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Authorization of the Matrix-M (MM)-adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization for malaria prevention in children are a milestone in the fight against malaria. Yet, our understanding of the innate and adaptive immune responses elicited by this vaccine remains limited. Here, we compared three clinically relevant adjuvants [3M-052 + aluminum hydroxide (Alum) (3M), a TLR7/8 agonist formulated in Alum; GLA-LSQ, a TLR4 agonist formulated in liposomes with QS-21; and MM, the now-approved adjuvant for R21] for their capacity to induce durable immune responses to R21 in macaques. R21 adjuvanted with 3M on a 0, 8, and 23-week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/MM vaccine administered using a 0-4-8-week regimen and persisted up to 72 weeks with a half-life of 337 days. A booster dose at 72 weeks induced a recall response similar to the R21/MM vaccination. In contrast, R21/GLA-LSQ immunization induced a lower, short-lived response at the dose used. Consistent with the durable serum antibody responses, MM and 3M induced long-lived plasma cells in the bone marrow and other tissues, including the spleen. Furthermore, whereas 3M stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, MM induced enhanced expression of interferon- and TH2-related signatures more highly after the booster vaccination. Collectively, these findings provide a resource on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M as another adjuvant for malarial vaccines.
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Adyuvantes Inmunológicos , Vacunas contra la Malaria , Animales , Vacunas contra la Malaria/inmunología , Adyuvantes Inmunológicos/farmacología , Macaca mulatta , Adyuvantes de Vacunas , Anticuerpos Antiprotozoarios/inmunología , Citocinas/metabolismoRESUMEN
Viral haemorrhagic fevers (VHF) pose a significant threat to human health. In recent years, VHF outbreaks caused by Ebola, Marburg and Lassa viruses have caused substantial morbidity and mortality in West and Central Africa. In 2022, an Ebola disease outbreak in Uganda caused by Sudan virus resulted in 164 cases with 55 deaths. In 2023, a Marburg disease outbreak was confirmed in Equatorial Guinea and Tanzania resulting in over 49 confirmed or suspected cases; 41 of which were fatal. There are no clearly defined correlates of protection against these VHF, impeding targeted vaccine development. Any vaccine developed should therefore induce strong and preferably long-lasting humoral and cellular immunity against these viruses. Ideally this immunity should also cross-protect against viral variants, which are known to circulate in animal reservoirs and cause human disease. We have utilized two viral vectored vaccine platforms, an adenovirus (ChAdOx1) and Modified Vaccinia Ankara (MVA), to develop a multi-pathogen vaccine regime against three filoviruses (Ebola virus, Sudan virus, Marburg virus) and an arenavirus (Lassa virus). These platform technologies have consistently demonstrated the capability to induce robust cellular and humoral antigen-specific immunity in humans, most recently in the rollout of the licensed ChAdOx1-nCoV19/AZD1222. Here, we show that our multi-pathogen vaccines elicit strong cellular and humoral immunity, induce a diverse range of chemokines and cytokines, and most importantly, confers protection after lethal Ebola virus, Sudan virus and Marburg virus challenges in a small animal model.
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Ebolavirus , Fiebre Hemorrágica Ebola , Fiebre de Lassa , Virus Lassa , Enfermedad del Virus de Marburg , Marburgvirus , Animales , Ratones , Ebolavirus/inmunología , Virus Lassa/inmunología , Marburgvirus/inmunología , Fiebre Hemorrágica Ebola/prevención & control , Fiebre Hemorrágica Ebola/inmunología , Fiebre de Lassa/inmunología , Fiebre de Lassa/prevención & control , Enfermedad del Virus de Marburg/inmunología , Enfermedad del Virus de Marburg/prevención & control , Vacunas Virales/inmunología , Humanos , Vacunación , Femenino , Anticuerpos Antivirales/inmunología , Inmunogenicidad Vacunal , Vacunas contra el Virus del Ébola/inmunologíaRESUMEN
Although licensed vaccines against influenza virus have been successful in reducing pathogen-mediated disease, they have been less effective at preventing viral infection of the airways and current seasonal updates to influenza vaccines do not always successfully accommodate viral drift. Most licensed influenza and recently licensed RSV vaccines are administered via the intramuscular route. Alternative immunisation strategies, such as intranasal vaccinations, and "prime-pull" regimens, may deliver a more sterilising form of protection against respiratory viruses. A bivalent ChAdOx1-based vaccine (ChAdOx1-NP + M1-RSVF) encoding conserved nucleoprotein and matrix 1 proteins from influenza A virus and a modified pre-fusion stabilised RSV A F protein, was designed, developed and tested in preclinical animal models. The aim was to induce broad, cross-protective tissue-resident T cells against heterotypic influenza viruses and neutralising antibodies against RSV in the respiratory mucosa and systemically. When administered via an intramuscular prime-intranasal boost (IM-IN) regimen in mice, superior protection was generated against challenge with either RSV A, Influenza A H3N2 or H1N1. These results support further clinical development of a pan influenza & RSV vaccine administered in a prime-pull regimen.
