CD4 ⁺ T cells play a major role in protective immunity against the blood stage of malaria, but the mechanism of protection is unclear. By adoptive transfer of cloned T cell lines, direct evidence is provided that both T _H 1 and T _H 2 subsets of CD4 ⁺ T cells can protect mice against Plasmodium chabaudi chabaudi infection. T _H 1 cells protect by a nitric oxide-dependent mechanism, whereas T _H 2 cells protect by the enhancement and accelerated production of specific immunoglobulin G1 antibody.

Objective: To use our knowledge of the three-dimensional structure and self-assembly mechanism of RNA bacteriophage capsids to develop novel virus-like particles (VLPs) for drug delivery and epitope presentation. Methods: Site-directed mutagenesis of a recombinant MS2 coat protein expression construct has been used to generate translational fusions encompassing short epitope sequences. These chimeric proteins still self-assemble in vivo into T = 3 shells with the foreign epitope in an accessible location. Covalent conjugation has also been used to generate RNA stem-loops attached to the toxin, ricin A chain, or to nucleotide-based drugs, that are still capable of stimulating self-assembly of the capsid in vitro. These packaged drugs can then be directed to specific cells in culture by further covalent decoration of the capsids with targeting molecules. Results: Chimeric VLPs are strongly immunogenic when carrying either B or T cell epitopes, the latter generating cytokine profiles consistent with memory responses. Immune responses to the underlying phage epitopes appear to be proportional to the area of the phage surface accessible. Phage shells effectively protect nucleic acid-based drugs and, for the toxin construct, make cell-specific delivery systems with LD₅₀ values in culture sub-nanomolar. Conclusion: VLP technology has potential for therapeutic and prophylactic intervention in disease.

The induction of T-helper cell subsets during the course of blood stage Plasmodium chabaudi chabaudi infection was compared in immunologically intact NIH mice and mice that were depleted of B cells from birth by treatment with anti-mu antibodies. For intact mice, in which the acute primary parasitemia peaked 10 days following infection, purified splenic CD4+ T cells recovered during the ascending parasitemia produced high levels in vitro of interleukin 2 (IL-2) (peak levels on day 10) and gamma interferon (IFN-gamma) (peak levels on day 7). Sera collected from these mice at around this time contained relatively high levels of P. c. chabaudi-specific immunoglobulin 2a (peak levels on day 12), and serum nitric oxide activity was significantly elevated at peak parasitemia. During the descending primary parasitemia, production of IFN-gamma and IL-2 decreased, while levels of IL-4 and IL-10 produced by splenic CD4+ T cells were significantly raised from the time at which subpatency was recorded (day 17) and persisted for at least 50 days. This was concomitant with a significant increase in levels of parasite-specific immunoglobulin G1, which peaked at around the time of recrudescence. Thus, in normal mice, sequential appearance of Th1 and Th2 responses was observed. In contrast, in B-cell-depleted mice, recovery from acute primary parasitemia was followed by a persistent patent infection which did not drop below 0.1% for at least 75 days after initiation of infection. These mice were unable to mount a significant Th2 response, manifest as an enduring inability of splenic CD4+ T cells to produce significant levels of IL-4 and IL-10. IL-2 and IFN-gamma levels remained significantly elevated throughout the 50-day observation period, and there was sustained production of nitric oxide. These data show that immune responses mediated by CD4+ T cells of the Th1 subset are capable of limiting infection beyond the initial acute phase, but that they do not eliminate parasitemia. Furthermore, as the progression from a Th1-regulated to a Th2-regulated immune response fails to occur in B-cell-depleted mice, the data suggest that B cells are required for the downregulation of Th1-mediated and/or the generation of Th2-mediated protective immunity to P. c. chabaudi.

From regional and rural grassroots to a nationwide level, Vietnam has established a four-tiered hierarchical healthcare system, comprising national, provincial, district, and commune healthcare centers. Over the last three decades, alongside increasing provision of universal health insurance coverage and cutting healthcare expenditure, the country has demonstrated its dedication to preventative medicine and health promotion. Recent investment in research, development, and production has led to “homegrown” vaccines for SARS-CoV-2 now undergoing clinical trial. Nevertheless, despite substantial progress in improving health outcomes for the entire population, the healthcare sector experiences significant challenges. The current public system is paper-based, requires digitalization, and lacks information technology support. In common with many other countries, there is a vast disparity in the distribution of healthcare professionals between cities and rural areas, as well as between private and public sectors. Consequently, public healthcare in remote locations is particularly underserved. Moreover, ongoing underfunding caused by high out-of-pocket expenses for the average salary, as well as stigmatization of sensitive health issues by a largely conservative populace, demand a well-articulated and culturally sensitive approach. As the level of smartphone ownership and internet coverage are both comparatively high for Southeast Asia, the introduction of telemedicine, mobile health applications, and other digital health solutions may be both practicable and beneficial. Importantly, in order to develop healthcare facilities and reduce patient direct payments, the key issue of funding must be addressed. In order to overcome disease-related stigma, a locally tailored program of community education, awareness, and engagement is required. In summary, in several ways, Vietnam provides a role model for developing healthcare systems in low- and middle-income countries. There are undoubted hurdles to overcome, but the country continues to construct a healthcare system that is accessible and affordable for the majority.