**Author details**

living system [80]. As discussed earlier, a standardized animal model that provides all the information required for advancing a new vaccine through the preclinical stage has still not been met and even if it were, it is still bereft with problems bordering on bioethics. Current trend suggests that humanized mice (**Table 3**) more accurately predict vaccine outcomes that

172 Experimental Animal Models of Human Diseases - An Effective Therapeutic Strategy

**5. HIV preclinical vaccine trials and predictive biomarker discovery** 

introduced engineered HSCs that expresses an HIV-specific T cell receptor (TCR).

It is possible to design an integrated preclinical approach using PDX models organized with systems biology to enable the discovery and development of predictive biomarkers in order to classify clinical tumor responsiveness to a novel agent [82]. Peradventure the classifier achieved a high level of accuracy in the experiment, and biomarker-driven clinical trials could be developed based on the prevalent rate of the identified biomarkers and their link with efficacy.

The actual mechanism of sexual transmission is not precisely defined. What is known, however, is that HIV must be transmitted via the mucosal surfaces of the genital tract in both heteroand homosexual cases [83]. The fact that some individuals remain uninfected despite multiple exposures, whereas others get infected after an exposure to HIV-infected semen further confounds the situation. An animal model adapted to mucosal transmission of the virus would aid elucidation of the mechanisms and dose of virus required for transmission and provide a system for testing pharmacologic and biologic cofactors that may affect HIV transmission.

Although intravenous inoculation of SIV into macaques is a near perfect model for studies of pathogenesis, this route is not appropriate for studying factors involved in the sexual transmission

To accelerate effort in bridging the translational gap between preclinical evaluation and clinical trials, it is pertinent to make animal model testing more clinical trial like. It is important that clinical endpoints may not be easily established in animal models because of the use of questionnaires to derive the quality of life issues from end users and cannot be replicated in experimental animals; however, there are recent attempts to model pain questionnaires in animals [81]. Obviously, animal models could be designed to use other endpoints that relate or translate into the expected endpoints of clinical trials. The humanized NSG among all other models have been successfully used for multiple *in vivo* preclinical validation studies. Potentially tested areas of validation include: (1) activation of human NK cells with an IL-15 superagonist to inhibit acute HIV infection; (2) delivering anti-CCR5 and antiviral silencing RNAs (siRNA) direct delivery to T cells in order to control viral replication and prevent CD4+ T cell loss; (3) provision of prophylactic protection from HIV infection through induction of neutralizing anti-HIV monoclonal antibodies and (4) suppression of viral replication through

approximate humans.

**in animal models**

**6. Next generation models**

Bartholomew Okechukwu Ibeh1 \* and Efejiro Ashano<sup>2</sup>

\*Address all correspondence to: barthokeyibeh@yahoo.com

1 Laboratory of Animal Models for Human Diseases, Medical Biotechnology Department, National Biotechnology Development Agency, Abuja, Nigeria

2 Immunovirology and Vaccine Development Laboratory (IVL), Medical Biotechnology Department, National Biotechnology Development Agency, Abuja, Nigeria
