could adjuvant the IIV vaccine to enhance the antibody response. The live attenuated influenza vaccine (LAIV) induced a stronger antibody response than the inactivated one in organoids. Adding a single cytokine, IFN-β, recapitulated most of the live vaccine-specific cytokine activation program and increased the antibody response of the inactivated vaccine to that of the live vaccine. Thus, the human vaccinees and the organoid data showed that IFN-β is a natural adjuvant. Two other antibody-boosting cytokines, IL-12 and IL-21, were induced by LAIV but not by Type I IFNs, which suggested parallel regulatory pathways. Moreover, IL-21 mRNA lipid nanoparticles (LNPs) greatly augmented the quantity and breadth of antibody responses in a mouse model of IIV vaccination, while IFN-β LNPs enhanced durability. These findings identified parallel cytokine pathways regulating human vaccine responses and provide a rationale for using cytokines as adjuvants to mimic the effectiveness of live-attenuated vaccines- without the risk of side effects.

Competing Interest Statement

The authors have declared no competing interest.

Source: BioRxIV, https://www.biorxiv.org/content/10.1101/2025.08.07.668218v1

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History of Mass Transportation: The FS Ale 501 Electric Multiple Unit

 

De user:axpde - Opera propia, GFDL, https://commons.wikimedia.org/w/index.php?curid=11625891

Source: Wikipedia, https://it.wikipedia.org/wiki/Minuetto_(treno)

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A versatile #H5N1-VSV #platform for safe #influenza virus #research applications

 

ABSTRACT

The H5N1 strain of influenza A virus (IAV) continues to cause severe infections in a range of avian and mammalian species, including sporadic but concerning cases in humans. There is growing concern that circulating H5N1 strains could lead to widespread human outbreaks. Research with highly pathogenic H5N1 viruses is restricted to Biosafety Level 3 (BSL-3) laboratories. Vesicular stomatitis virus (VSV)-based vaccine vectors expressing heterologous viral proteins from Ebola, SARS-CoV-2, Lassa virus, etc., have previously been shown to be safe and effective in animal models and human clinical trials. Here, we report the development of a recombinant VSV expressing the hemagglutinin (HA) and neuraminidase (NA) genes of H5N1 IAV (H5N1-VSV), which serves as a versatile platform to study various aspects of H5N1 IAV biology. H5N1-VSV replicated robustly to titers comparable to those of the full H5N1 virus in multiple cell lines. In mice, H5N1-VSV vaccination was safe, elicited strong immunity, and conferred protection against a circulating H5N1 strain. Notably, we found that polymorphisms in antigenic site Sa of circulating strains emerged under immune selection pressure in cattle, resembling the evolution of pandemic IAV in humans. These findings suggest that H5N1-VSV can serve as a safe, adaptable platform for influenza research.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00975-25?af=R

____

#Inflammatory, transcriptomic, and #cell fate responses underlying the #mammalian #transmission of avian #influenza viruses

 

ABSTRACT

Airborne transmissibility of avian influenza viruses (AIVs) in humans is considered an essential component of their pandemic risk. Although several viral factors regulating airborne transmission (AT) have been delineated, it is not known what, if any, responses at the respiratory epithelia are determinants of AIV AT. Using responses in the ferret nasal epithelium to a panel of H1N1 AIVs, we describe host responses that segregate with AT phenotypes. AIV infection upregulated interferon alpha and gamma responses and IL-6 JAK-STAT signaling and downregulated oxidative phosphorylation. Single-cell transcriptomics revealed that cellular genotoxic stress and NF-kB, interferon, and cell fate pathways differentiated host responses to AIVs with different transmissibilities. These responses culminated in greater AIV antigen-containing exudate and debris in the respiratory spaces of the nasal epithelium of ferrets inoculated with AT AIVs. More abundant CMPK2, SP100, and CXCL10 transcription in infected epithelia was a hallmark of AT viruses. Overall, our study reveals host responses associated with AIV infection and transmission in the nasal epithelium, the determinant anatomical site of influenza virus transmission.

