Challenges of Developing Novel Vaccines With Particular Global Health Importance

Abstract

Six of the top ten leading causes of death in low resource settings could potentially be prevented by vaccination. Development of vaccines for individuals in these populations is difficult because of the biological complexity of the prevalent pathogens and the challenges inherent to development of any vaccine. This review discusses those challenges and promising advances to address them and highlights recent progress in development of vaccines against several pathogens of interest.

Keywords: HIV/AIDS; infectious diseases; low resource areas; malaria; respiratory syncytial virus; shigella; tuberculosis; vaccine development.

Figure 1

Steps in vaccine development. Mfg, manufacturing; Reg, regulatory; LCM, life cycle management.

Figure 2

Global Pipeline, TB Vaccines for Adolescents & Adults (October 2019). SSI, Statens Serum Institut; TBVI, TuBerculosis Vaccine Initiative; ChadOx1/MVA, Chimpanzee Adenovirus, Oxford University #1 and Modified Vaccinia virus Ankara; PPE, family of Mtb genes; CMV-6Ag, cytomegalovirus vector expressing six Mtb antigens; OHSU, Oregon Health & Sciences University; CysVac2/Ad, Mtb fusion protein with novel adjuvant; ZMP, zinc metalloprotease deletion mutant; Ad5 Ag85A, human type 5 adenovirus vector expressing antigen 85A; GamTBVac, two Mtb fusion proteins with a novel adjuvant; MTBVAC, rationally attenuated Mtb clinical isolate; TB/Flu04L, live recombinant influenza vectored TB vaccine; BCG, Bacille Calmette-Guerin; IAVI, International AIDS Vaccine Initiative; ID93/GLA-SE, recombinant fusion protein in a lucopyranosyl lipid A stable emulsion; IDRI, Infectious Disease Research Institute; WT, Wellcome Trust; M72/AS01, recombinant fusion protein combined with the AS01 adjuvant system; GSK, GlaxoSmithKline; DAR-901, inactivated M. obuense; H56:IC31, recombinant fusion protein in a novel adjuvant; VPM1002, recombinant BCG; SII, Serum Institute of India; VPM, Vakzine Projekt Management GmbH; MIP, M. indicus pranii. Reprinted with permission from TuBerculosis Vaccine Initiative (12).

Figure 3

Plasmodium life cycle. The inner circle highlights key stages of the parasite life cycle targeted by malaria vaccines under development. Stages in italics represent biological bottlenecks where relatively few parasites (< 100) must be targeted to break the life cycle. (For comparison, the total number of merozoites/schizonts in the human host can exceed 10¹²). The outer circle shows the major classes of malaria vaccines under development Reprinted with permission from Elsevier: Ballou and Vekemans (20).

Figure 4

Global malaria vaccine pipeline (July 2017). ChAd63/MVA, Chimpanzee Adenovirus 63 and Modified Vaccinia Virus Ankara; ME-TRAP, fusion protein of a Multi-Epitope string followed by the pre-erythrocytic Thrombospondin Related Adhesion Protein; Matrix M™, proprietary adjuvant; PfCelTOS FMP012, Plasmodium falciparum Cell-Traversal Protein for Ookinetes and Sporozoites and Falciparum Malaria Protein 12; PfPEBS, P. falciparum Pre-Erythrocytic and Blood Stage; PvDBP, P. vivax Duffy-Binding Protein; Pfs25-VLP, P. falciparum surface protein 25 Virus-Like Particle; RTS,S-AS01, Circumsporozoite protein fused to hepatitis B surface antigen in propriety adjuvant; MSP 1, Malaria Surface Protein 1; AMA1, Apical Membrane Antigen 1; FMP2.1/AS01B, protein based on AMA1 in proprietary adjuvant; Pfs25-EPA, P. falciparum surface protein 25 conjugated to Pseudomonas aeruginosa ExoProtein A; AMA1-DiCo, AMA1 Diversity Covering; P27A, unstructured synthetic peptide from P. falciparum trophozoite exported protein 1; PfsSPZ, radiation-attenuated whole organism P. falciparum sporozoite. Adapted from the World Health Organization (28).