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Many vaccines, including those using recombinant antigen subunits, rely on adjuvant(s) to enhance the efficacy of the host immune responses. Among the few adjuvants clinically approved, QS-21, a saponin-based immunomodulatory molecule isolated from the tree bark of Quillaja saponaria (QS) is used in complex formulations in approved effective vaccines. High demand of the QS raw material as well as manufacturing scalability limitation has been barriers here. We report for the first-time successful plant cell culture production of QS-21 having structural, chemical, and biologic, properties similar to the bark extracted product. These data ensure QS-21 and related saponins are broadly available and accessible to drug developers.
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BACKGROUND: The tick-borne bunyavirus, Crimean-Congo Haemorrhagic Fever virus (CCHFV), can cause severe febrile illness in humans and has a wide geographic range that continues to expand due to tick migration. Currently, there are no licensed vaccines against CCHFV for widespread usage. METHODS: In this study, we describe the preclinical assessment of a chimpanzee adenoviral vectored vaccine (ChAdOx2 CCHF) which encodes the glycoprotein precursor (GPC) from CCHFV. FINDINGS: We demonstrate here that vaccination with ChAdOx2 CCHF induces both a humoral and cellular immune response in mice and 100% protection in a lethal CCHF challenge model. Delivery of the adenoviral vaccine in a heterologous vaccine regimen with a Modified Vaccinia Ankara vaccine (MVA CCHF) induces the highest levels of CCHFV-specific cell-mediated and antibody responses in mice. Histopathological examination and viral load analysis of the tissues of ChAdOx2 CCHF immunised mice reveals an absence of both microscopic changes and viral antigen associated with CCHF infection, further demonstrating protection against disease. INTERPRETATION: There is the continued need for an effective vaccine against CCHFV to protect humans from lethal haemorrhagic disease. Our findings support further development of the ChAd platform expressing the CCHFV GPC to seek an effective vaccine against CCHFV. FUNDING: This research was supported by funding from the Biotechnology and Biological Sciences Research Council (UKRI-BBSRC) [BB/R019991/1 and BB/T008784/1].
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Virus de la Fiebre Hemorrágica de Crimea-Congo , Fiebre Hemorrágica de Crimea , Vacunas Virales , Humanos , Animales , Ratones , Fiebre Hemorrágica de Crimea/prevención & control , Virus de la Fiebre Hemorrágica de Crimea-Congo/genética , Vacunación , Vectores Genéticos/genética , Virus VacciniaRESUMEN
Effective vaccines have reduced the morbidity and mortality caused by severe acute respiratory syndrome coronavirus-2 infection; however, the elderly remain the most at risk. Understanding how vaccines generate protective immunity and how these mechanisms change with age is key for informing future vaccine design. Cytotoxic CD8+ T cells are important for killing virally infected cells, and vaccines that induce antigen-specific CD8+ T cells in addition to humoral immunity provide an extra layer of immune protection. This is particularly important in cases where antibody titers are suboptimal, as can occur in older individuals. Here, we show that in aged mice, spike epitope-specific CD8+ T cells are generated in comparable numbers to younger animals after ChAdOx1 nCoV-19 vaccination, although phenotypic differences exist. This demonstrates that ChAdOx1 nCoV-19 elicits a good CD8+ T-cell response in older bodies, but that typical age-associated features are evident on these vaccine reactive T cells.
