An ideal malaria vaccine platform should potently induce protective immune responses and block parasite transmission from mosquito to human, and it should maintain these effects for an extended period. Here, we have focused on vaccine development based on adeno-associated virus serotype 1 (AAV1), a viral vector widely studied in the field of clinical gene therapy that is able to induce long-term transgene expression without causing toxicity
in vivo
. Our results show the potential utility of AAV1 vectors as an extremely potent booster vaccine to induce durable immunity when combined with an adenovirus-priming vaccine in a rodent malaria model. We generated a series of recombinant AAV1s and human adenovirus type 5 (AdHu5) expressing either
Plasmodium falciparum
circumsporozoite protein (PfCSP) or P25 (Pfs25) protein. Heterologous two-dose immunization with an AdHu5-prime and AAV1-boost (AdHu5-AAV1) elicited robust and durable PfCSP- or Pfs25-specific functional antibodies over 280 days. Regarding protective efficacy, AdHu5-AAV1 PfCSP achieved high sterile protection (up to 80% protection rate) against challenge with transgenic
Plasmodium berghei
sporozoites expressing PfCSP. When examining transmission-blocking (TB) efficacy, we found that immunization with AdHu5-AAV1 Pfs25 maintained TB activity
in vivo
against transgenic
P. berghei
expressing Pfs25 for 287 days (99% reduction in oocyst intensity, 85% reduction in oocyst prevalence). Our data indicate that AAV1-based malaria vaccines can confer potent and durable protection as well as TB efficacy when administered following an AdHu5 priming vaccine, supporting the further evaluation of this regimen in clinical trials as a next-generation malaria vaccine platform.
Rainfall trend analysis provides useful information for effective planning, and management of water resources, and gives an insight into climate change of a region. This study investigates trends in annual and seasonal rainfall over Sri Lanka using an Innovative Trend Analysis (ITA) and Mann–Kendall (MK) test with Sen's slope estimator. The MK test showed increasing trends in annual rainfall at 24 stations (65%) with five stations showing significant increasing trend. Annual rainfall at 13 locations (35%) showed decreasing trend, but none were significant (p < .05). ITA results for annual rainfall showed increasing trend at 67% stations while 33% stations showed decreasing trend. MK test results for seasonal rainfall indicated increasing trend at 76, 51, 32, and 86% of stations during First Inter‐Monsoon (FIM), Second Inter‐Monsoon (SIM), South West Monsoon (SWM), and North East Monsoon (NEM) seasons, respectively. Seasonal analysis of rainfall trend using ITA method showed increasing trend in 81, 70, 32, and 65% stations during FIM, SIM, SWM, and NEM, respectively. ITA and MK tests exhibited similar trend results for 80% of the stations. Moreover, Spearman's rho correlation coefficient between ITA and MK test trends showed significant (p < .05) positive correlation. In general, eastern, south eastern, north and north central regions of the country showed increasing rainfall trend over the last 31 years (1987–2017) while western, part of north western and central part of the country indicated a decreasing rainfall trend during the same period.
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