IMPORTANCE

Airborne transmission (AT) is a critical component of the pandemic risks posed by avian influenza A viruses (AIVs). However, the host responses ultimately dictating transmissibility elicited by AIVs in the upper respiratory tract of mammals, the determinant site of influenza virus AT, are largely unknown. We identified host responses in the nasal epithelium of the upper respiratory tract differentially expressed in response to infection by AIVs of different mammalian ATs. Our data indicate that a definable host response was associated with AT of AIVs. These data would serve as an important basis for future mechanistic studies of AIV zoonosis and potentially have implications for understanding the mechanisms of transmission of respiratory viruses between humans.

Source: Journal of Virology, https://journals.asm.org/doi/full/10.1128/jvi.00647-25?af=R

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#USA, #Wastewater Data for Avian #Influenza #H5 (#CDC, August 8 '25)

 

{Summary}

Time Period: July 27, 2025 - August 02, 2025

-- H5 Detection: 4 sites (0.9%)

-- No Detection: 430 sites (99.1%)

-- No samples in last week: 24 sites

(...)

Source: US Centers for Disease Control and Prevention, https://www.cdc.gov/nwss/rv/wwd-h5.html

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#India - High pathogenicity avian #influenza #H5N1 viruses (#poultry) (Inf. with) - Immediate notification

 

Two Poultry Farms in the Odisha State.

Source: WOAH, https://wahis.woah.org/#/in-review/6694

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Post-exposure #prophylaxis regimen of #rabies monoclonal #antibody and #vaccine in category 3 potential exposure patients ...

 

Summary

Background

Rabies is almost invariably fatal. A rabies monoclonal antibody (RmAb) was approved in India in 2016 for passive prophylaxis. This post-marketing study aimed to evaluate the long-term safety, immunogenicity, and efficacy of a post-exposure prophylaxis (PEP) regimen containing RmAb.

Methods

This phase 4, open-label, randomised, active-controlled study was conducted at 15 tertiary care hospitals in India. Patients aged 2 years or older with WHO category 3 rabies exposure by a suspected rabid animal were eligible if the exposure occurred less than 72 h before enrolment, or less than 24 h before enrolment for exposures to the face, neck, hand, or fingers. Participants were randomly assigned (3:1) to receive either RmAb (Rabishield; Serum Institute of India, Pune, India) plus a purified Vero cell rabies vaccine (PVRV; Rabivax-S) or equine rabies immunoglobulin (ERIG; Equirab) plus PVRV as PEP. In each treatment group, patients were further randomly assigned (1:1) to receive PVRV either intradermally or intramuscularly. Study group allocation was done using a permuted block design with random block sizes of eight. A central randomisation list was generated before the study start and randomisation was performed with an interactive web response system. Participants and site personnel were not masked to group assignment. RmAb (3·33 IU/kg) and ERIG (40 IU/kg) were infiltrated into and around the wounds only on day 0 as per WHO 2018 recommendations. PVRV was administered 1·0 mL intramuscularly (days 0, 3, 7, 14, and 28) or 0·1 mL plus 0·1 mL intradermally (days 0, 3, 7, and 28). The primary outcome was treatment-related serious adverse events up to 365 days after immunisation, analysed in the safety analysis set (all participants who received at least one dose of vaccine with treatment). Geometric mean concentrations of rabies virus neutralising antibody were measured in a subset of patients. This study is registered with Clinical Trial Registry–India (CTRI/2019/06/019622) and is completed.

Findings

4059 participants were enrolled between Aug 21, 2019, and March 31, 2022, and randomly assigned. A total of 3994 participants (3001 male, 993 female) were treated (2996 RmAb plus PVRV, 998 ERIG plus PVRV), of which 3622 (90·7%) participants completed the 1-year follow-up. 11 adverse events were considered causally related to RmAb plus PVRV and 17 were considered causally related to the ERIG plus PVRV regimen. Most adverse events were mild and transient. Seven serious adverse events occurred in the RmAb group and all were causally unrelated. One causally related serious adverse event was reported in the ERIG group. On day 14, the geometric mean concentrations increased to 16·05 IU/mL (95% CI 13·25–19·44) in the RmAb group and 13·48 IU/mL (9·51–19·11) in the ERIG group (point estimate 1·19 [95% CI 0·82–1·72]). No patient developed rabies during the 1-year follow-up period.

