Morphological and physiological features in small ruminants: an adaptation strategy for survival under changing climatic conditions.

Climate change due to natural human activity is a significant global phenomenon affecting the sustainability of most countries' livestock industries. Climate change factors such as ambient temperature, relative humidity, direct and indirect sun radiation, and wind have significant consequences on feed, water, pasture availability, and the re-emergence of diseases in livestock. All these variables have a considerable impact on livestock production and welfare. However, animals' ability to respond and adapt to changes in climate differs within species and breeds. Comparatively, small ruminants are more adaptive to the adverse effects of climate change than large ruminants in terms of reproduction performance, survival, production yield, and resistance to re-emerging diseases. This is mainly due to their morphological features against harsh climate effects. Tropical breeds are more adaptive to the adverse effects of climate change than small temperate ruminants. However, the difference in morphological characteristics towards adaptation to the impact of climate change will guide the development of suitable policies on the selection of breeding stock suitable for different regions in the world. The choice of breeds based on morphological features and traits is an essential strategy in mitigating and minimizing the effects of climate change on small ruminants' production and welfare. This review highlights the adaptive morphological features within and among breeds of small ruminants toward adaptation to climate change.

Recent advances in experimental polyphosphazene adjuvants and their mechanisms of action.

Vaccination continues to be a very important public health intervention to control infectious diseases in the world. Subunit vaccines are generally poorly immunogenic and require the addition of adjuvants to induce protective immune responses. Despite their critical role in vaccines, adjuvant mechanism of action remains poorly understood, which is a barrier to the development of new, safe and effective vaccines. In the present review, we focus on recent progress in understanding the mechanisms of action of the experimental adjuvants poly[di(carboxylatophenoxy)phosphazene] (PCPP) and poly[di(sodiumcarboxylatoethyl-phenoxy)phosphazene] (PCEP) (in this review, adjuvants PCPP and PCEP are collectively referred to as PZ denoting polyphosphazenes). PZs are high molecular weight, water-soluble, synthetic polymers that have been shown to regulate innate immune response genes, induce cytokines and chemokines secretion at the site of injection and, also, induce immune cell recruitment to the site of injection to create a local immune-competent environment. There is an evidence that as well as its role as an immunoadjuvant (that activate innate immune responses), PZ can also act as a vaccine carrier. The mechanism of action that explains how PZ leads to these effects is not known and is a barrier to the development of designer vaccines.

Polyphosphazenes as Adjuvants for Animal Vaccines and Other Medical Applications.

Polyphosphazenes are a class of experimental adjuvants that have shown great versatility as vaccine adjuvants in many animal species ranging from laboratory rodents to large animal species. Their adjuvant activity has shown promising results with numerous viral and bacterial antigens, as well as with crude and purified antigens. Vaccines adjuvanted with polyphosphazenes can be delivered via systemic and mucosal administration including respiratory, oral, rectal, and intravaginal routes. Polyphosphazenes can be used in combination with other adjuvants, further enhancing immune responses to antigens. The mechanisms of action of polyphosphazenes have not fully been defined, but several systematic studies have suggested that they act primarily by activating innate immunity. In the present review, we will highlight progress in the development of polyphosphazenes as adjuvants in animals and their other medical applications.

Experimental PCEP-Adjuvanted Swine Influenza H1N1 Vaccine Induced Strong Immune Responses but Did Not Protect Piglets against Heterologous H3N2 Virus Challenge.