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Linfocitos T CD8-positivos , COVID-19 , Animales , Humanos , Ratones , ChAdOx1 nCoV-19 , COVID-19/prevención & control , Vacunación , Linfocitos T Citotóxicos , Anticuerpos AntiviralesRESUMEN
Emergence from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has been facilitated by the rollout of effective vaccines. Successful vaccines generate high-affinity plasma blasts and long-lived protective memory B cells. Here, we show a requirement for T follicular helper (Tfh) cells and the germinal center reaction for optimal serum antibody and memory B cell formation after ChAdOx1 nCoV-19 vaccination. We found that Tfh cells play an important role in expanding antigen-specific B cells while identifying Tfh-cell-dependent and -independent memory B cell subsets. Upon secondary vaccination, germinal center B cells generated during primary immunizations can be recalled as germinal center B cells again. Likewise, primary immunization GC-Tfh cells can be recalled as either Tfh or Th1 cells, highlighting the pluripotent nature of Tfh cell memory. This study demonstrates that ChAdOx1 nCoV-19-induced germinal centers are a critical source of humoral immunity.
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COVID-19 , Inmunidad Humoral , Humanos , ChAdOx1 nCoV-19 , Células B de Memoria , Células T Auxiliares Foliculares , Linfocitos T Colaboradores-Inductores , COVID-19/prevención & control , SARS-CoV-2 , Centro Germinal , Vacunación , Inmunización SecundariaRESUMEN
Traditional chemical adjuvants remain a practical means of enhancing the immunogenicity of vaccines. Nevertheless, it is recognized that increasing the immunogenicity of viral vectors is challenging. Recently, STING ligands have been shown to enhance the efficacy of different vaccine platforms, but their affectivity on viral-vectored vaccination has not been fully assessed. In this study we used a multi-pronged approach to shed light on the immunological properties and potential mechanisms of action of this type of adjuvant and focused our study on replication-deficient human adenovirus serotype 5 (AdHu5). When the STING ligand 2'3'-cGAMP was mixed with AdHu5, the adjuvant enhanced anti-vector immune responses while decreasing the transgene-specific CD8+ T cell response. Studies employing STING-knockout mice and a 2'3'-cGAMP inactive analogue confirmed the aforementioned effects were STING dependent. In vitro assays demonstrated 2'3'-cGAMP induced the production of IFN-ß which in turn negatively affected AdHu5 transgene expression and CD8+ T cell immunogenicity. In an effort to overcome the negative impact of early 2'3'-cGAMP signaling on AdHu5 transgene immunogenicity, we generated a bicistronic vector encoding the 2'3'-cGAMP together with a model antigen. Intracellular production of 2'3'-cGAMP after AdHu5 infection was able to enhance transgene-specific CD8+ T cell immunogenicity, although not to a level that would warrant progression of this adjuvant to clinical assessment. This work highlights the importance of timing of 2'3'-cGAMP administration when assessing its adjuvant capacity with different vaccine modalities.
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Adenovirus Humanos , Vacunas Virales , Adenovirus Humanos/genética , Adyuvantes Inmunológicos , Animales , Linfocitos T CD8-positivos , Vectores Genéticos/genética , Humanos , Ratones , Vacunación , Vacunas Virales/genéticaRESUMEN
ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenovirus-vectored vaccine encoding the spike (S) protein of SARS-CoV-2, based on the first published full-length sequence (Wuhan-1). AZD1222 has been shown to have 74% vaccine efficacy against symptomatic disease in clinical trials. However, variants of concern (VoCs) have been detected, with substitutions that are associated with a reduction in virus neutralizing antibody titer. Updating vaccines to include S proteins of VoCs may be beneficial, even though current real-world data is suggesting good efficacy following boosting with vaccines encoding the ancestral S protein. Using the Syrian hamster model, we evaluate the effect of a single dose of AZD2816, encoding the S protein of the Beta VoC, and efficacy of AZD1222/AZD2816 as a heterologous primary series against challenge with the Beta or Delta variant. Minimal to no viral sgRNA could be detected in lungs of vaccinated animals obtained at 3- or 5- days post inoculation, in contrast to lungs of control animals. In Omicron-challenged hamsters, a single dose of AZD2816 or AZD1222 reduced virus shedding. Thus, these vaccination regimens are protective against the Beta, Delta, and Omicron VoCs in the hamster model.