Interpretation

RmAb was safe and well tolerated and showed protective efficacy against rabies. A PEP regimen containing RmAb plus PVRV was immunogenic with long-term persistence of immune response.

Funding

Serum Institute of India.

Source: Lancet, https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)00735-4/abstract?rss=yes

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#MERS-related #coronavirus circulating in #pangolins exhibits strong fusogenicity in #human #cells and high sensitivity to fusion inhibitors

Highlights

• MjHKU4r-CoV-1 with high fusogenicity induces inflammatory responses in human cells

• 6-HB structure determination unveils MjHKU4r-S-mediated membrane fusion mechanism

• MjHKU4r-CoV-1 HR2 peptides exhibit potent activity by targeting viral HR1 domain

• Stapled peptide MjHKU4r-HR2P10 shows potent and broad-spectrum anti-CoV activity

Summary

Unlike preceding MERS-related coronaviruses, the recently identified MjHKU4r-CoV-1 strain can directly infect human cells. Nonetheless, its potential pathogenic attributes and underlying molecular mechanisms remain unclear. We find that MjHKU4r-CoV-1 induces significant inflammation, including interleukin (IL)-6 and tumor necrosis factor alpha (TNF-α), and exhibits pronounced fusogenicity mediated by its spike (S) protein, leading to extensive syncytium formation. This suggests the possibility that MjHKU4r-CoV-1 possesses strong pathogenic potential in humans. Further, we successfully reveal the molecular mechanism of MjHKU4r-S-driven membrane fusion by crystallizing the six-helix bundle (6-HB) structure, a fusion apparatus composed of HR1 and HR2 domains. Concurrently, we develop a series of peptide-based fusion inhibitors that target the viral HR1 domain to impede the formation of viral 6-HB. Among these fusion inhibitors, a stapled peptide, MjHKU4r-HR2P10, shows the most potent inhibitory activity against MjHKU4r-CoV-1, MERS-CoV, SARS-CoV-2, and HCoV-OC43 infections at nanomolar level and thus holds considerable promise for further development as effective antiviral agents in clinic.

Source: Cell Reports Medicine, https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00350-7?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS2666379125003507%3Fshowall%3Dtrue

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Highly conserved #Betacoronavirus #sequences are broadly recognized by #human T cells

Highlights

• Conserved T cell epitope regions elicit strong CD4+ and CD8+ T cell responses in SARS2-exposed

• CTERs enhance cross-reactivity across multiple Betacoronaviruses

• Targeting non-spike proteins expands immune breadth and HLA coverage

• Removing low population coverage regions preserves cross-reactivity

Summary

The COVID-19 pandemic highlighted the critical need for vaccine strategies capable of addressing emerging viral threats. Betacoronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome (MERS), and SARS-CoV-2, present significant pandemic risks due to their zoonotic potential and genetic diversity. T cell-mediated immunity has demonstrated durable responses and strong cross-reactivity, offering a promising avenue for achieving broad immunity within a viral family. In this study, we combined comprehensive epitope mapping with sequence conservation analyses to identify conserved T cell epitope regions (CTERs), which constitute 12% of the complete SARS-CoV-2 proteome. We showed that SARS-CoV-2 CTER-specific T cells cross-reactively recognize sequences from multiple Betacoronavirus subgenera. Importantly, incorporating CTERs from non-spike proteins significantly enhanced T cell cross-reactivity potential and human leukocyte antigen (HLA) coverage compared with T cells targeting only spike proteins. Our findings lay the groundwork for a multi-antigen vaccine strategy that includes non-spike proteins to expand cross-reactive immunity across a broader spectrum of Betacoronaviruses.

Source: Cell, https://www.cell.com/cell/fulltext/S0092-8674(25)00804-9?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867425008049%3Fshowall%3Dtrue

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#Italy, #WNV and #Usutu Virus Weekly #Surveillance #Bulletin No. 4, July 7 '25: 84 new confirmed cases (ISS)

{Summary}

-- Since the last update (July 31), eighty-four new confirmed cases of human infection with West Nile Virus have been reported. 

