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Rift Valley fever virus (RVFV) is a mosquito-borne zoonotic pathogen that causes periodic outbreaks of abortion in ruminant species and hemorrhagic disease in humans in sub-Saharan Africa. These outbreaks have a significant impact on veterinary and public health. Its introduction to the Arabian Peninsula in 2003 raised concerns of further spread of this transboundary pathogen to non-endemic areas. These concerns are supported by the presence of competent vectors in many non-endemic countries. There is no licensed RVF vaccine available for humans and only a conditionally licensed veterinary vaccine available in the United States. Currently employed modified live attenuated virus vaccines in endemic countries lack the ability for differentiating infected from vaccinated animals (DIVA). Previously, the efficacy of a recombinant subunit vaccine based on the RVFV Gn and Gc glycoproteins, derived from the 1977 human RVFV isolate ZH548, was demonstrated in sheep. In the current study, cattle were vaccinated subcutaneously with the Gn only, or Gn and Gc combined, with either one or two doses of the vaccine and then subjected to heterologous virus challenge with the virulent Kenya-128B-15 RVFV strain, isolated from Aedes mosquitoes in 2006. The elicited immune responses by some vaccine formulations (one or two vaccinations) conferred complete protection from RVF within 35 days after the first vaccination. Vaccines given 35 days prior to RVFV challenge prevented viremia, fever and RVFV-associated histopathological lesions. This study indicates that a recombinant RVFV glycoprotein-based subunit vaccine platform is able to prevent and control RVFV infections in target animals.

Epizootic hemorrhagic disease virus (EHDV) is an arthropod-transmitted RNA virus and the causative agent of epizootic hemorrhagic disease (EHD) in wild and domestic ruminants. In North America, white-tailed deer (WTD) experience the highest EHD-related morbidity and mortality, although clinical disease is reported in cattle during severe epizootics. No commercially licensed EHDV vaccine is available in North America. The objective of this study was to develop and evaluate a subunit vaccine candidate to control EHD in WTD. Recombinant VP2 (rVP2) outer capsid proteins of EHDV serotypes 2 (EHDV-2) and 6 (EHDV-6) were produced in a baculovirus-expression system. Mice and cattle vaccinated with EHDV-2 or EHDV-6 rVP2 produced homologous virus-neutralizing antibodies. In an immunogenicity/efficacy study, captive-bred WTD received 2 doses of EHDV-2 rVP2 or sham vaccine, then were challenged with wild-type EHDV-2 at 30 d post vaccination. None of the rVP2-vaccinated deer developed clinical disease, no viral RNA was detected in their blood or tissues (liver, lung, spleen, kidney), and no EHDV-induced lesions were observed. Sham-vaccinated deer developed clinical disease with viremia and typical EHD vascular lesions. Here, we demonstrate a rVP2 subunit vaccine that can provide protective immunity from EHDV infection and which may serve as an effective tool in preventing clinical EHD and reducing virus transmission.

African swine fever virus (ASFV) causes high morbidity and mortality in swine (Sus scrofa), for which there is no commercially available vaccine. Recent outbreaks of the virus in Trans-Caucasus countries, Eastern Europe, Belgium and China highlight the urgent need to develop effective vaccines against ASFV. Previously, we evaluated the immunogenicity of a vaccination strategy designed to test various combinations of ASFV antigens encoded by DNA plasmids and recombinant proteins with the aim to activate both humoral and cellular immunity. Based on our previous results, the objective of this study was to test the combined DNA-protein vaccine strategy using a cocktail of the most immunogenic antigens against virulent ASFV challenge. Pigs were vaccinated three times with a cocktail that included ASFV plasmid DNA (CD2v, p72, p32, +/−p17) and recombinant proteins (p15, p35, p54, +/−p17). Three weeks after the third immunization, all pigs were challenged with the virulent ASFV Armenia 2007 strain. The results showed that vaccinated pigs were not protected from ASFV infection or disease. Compared to the non-vaccinated controls, earlier onset of clinical signs, viremia, and death were observed for the vaccinated animals following virulent ASFV challenge. ASFV induced pathology was also enhanced in the vaccinated pigs. Furthermore, while the vaccinated pigs developed antigen-specific antibodies, immunized pig sera at the time of challenge lacked the capacity to neutralize virus, and instead was observed to enhance ASFV infection in vitro. The results of this work points to a putative immune enhancement mechanism involved in ASFV pathogenesis that warrants further investigation. This pilot study provides insight for the selection of appropriate combinations of ASFV antigens for the development of a rationally-designed, safe, and efficacious vaccine for ASF., This work was funded by grants from the U.S. Department of Homeland Security under Grant Award Number DHS-2010-ST-061-AG0001 for the Center of Excellence for Emerging and Zoonotic Animal Disease (CEEZAD) and the State of Kansas National Bio and Agro-Defense Facility (NBAF) transition fund, We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI)

The antigenically conserved hemagglutinin stalk region is a target for universal influenza virus vaccines since antibodies against it can provide broad protection against influenza viruses of different subtypes. We tested a universal influenza virus vaccination regimen based on sequential immunization with chimeric hemagglutinin (HA) containing viruses in a swine influenza virus pig model with maternal antibodies against pandemic H1N1. Vaccines were administered as live attenuated virus or inactivated influenza virus split vaccine (+/− Emulsigen adjuvant). As controls, we included groups that received trivalent inactivated influenza vaccine that contained pandemic H1N1 antigens, inactivated adjuvanted H1N2 vaccine (control group for vaccine associated enhanced respiratory disease in the pig model) or mock-vaccination. No induction of H1 head or stalk-specific antibody responses was observed upon vaccination, while responses against H3 and influenza B HA were elicited in the group vaccinated with the trivalent vaccine. Four weeks post vaccination, pigs were intratracheally challenged with pandemic H1N1 virus and euthanized 5 days after challenge. Despite the lack of detectable anti-stalk immunity, the chimeric hemagglutinin vaccine resulted in better clinical outcomes compared to control groups.

The antigenically conserved hemagglutinin stalk region is a target for universal influenza virus vaccines since antibodies against it can provide broad protection against influenza viruses of different subtypes. We tested a universal influenza virus vaccination regimen based on sequential immunization with chimeric hemagglutinin (HA) containing viruses in a swine influenza virus pig model with maternal antibodies against pandemic H1N1. Vaccines were administered as live attenuated virus or inactivated influenza virus split vaccine (+/&minus, Emulsigen adjuvant). As controls, we included groups that received trivalent inactivated influenza vaccine that contained pandemic H1N1 antigens, inactivated adjuvanted H1N2 vaccine (control group for vaccine associated enhanced respiratory disease in the pig model) or mock-vaccination. No induction of H1 head or stalk-specific antibody responses was observed upon vaccination, while responses against H3 and influenza B HA were elicited in the group vaccinated with the trivalent vaccine. Four weeks post vaccination, pigs were intratracheally challenged with pandemic H1N1 virus and euthanized 5 days after challenge. Despite the lack of detectable anti-stalk immunity, the chimeric hemagglutinin vaccine resulted in better clinical outcomes compared to control groups.