Trachoma vaccine field trials in The Gambia

Abstract

SUMMARYThe ability of two live trachoma vaccines to protect against naturally acquired infection was tested in young Gambian children. With a mineral oil adjuvant vaccine prepared from a Gambian strain of trachoma (MRC–187) a barely significant measure of protection was demonstrable 6 months after the first dose, but not at 1 year, despite a reinforcing dose given 6 months after the first. In a later trial an aqueous vaccine prepared from the ‘fast-killing’ variants of strains ‘SA–2’ and ‘ASGH’ failed to induce immunity. Two years after vaccination, the proportion of vaccinated children progressing to cicatricial trachoma was less than in the controls, and the average severity of the disease in terms of clinical score was greater; vaccine-induced hypersensitivity may have contributed to this result.Irrespective of whether they had received trachoma vaccine, children with completely normal eyes at the outset were less likely to acquire trachoma than those with slight conjunctival folliculosis or papillary hyperplasia. In children acquiring trachoma, there was a highly significant positive correlation between severity of the disease and the presence of conjunctival inclusions. The pattern of trachoma differed significantly in the two villages used in both trials; the prev alence, severity and proportion of inclusion-positive subjects were all higher in the village with the greater population density.An efficient follow-up organization, use of a slit-lamp for clinical observations, and a scoring system for recording physical signs are all desirable for trachoma vaccine field trials.We are highly indebted to Dr G. Turner (Lister Institute, Elstree, Herts) for his assistance in making the vaccine used for Trial II; to Dr N. M. Lam (Pfizer Ltd.) and Dr C. H. Smith (Evans Medical Ltd.) for making the Trial III vaccine; to Dr I. A. Sutherland (M.R.C. Statistical Unit) for his advice and help with the statistical aspects; to the Pennsylvania Refinery Co. Inc. for a generous gift of Drakeol 6 VR; and to Mr M. Race for his invaluable technical assistance in The Gambia. We are also grateful to the Director and staff of the M.R.C. Laboratories, The Gambia, for various facilities; and to The Gambian Government for per mission to undertake these trials.

Temporal Delay of Peak T-Cell Immunity DeterminesChlamydia pneumoniaePulmonary Disease in Mice

“…The clinical correlate to protective Th1 cells is a vigorous DTH reaction to chlamydial antigens (11,17,53,75). However, a pronounced hypersensitivity response after repeated infections also drives the progression of the pathological lesion in chlamydial diseases such as trachoma (60,64). This conundrum, i.e., the same type of immune reactivity to chlamydiae appears to be protective as well as pathological, has perplexed Chlamydia research for decades.…”

“…Repeated ocular challenge was required to produce the corneal pannus and conjunctival scarring characteristic of severe trachoma (20,64). Similarly, children receiving semipurified C. trachomatis vaccines exhibited vaccine-induced delayedtype hypersensitivity (DTH) responses and severe disease with higher clinical scores (60).…”

The serum and conjunctival antibody response to trachoma in Gambian children

“…In describing the criteria on which this classification was based (Sowa et al 1969) we mentioned that the diagnosis of trachoma was made in accordance with the recommendations of the WHO Expert Committee on Trachoma (1962); we also noted that children with a diagnosis of Ab were more likely to acquire classical trachoma than N children. This tendency was pronounced in the study described here; furthermore, all children diagnosed clinically as 'trachoma dubium' (Tr D) (i.e.…”

“…After preliminary work on immunofluorescence methods, a group of 99 infants was selected in Salekini, a large Gambian village with 3500 inhabitants (Sowa, Sowa, Collier & Blyth, 1969;Sowa et al 1971). Thirty-seven of these children had normal (N) eyes (Table 1); the remainder had early active trachoma with or without corneal lesions, or minor conjunctival abnormalities not suggestive of TRIC infection (Ab).…”

Studies on the Purification of Chlamydial Agents Grown in Yolk Sacs of Embryonated Eggs Using Disulphide-linked Immunosorbents and Enzymes

“…These include: centrifugation (Col6n & Moulder, 1958;Jenkin, 1960); centrifugation with prior treatment with I M-KCl (Taverne, Blyth & Reeve, 1964;Sowa et al 1969) or trypsin and celite (Weiss et ul. 1964); density gradient centrifugation as a main or terminal step (Tamura & Higashi, 1963;Vedros, 1967;Detels, Wang & Grayston, 1968: Sarov & Becker, 1968; DEAE-cellulose chromatography (Ormsbee & Weiss, 1963 ; Katzenelson & Bernkopf, 1965; Provost & Vickers, I 972) ; liquid-liquid partition using fluorocarbons (e.g.…”