-- Since the start of epidemic season, there were 173 confirmed WNV cases, of which: 

- 72 were West Nile Neuroinvasive Disease (WNND): (2 in Piedmont, 2 Lombardy, 4 Veneto, 1 Friuli-Venezia Giulia, 2 Emilia-Romagna, 37 Latium, 21 Campania, 1 Basilicata, 1 Sardegna), 

- 14 were asymptomatic cases in blood donors, 

- 85 were West Nile Fever cases, 

- 1 was an asymptomatic case 

-- Among the confirmed cases, there were eleven fatalities: 1 in Piedmont, 4 Latium, 6 . 

- The case-fatality rate among WNND cases is at 15% (during 2018 season it was 20%, whereas in 2024 it was 14%). 

-- No new confirmed cases of Usutu Virus human infection have been reported during current surveillance week.

(...)

Source: High Institute of Health, https://www.epicentro.iss.it/westnile/bollettino/Bollettino_WND_2025_04.pdf

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Dynamics of endemic #virus re-emergence in #children in #USA following #COVID19 #pandemic (2022–23): a prospective, multicentre, longitudinal, immunoepidemiological surveillance study

Summary

Background

The Pandemic Response Repository through Microbial and Immune Surveillance and Epidemiology (PREMISE) programme was established to translate knowledge gained from global immunoepidemiological surveillance into a better understanding of population-level dynamics of emerging and re-emerging infections, as well as into the discovery and development of biomedical countermeasures against potential pandemic threats. As proof of principle for this approach, we conducted a longitudinal immunoepidemiological study in children in the USA, focusing on enterovirus D68 (EV-D68) infection dynamics but also capturing surveillance of a broad array of other endemic respiratory pathogens. Serendipitously, our sampling spanned the lifting of widespread COVID-19 non-pharmaceutical interventions (NPIs) in 2022–23, following a unique period during which virus exposure markedly diminished.

Methods

This prospective, multicentre, longitudinal, immunoepidemiological surveillance study enrolled children aged 10 years or younger and weighing at least 8 kg at three US university sites. Blood specimens collected from January to June, 2022 (visit 1; pre-enterovirus season), and from January to June, 2023 (visit 3; post-enterovirus season), were tested in a multiplex assay for antibody binding to EV-D68 (prespecified primary objective) and a panel of 15 other respiratory viruses (exploratory objectives), and for neutralising activity against EV-D68, enterovirus A71, and respiratory syncytial virus (RSV; for antibody binding assay validation). Respiratory mid-turbinate swabs collected from children with symptomatic illness who participated in symptom surveys during July–December, 2022 (visit 2; enterovirus season), underwent metagenomic sequencing for pathogen detection. Serological data for EV-D68 were incorporated into epidemiological models based on case data from national surveillance to predict future transmission dynamics.

Findings

Of 488 eligible children approached, 174, with a median age of 3·4 years (IQR 1·9–6·4), were enrolled and followed up longitudinally from January, 2022, to June, 2023. Three children withdrew before study completion and 51 were lost to follow-up between visits 1 and 3. 90 paired serological samples and 73 respiratory swabs were tested. Mean antibody binding and neutralisation titres against all viruses tested increased over the study period, most notably in younger children with lower initial titres. The highest exposure rates (seroconversion or antibody boosting) were seen with SARS-CoV-2 (51 [59%] of 87), EV-D68 (36 [41%] of 87), RSV (36 [41%] of 87), and influenza (35 [40%] of 87), whereas the pathogens most frequently detected by respiratory swab sequencing were EV-D68 (clade B3), rhinovirus A, and rhinovirus C (n=7 each). Incorporating EV-D68 serological data into epidemiological models resulted in an 82% reduction in the range of prediction errors and a 33% reduction in median prediction errors for longer-term EV-D68 circulation dynamics compared with national pathogen surveillance data alone.

Interpretation

In this study, we captured immunological evidence of endemic virus re-emergence in children following lifting of pandemic NPIs, which revealed high rates of exposure to endemic respiratory pathogens in a large group of seronegative, predominantly younger, children. This study demonstrates the feasibility and utility of immunoepidemiological surveillance to enable more precise and accurate modelling of pathogen circulation dynamics to predict and prepare for future waves of disease.