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COVID-19 , Vacunas Virales , Animales , Anticuerpos Antivirales , COVID-19/prevención & control , ChAdOx1 nCoV-19 , Cricetinae , Humanos , Mesocricetus , SARS-CoV-2RESUMEN
BACKGROUND: There is an ongoing global effort to design, manufacture, and clinically assess vaccines against SARS-CoV-2. Over the course of the ongoing pandemic a number of new SARS-CoV-2 virus isolates or variants of concern (VoC) have been identified containing mutations in key proteins. METHODS: In this study we describe the generation and preclinical assessment of a ChAdOx1-vectored vaccine (AZD2816) which expresses the spike protein of the Beta VoC (B.1.351). FINDINGS: We demonstrate that AZD2816 is immunogenic after a single dose. When AZD2816 is used as a booster dose in animals primed with a vaccine encoding the original spike protein (ChAdOx1 nCoV-19/ [AZD1222]), an increase in binding and neutralising antibodies against Beta (B.1.351), Gamma (P.1) and Delta (B.1.617.2) is observed following each additional dose. In addition, a strong and polyfunctional T cell response was measured all booster regimens. INTERPRETATION: Real world data is demonstrating that one or more doses of licensed SARS-CoV-2 vaccines confer reduced protection against hospitalisation and deaths caused by divergent VoC, including Omicron. Our data support the ongoing clinical development and testing of booster vaccines to increase immunity against highly mutated VoC. FUNDING: This research was funded by AstraZeneca with supporting funds from MRC and BBSRC.
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COVID-19 , SARS-CoV-2 , COVID-19/prevención & control , Vacunas contra la COVID-19 , ChAdOx1 nCoV-19 , Humanos , SARS-CoV-2/genéticaRESUMEN
Protection from liver-stage malaria requires high numbers of CD8+ T cells to find and kill Plasmodium-infected cells. A new malaria vaccine strategy, prime-target vaccination, involves sequential viral-vectored vaccination by intramuscular and intravenous routes to target cellular immunity to the liver. Liver tissue-resident memory (TRM) CD8+ T cells have been shown to be necessary and sufficient for protection against rodent malaria by this vaccine regimen. Ultimately, to most faithfully assess immunotherapeutic responses by these local, specialised, hepatic T cells, periodic liver sampling is necessary, however this is not feasible at large scales in human trials. Here, as part of a phase I/II P. falciparum challenge study of prime-target vaccination, we performed deep immune phenotyping, single-cell RNA-sequencing and kinetics of hepatic fine needle aspirates and peripheral blood samples to study liver CD8+ TRM cells and circulating counterparts. We found that while these peripheral 'TRM-like' cells differed to TRM cells in terms of previously described characteristics, they are similar phenotypically and indistinguishable in terms of key T cell residency transcriptional signatures. By exploring the heterogeneity among liver CD8+ TRM cells at single cell resolution we found two main subpopulations that each share expression profiles with blood T cells. Lastly, our work points towards the potential for using TRM-like cells as a correlate of protection by liver-stage malaria vaccines and, in particular, those adopting a prime-target approach. A simple and reproducible correlate of protection would be particularly valuable in trials of liver-stage malaria vaccines as they progress to phase III, large-scale testing in African infants. We provide a blueprint for understanding and monitoring liver TRM cells induced by a prime-target malaria vaccine approach.
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Vacunas contra la Malaria/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Vectores Genéticos , Hepatocitos/inmunología , Humanos , Inmunidad Celular , Memoria Inmunológica/inmunología , Hígado/inmunología , Malaria/inmunología , Plasmodium/inmunología , Esporozoítos/inmunología , Transcriptoma , VacunaciónRESUMEN
ChAdOx1 nCoV-19 (AZD1222) is a replication-deficient simian adenovirusâ"vectored vaccine encoding the spike (S) protein of SARS-CoV-2, based on the first published full-length sequence (Wuhan-1). AZD1222 was shown to have 74% vaccine efficacy (VE) against symptomatic disease in clinical trials and over 2.5 billion doses of vaccine have been released for worldwide use. However, SARS-CoV-2 continues to circulate and consequently, variants of concern (VoCs) have been detected, with substitutions in the S protein that are associated with a reduction in virus neutralizing antibody titer. Updating vaccines to include S proteins of VoCs may be beneficial over boosting with vaccines encoding the ancestral S protein, even though current real-world data is suggesting good efficacy against hospitalization and death following boosting with vaccines encoding the ancestral S protein. Using the Syrian hamster model, we evaluated the effect of a single dose of AZD2816, encoding the S protein of the Beta VoC, and efficacy of AZD1222/AZD2816 as a heterologous primary series against challenge with the Beta or Delta variant. We then investigated the efficacy of a single dose of AZD2816 or AZD1222 against the Omicron VoC. As seen previously, minimal to no viral sgRNA could be detected in lungs of vaccinated animals obtained at 5 days post inoculation, in contrast to lungs of control animals. Thus, these vaccination regimens are protective against the Beta, Delta, and Omicron VoCs in the hamster model.
