To date, limited genetic changes in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome have been described. Here, we report a 382-nucleotide (nt) deletion in SARS-CoV-2 that truncates open reading frame 7b (ORF7b) and ORF8, removing the ORF8 transcription regulatory sequence (TRS) and eliminating ORF8 transcription. The earliest 382-nt deletion variant was detected in Singapore on 29 January 2020, with the deletion viruses circulating in the country and accounting for 23.6% (45/191) of SARS-CoV-2 samples screened in this study. SARS-CoV-2 with the same deletion has since been detected in Taiwan, and other ORF7b/8 deletions of various lengths, ranging from 62 nt to 345 nt, have been observed in other geographic locations, including Australia, Bangladesh, and Spain. Mutations or deletions in ORF8 of SARS-CoV have been associated with reduced replicative fitness and virus attenuation. In contrast, the SARS-CoV-2 382-nt deletion viruses showed significantly higher replicative fitness in vitro than the wild type, while no difference was observed in patient viral load, indicating that the deletion variant viruses retained their replicative fitness. A robust antibody response to ORF8 has been observed in SARS-CoV-2 infection, suggesting that the emergence of ORF8 deletions may be due to immune-driven selection and that further deletion variants may emerge during the sustained transmission of SARS-CoV-2 in humans. IMPORTANCE During the SARS epidemic in 2003/2004, a number of deletions were observed in ORF8 of SARS-CoV, and eventually deletion variants became predominant, leading to the hypothesis that ORF8 was an evolutionary hot spot for adaptation of SARS-CoV to humans. However, due to the successful control of the SARS epidemic, the importance of these deletions for the epidemiological fitness of SARS-CoV in humans could not be established. The emergence of multiple SARS-CoV-2 strains with ORF8 deletions, combined with evidence of a robust immune response to ORF8, suggests that the lack of ORF8 may assist with host immune evasion. In addition to providing a key insight into the evolutionary behavior of SARS-CoV-2 as the virus adapts to its new human hosts, the emergence of ORF8 deletion variants may also impact vaccination strategies.

The origin of Plasmodium falciparum, the etiological agent of the most dangerous forms of human malaria, remains controversial. Although investigations of homologous parasites in African Apes are crucial to resolve this issue, studies have been restricted to a chimpanzee parasite related to P. falciparum, P. reichenowi, for which a single isolate was available until very recently. Using PCR amplification, we detected Plasmodium parasites in blood samples from 18 of 91 individuals of the genus Pan, including six chimpanzees (three Pan troglodytes troglodytes, three Pan t. schweinfurthii) and twelve bonobos (Pan paniscus). We obtained sequences of the parasites' mitochondrial genomes and/or from two nuclear genes from 14 samples. In addition to P. reichenowi, three other hitherto unknown lineages were found in the chimpanzees. One is related to P. vivax and two to P. falciparum that are likely to belong to distinct species. In the bonobos we found P. falciparum parasites whose mitochondrial genomes indicated that they were distinct from those present in humans, and another parasite lineage related to P. malariae. Phylogenetic analyses based on this diverse set of Plasmodium parasites in African Apes shed new light on the evolutionary history of P. falciparum. The data suggested that P. falciparum did not originate from P. reichenowi of chimpanzees (Pan troglodytes), but rather evolved in bonobos (Pan paniscus), from which it subsequently colonized humans by a host-switch. Finally, our data and that of others indicated that chimpanzees and bonobos maintain malaria parasites, to which humans are susceptible, a factor of some relevance to the renewed efforts to eradicate malaria. Chimpanzees and gorillas are known to have malaria parasites (genus Plasmodium) similar to those that infect humans. It is likely that detailed molecular studies of these parasites will help understand important aspects of the malaria disease and of immune defences in humans, and could then guide the development of novel control measures. However, few studies of parasites in African Apes have been conducted to date. Here we present the results of a survey of malaria parasites in chimpanzees and bonobos, our closest relatives. In chimpanzees, we identified two new parasite species closely related to P. falciparum, the most dangerous of the parasites in humans. We also found that bonobos harbour malaria parasites including P. falciparum. Phylogenetic analyses of these parasites strongly suggested that P. falciparum evolved in bonobos, and that it was introduced into humans from bonobos at a later date. Overall, our findings have substantially altered our perception of the origin of malaria parasites in humans.

The genetic basis of a host's resistance to parasites has important epidemiological and evolutionary consequences. Understanding this genetic basis can be complicated by non-genetic factors, such as environmental quality, which may influence the expression of genetic resistance and profoundly alter patterns of disease and the host's response to selection. In particular, understanding the environmental influence on the genetic resistance of mosquitoes to malaria gives valuable knowledge concerning the use of malaria-resistant transgenic mosquitoes as a measure of malaria control. We made a step towards this understanding by challenging eight isofemale lines of the malaria vector Anopheles stephensi with the rodent malaria parasite Plasmodium yoelii yoelii and by feeding the mosquitoes with different concentrations of glucose. The isofemale lines differed in infection loads (the numbers of oocysts), corroborating earlier studies showing a genetic basis of resistance. In contrast, the proportion of infected mosquitoes did not differ among lines, suggesting that the genetic component underlying infection load differs from the genetic component underlying infection rate. In addition, the mean infection load and, in particular, its heritable variation in mosquitoes depended on the concentration of glucose, which suggests that the environment affects the expression and the evolution of the mosquitoes' resistance in nature. We found no evidence of genotype-by-environment interactions, i.e. the lines responded similarly to environmental variation. Overall, these results indicate that environmental variation can significantly reduce the importance of genes in determining the resistance of mosquitoes to malaria infection.