Funding

Intramural Research Program of the National Institute of Allergy and Infectious Diseases–Vaccine Research Center, and the National Cancer Institute, National Institutes of Health.

Source: Lancet Infectious Diseases, https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(25)00349-4/fulltext?rss=yes

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#Nipah virus #infection - #India (#WHO D.O.N., August 6 '25)

Situation at a glance

Between 17 May and 12 July 2025, the Information and Public Relations Department, Government of Kerala informed through a series of official press releases about four confirmed cases, including two deaths, due to Nipah virus (NiV) infection in two districts of Kerala State. 

NiV infection is a bat-borne disease transmitted to humans through infected animals (such as bats or pigs), contaminated food or, less commonly, through close contact with infected individuals. 

Since 1998 NiV outbreaks have been reported in Bangladesh, India, Malaysia, the Philippines, and Singapore. 

In India, NiV infections have occurred multiple times since 2001 with outbreaks in West Bengal State in 2001 and 2007, and in Kerala State regularly since 2018. 

Since 2018, Kerala has reported a total of nine NiV outbreaks. While the state has a strong healthcare system and improved infection control measures since 2023, it is advisable to maintain strong preparedness and surveillance efforts while ensuring continued care for patients. 

At the same time, States that may be at risk should be encouraged to continue strengthen their detection systems and response capacities. 

With no licensed vaccine or treatment available, public health efforts should focus on raising awareness of risk factors and promoting preventive measures to reduce exposure to the virus, and on early case detection supported by adequate intensive supportive care. 

Currently, the risk of international disease spread is considered low. There is no evidence of human-to-human transmission of NiV internationally in this event.

Description of the situation

Between 17 May and 12 July 2025, the Information and Public Relations Department, Government of Kerala through a series of official press releases informed about four confirmed NiV cases, including two deaths, due to NiV infection from two districts of Kerala State. 

Of the four cases, two were reported from Malappuram and two from Palakkad district. 

This marks the first-ever outbreak in Palakkad District. 

Of the four cases, one case was reported in May (with symptom onset in April) and three in July with symptom onset June (two cases), and July (one case).

The first patient was an adult woman from Malappuram district with symptom onset on 25 April.  The patient was admitted in critical condition to a local hospital in Malappuram with fever, cough, and respiratory distress due to worsening of symptoms. She was transferred to intensive care on 2 May due to acute encephalitis syndrome. Samples were collected and tested positive for NiV at Calicut Medical College on 6 May. Confirmatory testing was conducted by the National Institute of Virology, Pune, and results confirmed on 8 May.

The second patient, also an adult woman from Malappuram district developed symptoms on 23 June and died on 1 July. She visited multiple healthcare facilities, before being transferred to a government medical facility, where clinical suspicion of NiV led to sample collection and laboratory testing. 

The third patient is an adult woman from Palakkad district who developed symptoms on 25 June. She sought care at several healthcare facilities, before being admitted to a multi-specialty hospital, where she remains in critical condition on ventilator support. This is the first confirmed NiV case in Palakkad district. 

The fourth case was an adult male also from Palakkad district, who developed symptoms on 6 July 2025. He sought initial medical care on the same day, was admitted to a private hospital on 10 July, and transferred to a multi-specialty hospital on 11 July. On 12 July, he died and was confirmed with NiV infection. This is the second confirmed case in Palakkad district.  

The sources of infection of the cases remain under investigation. 

None of these cases appear to be linked to each other, suggesting independent spillover events from the natural reservoir. 

A significant presence of fruit bats, the known reservoir for NiV has been observed in the affected areas.

Epidemiology

NiV infection is a bat-borne zoonotic disease transmitted to humans through infected animals (such as bats or pigs), or food contaminated with saliva, urine, and excreta of infected animals. It can also be transmitted directly from person to person through close contact with an infected person (although less common). Fruit bats or flying foxes (Pteropus species) are the natural hosts for the virus.

