Scroll through the 5 CERID publications from CERID labs, PIs, and lab technicians publications that have hit the PubMed stands since the end of September! The scope of the individual publications is wide, covering a number of important bacteria and parasites from Mycobacterium tuberculosis to Plasmodium falciparum. Read on for highlights from the abstract and the diseases studied in this month’s publication round up by following the links! Publications are listed by the date published. All descriptions of the work have been paraphrased from the publications' respective abstracts and are cited as such.
Single-cell responses in HLA-B*57:01 abacavir patch test positive skin remote to the acute hypersensitivity reaction demonstrate polyclonal T-cell activation and proliferation characterized by a transcriptional and cellular response consistent with memory responses to altered peptides. Read the article here!
DNA vaccines have been licensed in veterinary medicine and have promise for humans. This format is relatively immunogenic in mice and guinea pigs, the two principle HSV-2 animal models, permitting rapid assessment of vectors, antigens, adjuvants, and delivery systems. Limitations include the relatively poor immunogenicity of naked DNA in humans and the profound differences in HSV-2 pathogenesis between host species. Herein, we detail lessons learned investigating candidate DNA vaccines in the progesterone-primed female mouse vaginal model of HSV-2 infection as a guide to investigators in the field. Read the full chapter here!
Chemoprophylaxis vaccination with sporozoites (CVac) with chloroquine induces protection against homologous P. falciparum sporozoite (PfSPZ) challenge, but whether blood-stage parasite exposure is required for protection remains unclear. Chloroquine suppresses and clears blood-stage parasitemia, while other antimalarial drugs such as primaquine act against liver-stage parasites. Here, we evaluate CVac regimens using chloroquine or primaquine as the partner drug to discern whether blood stage parasite exposure impacts protection against homologous controlled human malaria infection. In a phase 1, randomized, partial double-blind, placebo-controlled study of 36 malaria-naïve adults, all CVac subjects received chloroquine prophylaxis and bites from 12-15 P. falciparum-infected mosquitoes (CVac-chloroquine arm) at 3 monthly iterations, and some received post-exposure primaquine (CVac-primaquine/chloroquine arm). Drug control subjects received primaquine, chloroquine, and uninfected mosquito bites. After chloroquine washout, subjects, including treatment-naïve infectivity controls, underwent homologous PfSPZ controlled human malaria infection and were monitored for parasitemia for 21 days. No serious adverse events occurred. During CVac, all but one subject in the study remained blood smear-negative while only one subject (primaquine/chloroquine arm) remained PCR-negative. Upon challenge, compared to infectivity controls, 3/3 chloroquine arm subjects displayed delayed patent parasitemia (p=0.01) but not sterile protection, while 3/11 primaquine/chloroquine subjects remained blood smear negative. CVac-primaquine/chloroquine is safe and induces sterile immunity to P. falciparum in some recipients, but a single 45 mg dose of primaquine post-exposure does not completely prevent blood-stage parasitemia. Unlike previous studies, CVac-chloroquine did not produce sterile immunity. Read the full report here!
Read the full letter to the editor here!
Novel antimicrobials for treatment of Mycobacterium tuberculosis (Mtb) are needed. We hypothesized that nicotinamide (NAM) and nicotinic acid (NA) modulate macrophage function to restrict Mtb replication in addition to their direct antimicrobial properties. Both compounds had modest activity in 7H9 broth, but only NAM inhibited replication in macrophages. Surprisingly, in macrophages NAM and the related compound pyrazinamide (PZA) restricted growth of BCG but not wild-type M.bovis, which both lack a functional PncA amidase rendering each strain resistant to these drugs in broth culture. Interestingly, NAM was not active in macrophages infected with a virulent Mtb mutant encoding a deletion in pncA. We conclude that the differential activity of NAM and NA on infected macrophages suggests host-specific NAM targets that are associated with M. bovis strain virulence rather than PncA-dependent direct antimicrobial properties. These activities are sufficient to restrict attenuated BCG, but not virulent wild-type M. bovis or Mtb. Read the full paper here!