Poliomyelitis has nearly been eradicated through the efforts of the World Health Organization’s Global Eradication Initiative raising questions on containment of the virus after it has been eliminated in the wild. Most manufacture of inactivated polio vaccines currently requires the growth of large amounts of highly virulent poliovirus, and release from a production facility after eradication could be disastrous; WHO have therefore recommended the use of the attenuated Sabin strains for production as a safer option although it is recognised that they can revert to a transmissible paralytic form. We have exploited the understanding of the molecular virology of the Sabin vaccine strains to design viruses that are extremely genetically stable and hyperattenuated. The viruses are based on the type 3 Sabin vaccine strain and have been genetically modified in domain V of the 5’ non-coding region by changing base pairs to produce a cassette into which capsid regions of other serotypes have been introduced. The viruses give satisfactory yields of antigenically and immunogenically correct viruses in culture, are without measurable neurovirulence and fail to infect non-human primates under conditions where the Sabin strains will do so.

South American Zika virus (ZIKV) recently emerged as a novel human pathogen, linked with neurological disorders. However, comparative ZIKV infectivity studies in New World primates are lacking. Two members of the Callitrichidae family, common marmosets (Callithrix jacchus) and red-bellied tamarins (Saguinus labiatus), were highly susceptible to sub-cutaneous challenge with the Puerto Rico-origin ZIKVPRVABC59 strain. Both exhibited rapid, high, acute viraemia with early neuroinvasion (3 days) in peripheral and central nervous tissue. ZIKV RNA levels in blood and tissues were significantly higher in New World hosts compared to Old World species (Macaca mulatta, Macaca fascicularis). Tamarins and rhesus macaques exhibited loss of zonal occludens-1 (ZO-1) staining, indicative of a compromised blood-brain barrier 3 days post-ZIKV exposure. Early, widespread dissemination across multiple anatomical sites distant to the inoculation site preceded extensive ZIKV persistence after 100 days in New and Old World lineages, especially lymphoid, neurological and reproductive sites. Prolonged persistence in brain tissue has implications for otherwise resolved human ZIKV infection. High susceptibility of distinct New World species underscores possible establishment of ZIKV sylvatic cycles in primates indigenous to ZIKV endemic regions. Tamarins and marmosets represent viable New World models for ZIKV pathogenesis and therapeutic intervention studies, including vaccines, with contemporary strains.

Optimum strategies to elicit and maintain antibodies at mucosal portals of virus entry are critical for the development of vaccines against human immunodeficiency virus (HIV). Here we show in non-human primates that a novel regimen of repeated intravaginal delivery of a non-adjuvanted, soluble recombinant trimeric HIV-1CN54 clade C envelope glycoprotein (gp140) administered in Carbopol gel can prime for B-cell responses even in the absence of seroconversion. Following 3 cycles of repeated intravaginal administration, throughout each intermenses interval, 3 of 4 macaques produced or boosted systemic and mucosally-detected antibodies upon intramuscular immunisation with gp140 formulated in AS01 adjuvant. Reciprocally, a single intramuscular immunisation primed 3 of 4 macaques for antibody boosting after a single cycle of intravaginal immunisation. Virus neutralising activity was detected against clade C and clade B HIV-1 envelopes but was restricted to highly neutralisation sensitive pseudoviruses.

Zika virus (ZIKV) causes neurological complications in susceptible individuals, highlighted in the recent South American epidemic. Natural ZIKV infection elicits host responses capable of preventing subsequent re-infection, raising expectations for effective vaccination. Defining protective immune correlates will inform viral intervention strategies, particularly vaccine development. Non-human primate (NHP) species are susceptible to ZIKV and represent models for vaccine development. The protective efficacy of a human anti-ZIKV convalescent plasma pool (16/320-14) developed as a candidate reference material for a WHO International Standard was evaluated in macaques. Convalescent plasma administered to four cynomolgus macaques (Macaca fascicularis) intra-peritoneally 24 hrs prior to sub-cutaneous challenge with 103 pfu ZIKVPRVABC59 protected against detectable infection, with absence of detectable ZIKV RNA in blood and lymphoid tissues. Passively immunised anti-ZIKV immunoglobulin administered prior to time of challenge remained present only at very low levels 42 days post-challenge. Absence of de novo antibody responses in passively immunised macaques indicate sterilising immunity compared with naïve challenge controls that exhibited active ZIKV-specific IgM and IgG responses post-challenge. Demonstration that the presence of convalescent anti-ZIKV at levels of 400 IU/mL neutralising antibody protects against virus challenge provides a scientific framework for development of anti-ZIKV vaccines and facilitates regulatory approval.

The detailed study of immune effector mechanisms in primate models of infectious disease has been limited by the inability to adoptively transfer lymphocytes from vaccinated animals into naïve immunocompetent recipients. Recent advances in our understanding of the Major Histocompatibility Complex diversity of Mauritian cynomolgus macaques enabled the establishment of a breeding program to generate Major Histocompatibility Complex (MHC)-identical animals. The current study utilised this resource to achieve an improved model of adoptive transfer of lymphocytes in macaques. The effect of route of transfusion on persistence kinetics of adoptively transferred lymphocytes was evaluated in an autologous transfer system. Results indicated that peripheral persistence kinetics were comparable following infusion by different routes, and that cells were detectable at equivalent levels in lymphoid tissues six weeks post-infusion. In a pilot-scale experiment, the persistence of adoptively transferred lymphocytes was compared in MHC-identical siblings and MHC-identical unrelated recipients. Lymphocytes transferred intra-peritoneally were detectable in the periphery within one hour of transfer and circulated at detectable levels in the periphery and lymph nodes for 10 days. Donor lymphocytes were detectable at higher levels in MHC-identical siblings compared with unrelated animals, however the total time of persistence did not differ. These results demonstrate a further refinement of the lymphocyte adoptive transfer system in Mauritian cynomolgus macaques and provide a foundation for hitherto impractical experiments to investigate mechanisms of cellular immunity in primate models of infectious disease.