The incubation period ranges on average from 4 to 14 days. However, an incubation period of up to 45 days has been reported once. Laboratory diagnosis of a patient with a clinical history of NiV infection can be made during the acute and convalescent phases of the disease by using a combination of tests. The main tests used are Reverse Transcription Polymerase Chain Reaction (RT-PCR) from bodily fluids and antibody detection via enzyme-linked immunosorbent assay (ELISA).

Symptoms range from acute respiratory infection and fatal encephalitis. Further information about NiV infection can be found here.

The case-fatality rates in outbreaks across Bangladesh, India, Malaysia, and Singapore typically range from 40% to 100%, depending on local capabilities for early detection and clinical management. Although candidate products are in development, there are no licensed vaccines or therapeutics available for the prevention or treatment of NiV infection.

Public health response

Several public health measures have been implemented by local authorities including:

-- The Kerala state health minister chaired an emergency meeting to assess the situation and confirmed that preventive measures have been strengthened in accordance with the established NiV protocol.  

-- As of 17 July, contact tracing is intensively implemented. A total of 723 individuals have been identified as contacts of confirmed Nipah virus (NiV) cases across several districts: Palakkad (394), Malappuram (212), Kozhikode (114), Ernakulam (2), and Thrissur (1).  

-- Based on an in-depth investigation, Kerala health authorities have released route maps for the movement of three confirmed NiV cases reported in July, to trace potential community exposures.  

-- Alerts have been issued by health authorities in Kozhikode, Malappuram, and Palakkad districts. In response, 26 special teams were deployed to carry out contact tracing, monitor symptoms among contacts and inform the public. 

-- Additionally, a special alert has been issued to hospitals in Kannur, Kozhikode, Malappuram, Palakkad, Thrissur and Wayanad districts, instructing them to remain vigilant and promptly report any suspected cases with NiV symptoms.  

-- The public has been advised to avoid non-essential visits to healthcare facilities to minimize the risk of transmission.

-- WHO is closely coordinating with the National Centre for Disease Control on One Health and capacity building for high threat pathogens including NiV.

WHO risk assessment

As of July 2025, a total of nine NiV outbreaks have been reported in Kerala State. Recent case numbers reported in Kerala State are consistent with trends observed in previous years and are therefore not entirely unexpected. 

However, they continue to highlight a localized risk associated with NiV in that area. 

At this time, the overall risk to the broader national and regional population remains low.  

The first outbreak was reported in 2018 (23 cases including confirmed and probable; CFR: 91%), followed by subsequent outbreaks in 2019 (a single case who survived), 2021 (one case; CFR: 100%), 2023 (six cases including two deaths; CFR: 33%), 2024 (two cases; CFR 100%), and 2025. 

So far in 2025, four confirmed cases of NiV, have been reported, all from Kerala State, with the symptom onset in April (one case), June (two cases) and July (one case).  

These recurrent spillover events highlight the ongoing risk of NiV in Kerala. In addition, studies indicated that fruit bats tested positive for NiV antibodies in several other Indian states, suggesting that NiV infection may potentially emerge in other States.  

Kerala State has a robust healthcare system. While nosocomial transmission was confirmed during the 2023 outbreak, the Infection Prevention and Control (IPC), and waste management practices have since been strengthened and audited.  

The sources of infection for the 2025 cases are yet to be confirmed. 

WHO advice

In the absence of a vaccine or licensed treatment available for NiV disease, the only way to reduce or prevent infection in people is by raising awareness of the risk factors and supporting people with measures they can take to reduce exposure to the virus. 

Case management should focus on the delivery of timely, supportive care and be supported by a good laboratory system. Intensive supportive care is recommended to treat severe respiratory and neurologic complications.  

Public health educational messages should focus on:

-- Reducing the risk of bat-to-human transmission

-- Efforts to prevent transmission should first focus on decreasing bat access to date palm sap and other fresh food products. Freshly collected date palm juice should be boiled, and fruits should be thoroughly washed and peeled before consumption. Fruits with signs of bat bites should be discarded. Areas where bats are known to roost should be avoided.

-- Reducing the risk of human-to-human transmission.

-- Close unprotected physical contact with NiV-infected people should be avoided. Regular hand washing should be carried out after caring for or visiting sick people.

-- Controlling infection in health care settings

-- Health-care workers caring for patients with suspected or confirmed infection, or handling specimens from them, should implement standard infection control precautions at all times. 