Research aimed at developing vaccines against infectious diseases generally seeks to induce robust immune responses to immunodominant antigens. This approach has led to a number of efficient bacterial and viral vaccines, but it has yet to do so for parasitic pathogens. For malaria, a disease of global importance due to infection by Plasmodium protozoa, immunization with radiation-attenuated sporozoites uniquely leads to long lasting sterile immunity against infection. The circumsporozoite protein (CSP), an important component of the sporozoite's surface, remains the leading candidate antigen for vaccines targeting the parasite's pre-erythrocytic stages. Difficulties in developing CSP-based vaccines that reproduce the levels of protection afforded by radiation-attenuated sporozoites have led us to question the role of CSP in the acquisition of sterile immunity. We have used a parasite transgenic for the CSP because it allowed us to test whether a major immunodominant Plasmodium antigen is indeed needed for the induction of sterile protective immunity against infection. We employed a P. berghei parasite line that expresses a heterologous CSP from P. falciparum in order to assess the role of the CSP in the protection conferred by vaccination with radiation-attenuated P. berghei parasites. Our data demonstrated that sterile immunity could be obtained despite the absence of immune responses specific to the CSP expressed by the parasite used for challenge. We conclude that other pre-erythrocytic parasite antigens, possibly hitherto uncharacterised, can be targeted to induce sterile immunity against malaria. From a broader perspective, our results raise the question as to whether immunodominant parasite antigens should be the favoured targets for vaccine development.

Understanding the impact of age on vaccinations is essential for the design and delivery of vaccines against SARS-CoV-2. Here, we present findings from a comprehensive analysis of multiple compartments of the memory immune response in 312 individuals vaccinated with the BNT162b2 SARS-CoV-2 mRNA vaccine. Two vaccine doses induce high antibody and T cell responses in most individuals. However, antibody recognition of the Spike protein of the Delta and Omicron variants is less efficient than that of the ancestral Wuhan strain. Age-stratified analyses identify a group of low antibody responders where individuals ≥60 years are overrepresented. Waning of the antibody and cellular responses is observed in 30% of the vaccinees after 6 months. However, age does not influence the waning of these responses. Taken together, while individuals ≥60 years old take longer to acquire vaccine-induced immunity, they develop more sustained acquired immunity at 6 months post-vaccination. A third dose strongly boosts the low antibody responses in the older individuals against the ancestral Wuhan strain, Delta and Omicron variants.

Life cycles and molecular data for terrestrial haemogregarines are reviewed in this article. Collection material was re-examined: Hepatozoon argantis Garnham, 1954 in Argas brumpti was reassigned to Hemolivia as Hemolivia argantis (Garnham, 1954) n. comb.; parasite DNA was extracted from a tick crush on smear of an archived slide of Hemolivia stellata in Amblyomma rotondatum, then the 18S ssrRNA gene was amplified by PCR. A systematic revision of the group is proposed, based on biological life cycles and phylogenetic reconstruction. Four types of life cycles, based on parasite vector, vertebrate host and the characteristics of their development, are defined. We propose combining species, based on their biology, into four groups (types I, II, III and IV). The characters of each type are defined and associated with a type genus and a type species. The biological characters of each type are associated with a different genus and a type species. The phylogenetic reconstruction with sequences deposited in the databases and our own new sequence of Hemolivia stellata is consistent with this classification. The classification is as follows: Type I, Hepatozoon Miller, 1908, type species H. perniciosum Miller, 1908; Type II, Karyolysus Labbé, 1894, type species K. lacertae (Danilewsky, 1886) Reichenow, 1913; Type III Hemolivia Petit et al., 1990, type species H. stellata, Petit et al., 1990; and Type IV: Bartazoon n. g., type species B. breinli (Mackerras, 1960). Une revue des cycles biologiques et des données moléculaires concernant les Hémogrégarines terrestres est effectuée. Du matériel de collection a été réexaminé : Hepatozoon argantis Garnham, 1954 chez Argas brumpti est reclassé dans Hemolivia comme Hemolivia argantis (Garnham, 1954) n. comb ; de l’ADN a été extrait d’un écrasement de tique sur lame, provenant d’une partie du matériel type d’Hemolivia stellata chez Amblyoma rotondatum, puis le gène 18S ssrRNA a été amplifié par PCR. Une révision systématique du groupe, basée sur les cycles biologiques et sur les reconstructions phylogénétiques est proposée. Quatre types de cycles biologiques sont définis, en fonction du vecteur, de l’hôte vertébré, des parasites et des caractéristiques de leurs développements. Nous proposons de rassembler les espèces en fonction de leur biologie en quatre groupes (types I, II, III, IV). Les caractères de chaque type sont définis et associés à un genre et à une espèce type. La reconstruction phylogénique faite à partir de séquences déposées dans les banques de données et notre nouvelle séquence d’Hemolivia stellata est compatible avec cette nouvelle classification. La classification est la suivante : Type I, Hepatozoon Miller, 1908, avec espèce-type H. perniciosum Miller, 1908 ; Type II, Karyolysus Labbé, 1894, avec espèce-type K. lacertae (Danilewsky, 1886) Reichenow, 1913 ; Type III Hemolivia Petit et al., 1990, avec espèce-type H. stellata, Petit et al., 1990 ; Type IV : Bartazoon n. g., avec espèce-type B. breinli (Mackerras, 1960) n. comb.