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Accurate and sensitive detection of antibody to SARS-CoV-2 remains an essential component of the pandemic response. Measuring antibody that predicts neutralising activity and the vaccine response is an absolute requirement for laboratory-based confirmatory and reference activity. The viral receptor binding domain (RBD) constitutes the prime target antigen for neutralising antibody. A double antigen binding assay (DABA), providing the most sensitive format has been exploited in a novel hybrid manner employing a solid-phase S1 preferentially presenting RBD, coupled with a labelled RBD conjugate, used in a two-step sequential assay for detection and measurement of antibody to RBD (anti-RBD). This class and species neutral assay showed a specificity of 100 % on 825 pre COVID-19 samples and a potential sensitivity of 99.6 % on 276 recovery samples, predicting quantitatively the presence of neutralising antibody determined by pseudo-type neutralization and by plaque reduction. Anti-RBD is also measurable in ferrets immunised with ChadOx1 nCoV-19 vaccine and in humans immunised with both AstraZeneca and Pfizer vaccines. This assay detects anti-RBD at presentation with illness, demonstrates its elevation with disease severity, its sequel to asymptomatic infection and its persistence after the loss of antibody to the nucleoprotein (anti-NP). It also provides serological confirmation of prior infection and offers a secure measure for seroprevalence and studies of vaccine immunisation in human and animal populations. The hybrid DABA also displays the attributes necessary for the detection and quantification of anti-RBD to be used in clinical practice. An absence of detectable anti-RBD by this assay predicates the need for passive immune prophylaxis in at-risk patients.
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Anticuerpos Antivirales/aislamiento & purificación , COVID-19 , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus/inmunología , Animales , Anticuerpos Neutralizantes/aislamiento & purificación , COVID-19/diagnóstico , ChAdOx1 nCoV-19 , Hurones , Humanos , ARN Viral , Estudios SeroepidemiológicosRESUMEN
Vaccines against SARS-CoV-2 are urgently required, but early development of vaccines against SARS-CoV-1 resulted in enhanced disease after vaccination. Careful assessment of this phenomena is warranted for vaccine development against SARS CoV-2. Here we report detailed immune profiling after ChAdOx1 nCoV-19 (AZD1222) and subsequent high dose challenge in two animal models of SARS-CoV-2 mediated disease. We demonstrate in rhesus macaques the lung pathology caused by SARS-CoV-2 mediated pneumonia is reduced by prior vaccination with ChAdOx1 nCoV-19 which induced neutralising antibody responses after a single intramuscular administration. In a second animal model, ferrets, ChAdOx1 nCoV-19 reduced both virus shedding and lung pathology. Antibody titre were boosted by a second dose. Data from these challenge models on the absence of enhanced disease and the detailed immune profiling, support the continued clinical evaluation of ChAdOx1 nCoV-19.