Vaccination is the most efficient method of protection against influenza infections. However, the rapidly mutating viruses and development of new strains make it necessary to develop new influenza vaccines annually. Hence, vaccines that stimulate cross-protection against multiple influenza subtypes are highly sought. Recent evidence suggests that adjuvants such as PCEP that promote Th1-type T cell and Th2-type T cell immune responses and broad-spectrum immune responses may confer cross-protection against heterologous influenza strains. In this study, we evaluated whether the immunogenic and protective potential of PCEP-adjuvanted inactivated swine influenza virus H1N1 vaccine can protect pigs immunized against live H3N2 virus. Piglets were vaccinated via the intradermal route with PCEP-adjuvanted inactivated swine influenza virus (SIV) H1N1 vaccine, boosted at day 21 with the same vaccines then challenged with infectious SIV H3N2 virus at day 35 via the tracheobronchial route. The pigs showed significant anti-H1N1 SIV specific antibody titres and H1N1 SIV neutralizing antibody titres, and these serum titres remained after the challenge with the H3N2 virus. In contrast, vaccination with anti-H1N1 SIV did not trigger anti-H3N2 SIV antibody titres or neutralizing antibody titres and these titres remained low until pigs were challenged with H3N2 SIV. At necropsy (six days after challenge), we collected prescapular lymph nodes and tracheobronchial draining the vaccination sites and challenge site, respectively. ELISPOTs from lymph node cells restimulated ex vivo with inactivated SIV H1N1 showed significant production of IFN-γ in the tracheobronchial cells, but not the prescapular lymph nodes. In contrast, lymph node cells restimulated ex vivo with inactivated SIV H1N1 showed significantly higher IL-13 and IL-17A in the prescapular lymph nodes draining the vaccination sites relative to unchallenged animals. Lung lesion scores show that intradermal vaccination with H1N1 SIV plus PCEP did not prevent lesions when the animals were challenged with H3N2. These results confirm previous findings that PCEP is effective as a vaccine adjuvant in that it induces strong immune responses and protects against homologous swine influenza H1N1 virus, but the experimental H1N1 vaccine failed to cross-protect against heterologous H3N2 virus.

Innate immune response profiles in pigs injected with vaccine adjuvants polydi(sodium carboxylatoethylphenoxy)phosphazene (PCEP) and Emulsigen.

Vaccines are formulated with adjuvants to enhance or direct antigen-specific immune responses against pathogens. However, the mechanisms of action (MOA) of adjuvants are not well understood and are under-investigated in large animal species. We have previously reported that injection of mice induced innate immune responses as indicated by increased cell recruitment and cytokine production at the site of injection with polyphosphazene (PCEP) adjuvant. In the present study, we evaluated whether PCEP induced similar innate immune responses in pigs. Piglets were injected with either PCEP or Emulsigen intradermally (I.D.) and the local cellular infiltration and cytokine production were evaluated at the site of injection and the draining lymph nodes. PCEP induced infiltration of macrophages, T and B cells, leucocytes and necrotic debris at the site of injection as well as PCEP-induced leucocyte infiltration in the draining lymph nodes. Emulsigen induced diffuse infiltration of leucocytes, macrophages, and lymphocytes at the site of injection as well as at the draining lymph nodes. PCEP induced significant production of interleukin IL-1ß, and IL-13 at the site of injection and IL-1ß, and IL-6 at the draining lymph nodes. Emulsigen promoted the production of IL-1ß, IL-6, and IL-12 at the site of injection but not in the draining lymph nodes. No cytokines were detected in blood after injection of either adjuvant. Together, our data indicate that in pigs, the adjuvants PCEP and Emulsigen stimulate early innate immune responses at the injection site by creating an immunocompetent environment that may contribute to increased immunogenicity of the co-administered antigens.

Intradermal immunization with inactivated swine influenza virus and adjuvant polydi(sodium carboxylatoethylphenoxy)phosphazene (PCEP) induced humoral and cell-mediated immunity and reduced lung viral titres in pigs.

Swine influenza virus is endemic worldwide and it is responsible for significant economic losses to the swine industry. A vaccine that stimulates a rapid and long-lasting protective immune response to prevent this infection is highly sought. Poly[di(sodium carboxylatoethylphenoxy)-phosphazene (PCEP) has demonstrated adjuvant activity when formulated as part of multiple vaccines in mice and pigs. In this study we examined the magnitude and type of immune response induced in pigs vaccinated via the intramuscular or intradermal routes with inactivated swine influenza virus (SIV) H1N1 vaccine formulated with PCEP. Intradermal administration of PCEP-adjuvanted inactivated SIV vaccine stimulated significant anti-SIV antibody titres, increased neutralizing antibodies, and significantly reduced lung virus load with limited reduction of gross lung lesions after challenge with virulent H1N1 relative to control animals. These results indicate that PCEP may be effective as a vaccine adjuvant against swine influenza viruses in pigs and should be considered a potential candidate adjuvant for future swine intradermal influenza vaccines.