Elicitation of Protective Antibodies against a Broad Panel of H1N1 Viruses in Ferrets Preimmune to Historical H1N1 Influenza Viruses

ABSTRACT Most preclinical animal studies test influenza vaccines in immunologically naive animal models, even though the results of vaccination may not accurately reflect the effectiveness of vaccine candidates in humans that have preexisting immunity to influenza. In this study, novel, broadly reactive influenza vaccine candidates were assessed in preimmune ferrets. These animals were infected with different H1N1 isolates before being vaccinated or infected with another influenza virus. Previously, our group has described the design and characterization of computationally optimized broadly reactive hemagglutinin (HA) antigens (COBRA) for H1N1 isolates. Vaccinating ferrets with virus-like particle (VLP) vaccines expressing COBRA HA proteins elicited antibodies with hemagglutination inhibition (HAI) activity against more H1N1 viruses in the panel than VLP vaccines expressing wild-type HA proteins. Specifically, ferrets infected with the 1986 virus and vaccinated with a single dose of the COBRA HA VLP vaccines elicited antibodies with HAI activity against 11 to 14 of the 15 H1N1 viruses isolated between 1934 and 2013. A subset of ferrets was infected with influenza viruses expressing the COBRA HA antigens. These COBRA preimmune ferrets had superior breadth of HAI activity after vaccination with COBRA HA VLP vaccines than COBRA preimmune ferrets vaccinated with VLP vaccines expressing wild-type HA proteins. Overall, priming naive ferrets with COBRA HA based viruses or using COBRA HA based vaccines to boost preexisting antibodies induced by wild-type H1N1 viruses, COBRA HA antigens elicited sera with the broadest HAI reactivity against multiple antigenic H1N1 viral variants. This is the first report demonstrating the effectiveness of a broadly reactive or universal influenza vaccine in a preimmune ferret model. IMPORTANCE Currently, many groups are testing influenza vaccine candidates to meet the challenge of developing a vaccine that elicits broadly reactive and long-lasting protective immune responses. The goal of these vaccines is to stimulate immune responses that react against most, if not all, circulating influenza strains, over a long period of time in all populations of people. Commonly, these experimental vaccines are tested in naive animal models that do not have anti-influenza immune responses; however, humans have preexisting immunity to influenza viral antigens, particularly antibodies to the HA and NA glycoproteins. Therefore, this study investigated how preexisting antibodies to historical influenza viruses influenced HAI-specific antibodies and protective efficacy using a broadly protective vaccine candidate.

The effect of demonstrator reward on social learning of operant key pecking by domestic hens

Social learning is said to occur when social interaction facilitates the acquisition of a novel pattern of behaviour. It usually takes the form of an experienced animal (the demonstrator) performing a behaviour such that a naive animal (the observer) subsequently expresses the same novel behaviour, earlier or more completely than it would have done using individual learning. Social learning is involved in the transmission of a great variety of behaviours, e.g. tool-use, food preferences, and has also been implicated in maladaptive behaviours such as stereotypies in voles. In studies of social learning, the observers usually see the demonstrators receive a reward for performing the required behaviour. But, the role of the reward has rarely been investigated and results have been equivocal. Understanding the role of demonstrator reward on social learning is necessary to assess the cognitive abilities of individuals of different species, and aids understanding of the transmission of maladaptive behaviours.

Is imprinting such a special case?

As the result of relatively brief exposure to a particular type of object early in life, many birds and mammals will form strong and exclusive attachments to that object. This is known as ‘filial imprinting’. Early experience can also have long-lasting effects on sexual preferences, but the conditions are different from those in which the first attachments are formed. Some of the characteristics of imprinting are undoubtedly because of the naive animal searching for and responding selectively to particular stimuli. But that is not all. At least two types of plastic change seem to be involved: establishing an internal representation of the familiar object and pre-emptive capturing by that representation of the systems controlling filial behaviour and, much later in development, sexual behaviour. The second plastic change is likely to generate the phenomenon of a sensitive period and gives the formation of social attachments some of its other peculiar properties. The first change is likely to be the process used in most forms of recognition. Distinguishing between the sub-processes that underlie an overall change in behaviour serves to make some overdue links between different areas of knowledge about learning which have hitherto been poorly connected.

Global Stereopsis in Rhesus Monkeys

In three separate experiments an attempt was made to demonstrate global stereopsis in two rhesus monkeys by using random dot stereograms projected and viewed through polarizing filters. Although both animals learned a number of discriminations, control tests showed that both were perceiving non-depth cues such as monocular identification of minute pattern differences or brightness differences caused by reflections of polarized light. In a final experiment red/green anaglyph forms of the stereograms were viewed through red/green filters. Both monkeys, together with a third experimentally naive animal, showed incontrovertible evidence of prompt discrimination based on stereopsis. This paper makes a number of recommendations about the use of random dot stereograms to demonstrate global stereopsis in animals.