Editing HIV vaccine development (section)

===Animal model===
[[File:2006-12-09 Chipanzees D Bruyere.JPG|thumb| Young chimpanzees from [[Tchimpounga Sanctuary]] ([[Republic of the Congo]])]]
The typical [[animal model]] for vaccine research is the monkey, often the [[macaque]]. Monkeys can be infected with [[Simian immunodeficiency virus|SIV]] or the chimeric SHIV for research purposes. However, the well-proven route of trying to induce neutralizing antibodies by vaccination has stalled because of the great difficulty in stimulating antibodies that neutralise heterologous primary HIV isolates.<ref>{{cite journal | vauthors = Poignard P, Sabbe R, Picchio GR, Wang M, Gulizia RJ, Katinger H, Parren PW, Mosier DE, Burton DR | display-authors = 6 | title = Neutralizing antibodies have limited effects on the control of established HIV-1 infection in vivo | journal = Immunity | volume = 10 | issue = 4 | pages = 431–8 | date = April 1999 | pmid = 10229186 | doi = 10.1016/S1074-7613(00)80043-6 | doi-access = free }}</ref> Some vaccines based on the virus envelope have protected chimpanzees or macaques from homologous virus challenge,<ref>{{cite journal | vauthors = Berman PW, Gregory TJ, Riddle L, Nakamura GR, Champe MA, Porter JP, Wurm FM, Hershberg RD, Cobb EK, Eichberg JW | display-authors = 6 | title = Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160 | journal = Nature | volume = 345 | issue = 6276 | pages = 622–5 | date = June 1990 | pmid = 2190095 | doi = 10.1038/345622a0 | bibcode = 1990Natur.345..622B | s2cid = 4258128 | doi-access = free }}</ref> but in clinical trials, humans who were immunised with similar constructs became infected after later exposure to HIV-1.<ref>{{cite journal | vauthors = Connor RI, Korber BT, Graham BS, Hahn BH, Ho DD, Walker BD, Neumann AU, Vermund SH, Mestecky J, Jackson S, Fenamore E, Cao Y, Gao F, Kalams S, Kunstman KJ, McDonald D, McWilliams N, Trkola A, Moore JP, Wolinsky SM | display-authors = 6 | title = Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines | journal = Journal of Virology | volume = 72 | issue = 2 | pages = 1552–76 | date = February 1998 | pmid = 9445059 | pmc = 124637 | doi =  10.1128/JVI.72.2.1552-1576.1998}}</ref>

There are some differences between SIV and HIV that may introduce challenges in the use of an animal model. The animal model can be extremely useful but at times controversial.<ref>{{cite journal | vauthors = Morgan C, Marthas M, Miller C, Duerr A, Cheng-Mayer C, Desrosiers R, Flores J, Haigwood N, Hu SL, Johnson RP, Lifson J, Montefiori D, Moore J, Robert-Guroff M, Robinson H, Self S, Corey L | display-authors = 6 | title = The use of nonhuman primate models in HIV vaccine development | journal = PLOS Medicine | volume = 5 | issue = 8 | pages = e173 | date = August 2008 | pmid = 18700814 | pmc = 2504486 | doi = 10.1371/journal.pmed.0050173 | author-link8 = Nancy Haigwood | doi-access = free }}</ref>

There is a new animal model strongly resembling that of HIV in humans. Generalized immune activation as a direct result of activated CD4+ T cell killing - performed in mice allows new ways of testing HIV behaviour.<ref>{{cite journal | vauthors = Marques R, Williams A, Eksmond U, Wullaert A, Killeen N, Pasparakis M, Kioussis D, Kassiotis G | display-authors = 6 | title = Generalized immune activation as a direct result of activated CD4+ T cell killing | journal = Journal of Biology | volume = 8 | issue = 10 | page = 93 | year = 2009 | pmid = 19943952 | pmc = 2790834 | doi = 10.1186/jbiol194 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Vrisekoop N, Mandl JN, Germain RN | title = Life and death as a T lymphocyte: from immune protection to HIV pathogenesis | journal = Journal of Biology | volume = 8 | issue = 10 | page = 91 | year = 2009 | pmid = 19951397 | pmc = 2790836 | doi = 10.1186/jbiol198 | doi-access = free }}</ref>

[[National Institute of Allergy and Infectious Diseases|NIAID]]-funded SIV research has shown that challenging monkeys with a [[cytomegalovirus]] (CMV)-based SIV vaccine results in containment of virus. Typically, virus replication and dissemination occurs within days after infection, whereas vaccine-induced T cell activation and recruitment to sites of viral replication take weeks. Researchers hypothesized that vaccines designed to maintain activated effector memory T cells might impair viral replication at its earliest stage.{{Citation needed|date=October 2012}}

Specific vaccines may also need specialized animal models. For example, vaccines designed to produce VRC01-type antibodies require human-like V<sub>H</sub> alleles to be present. For organisms like mice, the human allele must be inserted into their genome to produce a useful mimic.<ref>{{cite journal |last1=Lin |first1=YR |last2=Parks |first2=KR |last3=Weidle |first3=C |last4=Naidu |first4=AS |last5=Khechaduri |first5=A |last6=Riker |first6=AO |last7=Takushi |first7=B |last8=Chun |first8=JH |last9=Borst |first9=AJ |last10=Veesler |first10=D |last11=Stuart |first11=A |last12=Agrawal |first12=P |last13=Gray |first13=M |last14=Pancera |first14=M |last15=Huang |first15=PS |last16=Stamatatos |first16=L |title=HIV-1 VRC01 Germline-Targeting Immunogens Select Distinct Epitope-Specific B Cell Receptors. |journal=Immunity |date=13 October 2020 |volume=53 |issue=4 |pages=840–851.e6 |doi=10.1016/j.immuni.2020.09.007 |pmid=33053332|pmc=7735217 |doi-access=free }}</ref> Murines are also experimental animals in AIDS and also murine AIDS and human AIDS are similar. Immunological analysis and genetic studies reveal resistant gene(s) in the H-2 complex of mice, an indication that genetic differences in mice could modify features of HIV disease. The defective murine leukemia virus is the major etiologic agent of MAIDS, which seems to be able to induce disease in the absence of virus replication. Target cell proliferation and oligoclonal expansion are induced by the virus, which suggests repressed immunity seen in mice thus referred to as paraneoplastic syndrome. This is further supported by the good response(s) of MAIDS mice to antineoplastic agents. This animal model is useful in demonstrating the emergence of novel hypotheses about AIDS, including the roles of defective HIV and HIV replication in the progression of the disease, and also the importance of identifying the HIV targeted cells ''in vivo.''<ref>{{Cite book |last1=Ibeh |first1=Bartholomew Okechukwu |url= |title=Experimental Animal Models of HIV/AIDS for Vaccine Trials |last2=Ashano |first2=Efejiro |date=2018-11-05 |publisher=IntechOpen |isbn=978-1-78923-165-6 |language=en }}</ref>