-- As human-to-human transmission has been reported, in particular in health-care settings, contact and droplet precautions should be used in addition to standard precautions. Airborne precautions may be required in certain circumstances.

-- Samples taken from people and animals with suspected NiV infection should be handled by trained staff working in suitably equipped laboratories.

-- WHO does not recommend any travel and/or trade restrictions toward India based on the currently available information.

Further information

- Department of Public Relations, Government of Kerala. https://www.prd.kerala.gov.in/ml/node/307801

- Directorate of Health Services, Kerala. IDSP Daily Report 1 August 2025. Thiruvananthapuram: DHS Kerala; 2025. Available from: https://dhs.kerala.gov.in/wp-content/uploads/2025/08/IDSP-Daily-Report-01.08.2025.pdf

- Information & Public Relations Department, Government of Kerala 29 May 2025. Relief in Nipah: A total of 114 people tested negative after the quarantine period of all those on the contact list was over. Available from: https://prd.kerala.gov.in/index.php/ml/node/300946

- Public Relations Department, Government of Kerala. Nipah virus infection updated official report, May 2025. Thiruvananthapuram: Government of Kerala; 2025 [cited 2025 May 12]. Available from: https://prd.kerala.gov.in/ml/node/297643

- Public Relations Department, Government of Kerala. Nipah virus infection updated official report, May 2025. Thiruvananthapuram: Government of Kerala; 2025 [cited 2025 May 12]. Available from: https://prd.kerala.gov.in/ml/node/297971

- Department of Public Relations, Government of Kerala. Confirmed Nipah Cases in Malappuram and Palakkad Districts [press release]. Thiruvananthapuram: DPR Kerala; 4 July 2025. Available from: https://www.prd.kerala.gov.in/ml/node/307104. 

- Department of Public Relations, Government of Kerala. Nipah Virus Infection: Health Department Intensifies Surveillance and Containment Measures [press release]. Thiruvananthapuram: DPR Kerala; 2 July 2025. Available from: https://www.prd.kerala.gov.in/ml/node/306853. 

- Department of Public Relations, Government of Kerala. Health Department Issues Nipah Virus Alert in Palakkad and Malappuram [press release]. Thiruvananthapuram: DPR Kerala; 1 July 2025. Available from: https://www.prd.kerala.gov.in/ml/node/306653. 

- Department of Public Relations, Government of Kerala. A total of 499 people are on the Nipah contact list; 10 July. https://www.prd.kerala.gov.in/ml/node/307528 

- Department of Public Relations, Government of Kerala. A total of 609 people are on the Nipah contact list in the state; 14 July https://www.prd.kerala.gov.in/ml/node/307873 

- Department of Public Relations, Government of Kerala; 17 July: https://www.prd.kerala.gov.in/ml/node/308413

- Department of Public Relations, Government of Kerala. High-level meeting convened in connection with the spread of Nipah virus [press release]. Thiruvananthapuram: DPR Kerala; 11 July 2025. Available from: https://prd.kerala.gov.in/ml/node/307707 

- World Health Organization, Regional Office for South-East Asia. Regional strategy for the prevention and control of Nipah virus infection: 2023 2030. New Delhi: WHO SEARO; 2023. Available from: https://www.who.int/publications/i/item/9789290210849 

- World Health Organization. Technical brief: Enhancing readiness for a Nipah virus event in countries not reporting a Nipah virus event: interim document. Geneva: WHO; 2024 Feb. Available from: https://www.who.int/publications/i/item/9789290211273 

- World Health Organization. Nipah virus [Fact sheet]. Geneva: WHO; 2018. Available from: https://www.who.int/news-room/fact-sheets/detail/nipah-virus 

- 10th edition, Epidemiological Bulletin WHO Health Emergencies Programme WHO Regional Office for South-East Asia , 21 May 2025 Reporting period: 05 - 18 May 2025 Available from: https://www.who.int/southeastasia/publications/i/item/9789290220831

Citable reference: World Health Organization (6 August 2025). Disease Outbreak News; Nipah virus infection – India. Available at: https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON577

Source: World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2025-DON577

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