United States Patent:  6,004,802

Assignee:  University of Alabama at Birmingham (Birmingham, AL)

Filed:   May 30, 1996

Oral or peroral administration, including intragastrically, of killed whole pneumococci, lysate of pneumococci and isolated and purified PspA, as well as immunogenic fragments thereof, particularly when administered with an adjuvant such as cholera toxin provides protection in a host, animal or human, against pneumococcal infection, including colonization, and systemic infection, such as sepsis. The ability to elicit protection against pneumococcal colonization in a host prevents carriage among immunized individuals, which can lead to elimination of disease from the population as a whole.

SUMMARY OF THE INVENTION

In accordance with the present invention, it has now been surprisingly found that oral or peroral administration, preferably into the gut (e.g., stomach, intestines, digestive tract; intragastric), of pneumococcal surface protein A (PspA) or an immunogenic fragment thereof elicits an immunological response and can even provide protection to a host against pneumococcal infection such as colonization and/or systemic infection.

Accordingly, in one aspect, the present invention provides a method of protecting a host, preferably a human host, against pneumococci and/or systemic infection by oral or peroral administration to the host, preferably by administration into the gut (stomach, intestines, digestive tract; e.g., intragastrically) of the host, of an effective amount of at least one pneumococcal surface protein A (PspA) and/or an immunogenic fragment thereof containing at least one protection-eliciting epitope.

In another aspect, the present invention provides a method of eliciting an immunological response in a host against pneumococci and/or systemic infection by oral or peroral administration to the host, preferably administration into the gut (stomach, intestines, digestic tract; e.g., intragastrically) of the host, of an effective amount of at least one PspA and/or an immunogenic fragment thereof containing at least one epitope. More preferably, the response is protective and the epitope is protection-eliciting.

The PspA may be in the form of killed whole S. pneumoniae or a lysate of whole S. pneumoniae. Alternatively, the PspA may be in the form of purified isolated protein or a fragment thereof (individually and/or collectively, for purposes only of shorthand in this specification, "PspA") may be obtained from bacterial isolates or may be formed recombinantly. The PspA can be from in vivo expression thereof by a suitable vector containing DNA coding for PspA by recombinant techniques. The PspA is preferably in a vaccine or immunogenic composition. Such a composition can include a pharmaceutically acceptable adjuvant and/or a pharmaceutically acceptable carrier.

The PspA may be mixed with pharmaceutically acceptable excipients which are compatible with the PspA. Such excipients may include water, saline, dextrose, glycerol, ethanol, and combinations thereof. The immunogenic compositions and vaccines may further contain auxiliary substances, such as wetting or emulsifying agents, pH buffering agents, or adjuvants to enhance the effectiveness thereof.

In a preferred aspect of the invention, the PspA is administered with non-toxic amounts of cholera toxin as an adjuvant.

The oral administration preferably is effected by delivery into the stomach or gut, i.e., intragastrically to provide protection to the host against infection, preferably colonization, and more preferably against systemic infection. The oral administration also can provide protection to the host against pulmonary infection as well as protection to the host against an infection starting as a pulmonary infection. However, the oral administration can also involve respiratory mucosa, gingival mucosa or alveolar mucosa, and the administration can be perlingual or sublingual or into the mouth or respiratory tract, especially if the composition is administered in a liquid form, e.g., as a syrup, elixir etc. However, intragastric administration is preferred.

Thus, compositions of the invention especially for oral administration, are conveniently provided as liquid preparations, e.g., isotonic aqueous solutions, suspensions, emulsions, or viscous compositions which may be buffered to a select pH. However, since delivery to the digestive tract is preferred, compositions of the invention can be "solid" from the pills, tablets, capsules, caplets, and the like, including "solid" preparations which are time-release or which have a liquid filling, e.g., gelatin covered liquid, whereby the gelatin is dissolved in the stomach and/or small intestine for delivery into the gut and/or digestive system.

In a particular aspect of the invention, there is provided a method of immunization of a host against Streptococcus pneumoniae which comprises orally or perorally administering to the host an immunizing amount of pneumococcal surface protein A (PspA) in the form of a killed whole pneumococci, a lysate of pneumococci or an isolated PspA or an immunogenic fragment thereof.

The present invention further provides a vaccine composition or immunogenic composition for oral or peroral administration to a host, preferably for administration into the gut (stomach, digestive tract; e.g., intragastrically) of a host to confer protection or elicit an immunological response, against S. pneumoniae, which comprises:

an effective amount of a pneumococcal surface protein A (PspA) in the form of a killed whole pneumococci, a pneumococcal lysate, an isolated and purified PspA or an immunogenic fragment thereof containing at least one epitope, preferably protection-eliciting epitope, and optionally

an adjuvanting amount of an adjuvant, preferably CT, and optionally

a pharmaceutical carrier therefor.

Moreover, the present invention provides a compartmentalized kit comprising PspA or a fragment thereof, and a suitable carrier, diluent or excipient; and optionally, a pharmaceutically acceptable adjuvant; and further optionally, instructions for admixture and/or administration.

Claim 1 of 10 Claims

1. A method of immunization of a host against pneumococcal infection, which comprises orally administering to the host an immunizing amount of a composition comprising a pneumococcal component wherein said pneumococcal component consists essentially of isolated pneumococcal surface protein A (PspA) or at least one isolated fragment of such PspA containing at least one protection-eliciting epitope.

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