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Vacunas contra la COVID-19/inmunología , SARS-CoV-2/inmunología , Animales , Anticuerpos Neutralizantes/inmunología , ChAdOx1 nCoV-19 , Hurones , Macaca mulattaRESUMEN
An effective vaccine would be a valuable tool for malaria control and elimination; however, the leading malaria vaccine in development, RTS,S/AS01, provided only partial protection in a Phase 3 trial. R21 is a next-generation RTS,S-like vaccine. We have previously shown in mice that R21 administered in Matrix-M is highly immunogenic, able to elicit complete protection against sporozoite challenge, and can be successfully administered with TRAP based viral-vectors resulting in enhanced protection. In this study, we developed a novel, GMP-compatible purification process for R21, and evaluated the immunogenicity and protective efficacy of ultra-low doses of both R21 and RTS,S when formulated in AS01. We demonstrated that both vaccines are highly immunogenic and also elicit comparable high levels of protection against transgenic parasites in BALB/c mice. By lowering the vaccine dose there was a trend for increased immunogenicity and sterile protection, with the highest dose vaccine groups achieving the lowest efficacy (50% sterile protection). We also evaluated the ability to combine RTS,S/AS01 with TRAP based viral-vectors and observed concurrent induction of immune responses to both antigens with minimal interference when mixing the vaccines prior to administration. These studies suggest that R21 or RTS,S could be combined with viral-vectors for a multi-component vaccination approach and indicate that low dose vaccination should be fully explored in humans to maximize potential efficacy.
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Anticuerpos Antiprotozoarios/sangre , Vacunas contra la Malaria/administración & dosificación , Malaria/prevención & control , Vacunas Sintéticas/administración & dosificación , Animales , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Femenino , Humanos , Inmunización , Malaria/inmunología , Vacunas contra la Malaria/inmunología , Ratones , Ratones Endogámicos BALB C , Ratones Transgénicos , Vacunas Sintéticas/inmunología , Vacunas de Partículas Similares a Virus/administración & dosificación , Vacunas de Partículas Similares a Virus/inmunologíaRESUMEN
Several vaccines have demonstrated efficacy against SARS-CoV-2 mediated disease, yet there is limited data on the immune response induced by heterologous vaccination regimens using alternate vaccine modalities. Here, we present a detailed description of the immune response, in mice, following vaccination with a self-amplifying RNA (saRNA) vaccine and an adenoviral vectored vaccine (ChAdOx1 nCoV-19/AZD1222) against SARS-CoV-2. We demonstrate that antibody responses are higher in two-dose heterologous vaccination regimens than single-dose regimens. Neutralising titres after heterologous prime-boost were at least comparable or higher than the titres measured after homologous prime boost vaccination with viral vectors. Importantly, the cellular immune response after a heterologous regimen is dominated by cytotoxic T cells and Th1+ CD4 T cells, which is superior to the response induced in homologous vaccination regimens in mice. These results underpin the need for clinical trials to investigate the immunogenicity of heterologous regimens with alternate vaccine technologies.
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Vacunas contra la COVID-19/administración & dosificación , COVID-19/prevención & control , ARN Viral/administración & dosificación , SARS-CoV-2/inmunología , Vacunación/métodos , Animales , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/inmunología , Vacunas contra la COVID-19/genética , Vacunas contra la COVID-19/inmunología , ChAdOx1 nCoV-19 , Inmunización Secundaria , Inmunogenicidad Vacunal , Ratones , ARN Viral/genética , ARN Viral/inmunología , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/inmunología , Linfocitos T Citotóxicos/inmunología , Células TH1/inmunología , Vacunas Sintéticas/administración & dosificación , Vacunas Sintéticas/genética , Vacunas Sintéticas/inmunologíaRESUMEN
Salmonella is contracted through the consumption of untreated water and contaminated food. The contraction and spread of water-related Salmonella in resource-poor communities can be reduced by using solar disinfection (SODIS) to treat the water before its consumption. SODIS is a water sanitizing technique that relies on natural sunshine. It is a cost-effective, inexpensive, environmentally, and user-friendly means of treating microbiologically contaminated water. This water disinfection method has saved many lives in communities vulnerable to water-related infections worldwide. At present, the success of SODIS has mainly been attributed to permanent inactivation of water pathogens ability to grow. However, little to no information exists as to whether immune responses to the solar inactivated pathogens are induced in SODIS water consumers. This study assessed the potential for solar inactivated S. Typhimurium to induce an immune response in mice. Results show that solar inactivated S. Typhimurium can induce bactericidal antibodies against S. Typhimurium. Furthermore, an increase in the secretion of interferon-gamma (IFN-γ) was observed in mice given the solar inactivated S. Typhimurium. These findings suggest that solar inactivated S. Typhimurium induces a humoral and cellular immune response. However, the level of protection afforded by these responses requires further investigation.